Ethoxyethane (Diethyl ether; Et2O) by Asch

Query 1. Query

Query

Results

Date

RX.PXRN=1696894

630 reactions in Reaxys

2016-05-04 01h:47m:17s (EST)

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Rx-ID: 193868 View in Reaxys 1/630 Yield 99 %

Conditions & References Evaluation of Catalyst Properties A fixed bed gas flow catalytic reactor was used as a reactor. 3 ml of above prepared catalysts was filled in a stainless steel tube reactor with a diameter of 9.5 mm”. As a pretreatment, hydrogen reduction was conducted for 1 hour under a carrier gas atmosphere (10percent H2/N2 base; flow rate 125 ml/min) at 400° C. Afier the pretreatment, the testing was conducted at a temperature range of 250° C. to 400° C. and a pressure range of 0 to 51 bar, nitrogen flow rate at 125 sccm and ethanol flow rate at 0.2 ml/min. The reaction duration ranged from 5 to 80 hrs. With reduced Sn/hydrotalcite catalyst, T= 250 °C , p= 25502.6Torr , Catalytic behavior, Reagent/catalyst, Temperature, Pressure Patent; Celanese International Corporation; Zhang, Cheng; Johnston, Victor J.; US2014/275636; (2014); (A1) English View in Reaxys

2.6 %

2. Experimental General procedure: Catalytic experiments were performed at atmospheric pressure in a tubular flow reactor feeding 7.9percent v/v ethanol in nitrogen at 298 K (total flow rate of 80 cm3/min) as described in our previous studies With SA5, T= 199.84 °C , Inert atmosphere, Catalytic behavior, Reagent/catalyst, Temperature Phung, Thanh Khoa; Busca, Guido; Catalysis Communications; vol. 68; (2015); p. 110 - 115 View in Reaxys With sulfuric acid, T= 130 - 140 °C , Darstellung im grossen Gmelins,L.; View in Reaxys Boullay; ; vol. 44; (1813); p. 270 View in Reaxys Ullmann; View in Reaxys With acid-mud, T= 180 - 190 °C , im Autoklaven Patent; Pape &amp; Co.; DE679970; (1936); View in Reaxys With pumice stone, sulfuric acid, T= 135 °C Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 192; (1931); p. 1335 View in Reaxys With sodium chloride, Mechanismus van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 758,761 View in Reaxys With aluminum oxide, Abhaengigkeit der Ausbeute bei der Dehydratisierung vom Wassergehalt und von der Aktivitaet des verwendeten Al2O3 sowie von der Reaktionstemperatur Hori; Oike; Hukusima; Nippon Nogei Kagaku Kaishi; vol. 15; (1939); p. 483; ; (1940); p. 4725 View in Reaxys Alexander; Horn; Munro; Canadian Journal of Research, Section B: Chemical Sciences; vol. 15; (1937); p. 439ff; Chem. Zentralbl.; vol. 109; nb. I; (1938); p. 3327 View in Reaxys With Al2O3-containing alumcatalyst, T= 200 °C Patent; Crima S.A.; US2209699; (1937) View in Reaxys With Fuller's Earth, T= 150 - 200 °C

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Patent; Rheinische Kampfer-Fabr.; DE638756; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 23; p. 256 View in Reaxys Patent; Rheinische Kampfer-Fabr.; US1908190; (1928) View in Reaxys With aluminum oxide, sulfatecatalyst, T= 300 °C Patent; Crima S.A.; DE717202; (1934); View in Reaxys With Catalyst M-Chromium oxide, sulfatecatalyst, T= 300 °C Patent; Crima S.A.; DE717202; (1934); View in Reaxys With sulfuric acid, technische Darstellung Himmler; ; vol. 5; (1954); p. 778 - 780 View in Reaxys With sodium alum, technische Darstellung Himmler; ; vol. 5; (1954); p. 778 - 780 View in Reaxys With sulfuric acid, benzene, T= 115 - 120 °C , wird das Wasser als azeotropes Gemisch mit Benzol entfernt Patent; Usines de Melle; DE527941; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 16; p. 2985 View in Reaxys With anhydrous aluminium sulphate, sulfuric acid, T= 140 °C Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 151; (1910); p. 394; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;9; (1911); p. 373 View in Reaxys Senderens; Annales de Chimie (Cachan, France); vol. &lt;9&gt;18; (1922); p. 126 View in Reaxys Moser; Lindinger; Monatshefte fuer Chemie; vol. 44; (1923); p. 142 View in Reaxys With lead sulphate, sulfuric acid, T= 140 °C Senderens; Annales de Chimie (Cachan, France); vol. &lt;9&gt;18; (1922); p. 126 View in Reaxys With lead sulphate, sulfuric acid, T= 125 - 130 °C Senderens bei V.Grignard; View in Reaxys Schlatter; ; vol. 12; (1920); p. 1101; Chem. Zentralbl.; vol. 92; nb. I; (1921); p. 349 View in Reaxys With aluminum oxide, T= 240 - 300 °C Jatkar; Watson; Journal of the Indian Institute of Science, Section A; vol. 9; p. 74; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 2766 View in Reaxys With aluminum oxide, T= 275 °C Pease; Yung; Journal of the American Chemical Society; vol. 46; (1924); p. 395 View in Reaxys Senderens; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 35; (1924); p. 1144 View in Reaxys With aluminum oxide, T= 269 °C Alvarado; Journal of the American Chemical Society; vol. 50; (1928); p. 791

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View in Reaxys With aluminum oxide, T= 300 °C Alvarado; Journal of the American Chemical Society; vol. 50; (1928); p. 791 View in Reaxys Pease; Yung; Journal of the American Chemical Society; vol. 46; (1924); p. 395 View in Reaxys Senderens; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 35; (1924); p. 1144 View in Reaxys With anhydrous aluminium sulphate, T= 220 - 235 °C , unter verschiedenen Bedingungen Jatkar; Watson; Journal of the Indian Institute of Science, Section A; vol. 9; p. 77; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 2766 View in Reaxys With chromium(III) potassium sulfate, T= 265 - 295 °C , unter verschiedenen Bedingungen Jatkar; Watson; Journal of the Indian Institute of Science, Section A; vol. 9; p. 77; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 2766 View in Reaxys With potassium alum, T= 200 - 270 °C , unter verschiedenen Bedingungen Jatkar; Watson; Journal of the Indian Institute of Science, Section A; vol. 9; p. 77; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 2766 View in Reaxys With air, T= 150 - 250 °C , Ueberleiten ueber japanische saure Erde Inoue; Bulletin of the Chemical Society of Japan; vol. 1; (1926); p. 198; Chem. Zentralbl.; vol. 98; nb. I; (1927); p. 9 View in Reaxys With carbon dioxide, T= 150 - 250 °C , Ueberleiten ueber japanische saure Erde Inoue; Bulletin of the Chemical Society of Japan; vol. 1; (1926); p. 198; Chem. Zentralbl.; vol. 98; nb. I; (1927); p. 9 View in Reaxys With sulfuric acid, Anlage zur technischen Darstellung auf Kuba Humboldt; ; vol. 33; p. 335; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 850 View in Reaxys With aluminum oxide, T= 335 °C , p= 14710.2Torr Hayashi; Nippon Kagaku Zasshi; vol. 78; (1957); p. 222,225; ; (1957); p. 6339 View in Reaxys With phosphoric acid Boullay; ; vol. 44; (1813); p. 270 View in Reaxys With orthoarsenic acid Boullay; Annales de Chimie (Cachan, France); vol. &lt;1&gt; 78; (1811); p. 284 View in Reaxys With hydrochlorid acid, T= 100 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 390 View in Reaxys With hydrogen bromide, T= 100 °C Villiers; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 136; (1903); p. 1551; Annales de Chimie (Cachan, France); vol. &lt;7&gt; 29; (1903); p. 565

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View in Reaxys With hydrogen iodide, T= 100 °C , die Menge des enstehenden Aethers waechst mit der Temp. Villiers; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 136; (1903); p. 1551; Annales de Chimie (Cachan, France); vol. &lt;7&gt; 29; (1903); p. 565 View in Reaxys With metal chloride Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With metal sulfate Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With manganese (II) chloride, T= 240 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With iron(II) chloride, T= 240 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With chromium(III) potassium sulfate, T= 200 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With zinc(II) chloride Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 311 View in Reaxys Masson; Justus Liebigs Annalen der Chemie; vol. 31; (1839); p. 63 View in Reaxys With CoCl2 Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108 View in Reaxys With cadmium (II) chloride Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108 View in Reaxys With tin(IV) chloride Kuhlmann; Justus Liebigs Annalen der Chemie; vol. 33; (1840); p. 97,192 View in Reaxys With copper(II) sulfate Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 311 View in Reaxys With stannous sulfate Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 311 View in Reaxys With ammonium chloride Berthelot; Justus Liebigs Annalen der Chemie; vol. 83; (1852); p. 110

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View in Reaxys With metal bromide Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108 View in Reaxys With metal iodide Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108 View in Reaxys With [14C]-Morphine hydrochloride Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 432 View in Reaxys With cinchonine; monohydrochloride Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 432 View in Reaxys With quinoline hydrochloride Van Hove; Chem. Zentralbl.; vol. 78; nb. I; (1907); p. 235 View in Reaxys With amine hydrochloride Swarts; Chem. Zentralbl.; vol. 75; nb. II; (1904); p. 1377 View in Reaxys Van Hove; Chem. Zentralbl.; vol. 80; nb. II; (1909); p. 1414 View in Reaxys With sulfuric acid, T= 140 - 145 °C , Oberhalb dieser Temperatur nimmt die Ausbeute ab; bei 160grad entweicht sehr viel SO2 Peter; Chemische Berichte; vol. 32; (1899); p. 1418 View in Reaxys Norton; Prescott; American Chemical Journal; vol. 6; (1884); p. 243 View in Reaxys With stannous sulfate, sulfuric acid Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 311 View in Reaxys With sodium alum, T= 200 °C Patent; Chem.Werke BYK; DE278777; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 32 View in Reaxys With sodium alum, T= 180 - 195 °C Mailhe; de Godon; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;25; (1919); p. 565 View in Reaxys With sulfuric acid, Geschwindigkeit Evans; Albertson; Journal of the American Chemical Society; vol. 39; (1917); p. 460 View in Reaxys With anhydrous aluminium sulphate, sulfuric acid, T= 120 °C Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 151; (1910); p. 394; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;9; (1911); p. 373 View in Reaxys With pyrophosphoric acid, Darstellung

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Patent; Hofmann; Josephy; DE292543 View in Reaxys With meta-phosphoric acid, Darstellung Patent; Hofmann; Josephy; DE292543 View in Reaxys With hydrochlorid acid, zinc(II) chloride, p= 1323.9Torr Patent; Wacker,A.; DE680328; (1934); View in Reaxys With active bauxit, T= 270 °C Heinemann; Wert; McCarter; Industrial and Engineering Chemistry; vol. 41; (1949); p. 2931 View in Reaxys With sulfuric acid, Petroleum ether, T= 105 °C , wird das Wasser als azeotropes Gemisch mit Benzin entfernt Patent; Usines de Melle; DE527941; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 16; p. 2985 View in Reaxys With aluminum oxide, T= 350 °C Boswell; Dilworth; Journal of Physical Chemistry; vol. 29; (1925); p. 1494 View in Reaxys Pease; Yung; Journal of the American Chemical Society; vol. 46; (1924); p. 395 View in Reaxys Senderens; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 35; (1924); p. 1144 View in Reaxys With kaolin Skaerblom; Svensk Kemisk Tidskrift; vol. 40; p. 123; Chem. Zentralbl.; vol. 99; nb. II; (1928); p. 182 View in Reaxys With sulfuric acid, T= 25 °C , die Grenze der Aetherbildung ist von der Temp. unabhaengig Villiers; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 136; (1903); p. 1452 View in Reaxys With uranyl sulphate, T= 240 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With manganese sulphate Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108 View in Reaxys With iron(III) chloride Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 311 View in Reaxys Kuhlmann; Justus Liebigs Annalen der Chemie; vol. 33; (1840); p. 97,192 View in Reaxys mit anderen Verbindungen der Nichtmetalle mit Halogen reagiert Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With benzenesulfonic acid, T= 134 - 135 °C Krafft; Chemische Berichte; vol. 26; (1893); p. 2833 View in Reaxys

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Patent; Krafft; Roos; DE69115; Fortschr. Teerfarbenfabr. Verw. Industriezweige; III, 11 View in Reaxys With aluminum oxide, T= 250 °C Clark; Graham; Winter; Journal of the American Chemical Society; vol. 47; (1925); p. 2753 View in Reaxys With aluminum oxide, T= 354 °C Alvarado; Journal of the American Chemical Society; vol. 50; (1928); p. 791 View in Reaxys With potassium alum, T= 225 °C Jatkar; Watson; Journal of the Society of Chemical Industry, London; vol. 45; (1926); p. 168T; Journal of the Indian Institute of Science, Section A; vol. 9; p. 93; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 1188,2766 View in Reaxys With sulfuric acid, T= 100 - 200 °C , bei allen Konzentrationen der Schwefelsaeure bis zu 0.5prozent herab Aetherbildung Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With tin(ll) chloride, T= 240 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 48; (1831); p. 427,450 View in Reaxys With iron(II) sulfate Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108 View in Reaxys With boron trifluoride Desfosses; Annales de Chimie (Cachan, France); vol. &lt;2&gt; 16; (1821); p. 72 View in Reaxys With hydrochloride certain alkaloids Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 432 View in Reaxys With sulfuric acid, iron(III) chloride Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 311 View in Reaxys With fired clay, T= 240 - 260 °C Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 228; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 5; (1909); p. 480 View in Reaxys With Al3+-montmorillonite, Time= 4h, T= 200 °C , Yield given Ballantine, James A.; Davies, Mary; Purnell, Howard; Rayanakorn, Mongkon; Thomas, John M.; Williams, Kevin J.; Journal of the Chemical Society, Chemical Communications; nb. 9; (1981); p. 427 - 428 View in Reaxys T= 135 °C , Leiten ueber mit H2SO4 getraenkten Bimsstein Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 192; (1931); p. 1335 View in Reaxys Pyrolysis

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Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 228; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 5; (1909); p. 480 View in Reaxys With monoaluminum phosphate, T= 299.9 °C , Rate constant, Thermodynamic data Campelo, J. M.; Garcia, A.; Herencia, J. F.; Luna, D.; Marinas, J. M.; Romero, A. A.; Journal of Catalysis; vol. 151; nb. 2; (1995); p. 307 - 314 View in Reaxys With sulfur hexafluoride anion, T= 24.84 °C , p= 50Torr , Kinetics, Further Variations: Pressures Viggiano; Fernandez, Abel I.; Troe; Physical Chemistry Chemical Physics; vol. 7; nb. 7; (2005); p. 1533 - 1539 View in Reaxys 6 :A reactor system was set up as described in Example 3 above, with the exception that two separate reactors (both 150.x.10 mm) packed with bare unmodified titania (80 μm diameter/60 Angstrom average pore diameter) (15.30 grams and 15.24 grams of titania). Etherification was then performed using the reactor system with ethanol as a feedstock. The ethanol feedstock was sparged with pure nitrogen.The reaction conditions for this example are summarized below in Table 7. TABLE 7 Inlet Reactor Reactor Temp. Outlet Temp. EtOH Inlet Outlet of heater of heater Front Back Flow Temp. Temp. exchange exchanger Pressure Pressure Rate (° C.) (° C.) (° C.) (° C.) (PSI) (PSI) (g/min) 375 350 221 72 2350 2350 0.744 375 352 222 76 2350 2350 0.744 375 354 222 81 2350 2350 0.744 The resulting gas was shown to be combustible by igniting the same and observing it to burn. The reaction products were identified using NIR and NMR analysis. The average mass balance (liquid in versus liquid out) of chemical reactions is shown below in Table 8. It was determined that 21.1 percent of the ethanol was converted to DEE on a mass in/mass out basis. TABLE 8 EtOH Water EtOH Flow Flow DEE and (g/min) at (g/min) Produced Organics Coldwell Inlet at Outlet (g/min) (g/min) (g/min) 0.744 0.48 0.16 0.11 0.0002 The data show that an alcohol feedstock including ethanol can be converted into an ether reaction product using a metal oxide catalyst. With Titanium(IV) oxide, T= 350 - 375 °C , p= 121533Torr , Gas phase, Conversion of starting material Patent; McNeff, Clayton V.; McNeff, Larry C.; Yan, Bingwen; US2008/319236; (2008); (A1) English View in Reaxys With glycerol, Time= 6h, T= 119.84 °C Pariente, Stephane; Tanchoux, Nathalie; Fajula, Franois; Green Chemistry; vol. 11; nb. 8; (2009); p. 1256 - 1261 View in Reaxys 50 %Chromat.

Example 6Quartz wool was packed on the bottom of a heat resistant glass reactor of an inner diameter of 10 mm, and a predetermined amount of the catalyst was charged thereon. A fine glass tube for inserting a thermoelectric couple was put in the center of the reaction tube to measure the temperature, and the height of the quartz wool was so adjusted that a tip of the thermoelectric couple was positioned at the center. The reaction apparatus was constituted by a mass flow controller, a micro feeder, a reaction tube and a gas chromatography (with a hydrogen flame detector) for analysis. The reaction gas was the one obtained by introducing the ethyl alcohol through the micro feeder into carrier gas of which the flow rate was controlled by the mass flow meter, and was introduced from above the catalyst layer so as to flow downward thereof to be brought to a gas sampler for gas chromatography. The reaction tube was heated by an electric furnace so that the catalyst layer assumed a predetermined temperature. Prior to the reaction, the catalyst was pre-treated by flowing nitrogen gas at a rate of 50 mL/min. at 673K for 2 hours. The reaction was conducted by feeding mixed gas (containing 5.5percent by volume of ethyl alcohol) of ethyl alcohol and nitrogen at a rate of 10 mL/min. The pressure was 0.1 MPa.Table 1 shows the results of the thus conducted reaction. In Table 1, "Butene" stands for a mixture of 1-butene and 2-butene, "Ethanol conversion (percent)" stands for a percentage of the mol number of ethyl alcohol that has reacted to the mol number of ethyl alcohol before reacted, and "Selectivity coefficient (percent)" stands for a percentage of the mol number of the component calculated as the ethyl alcohol to the mol number of the reacted ethyl alcohol. The same also holds true in Tables 2 to 5 appearing later. With Ni on C12-MCM-41, T= 199.84 °C , p= 750.075Torr , Gas phase, Inert atmosphere Patent; Iwamoto, Masakazu; Yamamoto, Takashi; Haishi, Teruki; US2010/168491; (2010); (A1) English View in Reaxys With copper nanoparticles on alumina support, T= 200 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys

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With aluminum oxide, oxygen, T= 200 °C Lippits; Nieuwenhuys; Journal of Catalysis; vol. 274; nb. 2; (2010); p. 142 - 149 View in Reaxys With cesium hydroxide monohydrate, tungsten hexachloride, acetic acid, Time= 20h, T= 200 °C , Equilibrium constant Guo, Chongshen; Yin, Shu; Zhang, Peilin; Yan, Mei; Adachi, Kenji; Chonan, Takeshi; Sato, Tsugio; Journal of Materials Chemistry; vol. 20; nb. 38; (2010); p. 8227 - 8229 View in Reaxys With cesium hydroxide monohydrate, tungsten hexachloride, Time= 20h, T= 140 - 240 °C , Autoclave Guo, Chongshen; Yin, Shu; Yan, Mei; Sato, Tsugio; Journal of Materials Chemistry; vol. 21; nb. 13; (2011); p. 5099 - 5105 View in Reaxys With Amberlyst-15 in n-heptane, T= 159.84 °C , p= 11251.1Torr , Autoclave, Inert atmosphere, Activation energy, Kinetics, Concentration, Reagent/catalyst, Solvent, Temperature, Time Vanoye, Laurent; Zanota, Marie-Line; Desgranges, Audrey; Favre-Reguillon, Alain; De Bellefon, Claude; Applied Catalysis A: General; vol. 394; nb. 1-2; (2011); p. 276 - 280 View in Reaxys With nickel ion-loaded mesoporous silica MCM-41, T= 249.84 °C , p= 760.051Torr , Inert atmosphere, chemoselective reaction Iwamoto, Masakazu; Kasai, Kouji; Haishi, Teruki; ChemSusChem; vol. 4; nb. 8; (2011); p. 1055 - 1058 View in Reaxys With ion-exchange resin Amberlyst 70 in 1,4-dioxane, Time= 150h, T= 136.84 °C , p= 18751.9Torr , Equilibrium constant, Thermodynamic data, Temperature, Time Guilera, Jordi; Ramirez, Eliana; Iborra, Montserrat; Tejero, Javier; Cunill, Fidel; Journal of Chemical and Engineering Data; vol. 58; nb. 7; (2013); p. 2076 - 2082 View in Reaxys The experimental setup consisted in a 200 cm3stainless-steel jacketed batch reactor equipped with a six-blade magneticstirrer (Autoclave Engineers, Pennsylvania, US). The reaction tem-perature range was 323–383 K, controlled within ±0.1 K by a1,2-propanediol–water thermostatic mixture. The system pressurewas kept at 2.0 MPa to ensure the liquid phase over the reaction sys-tem. A detailed description of the experimental setup is describedelsewhere [23].A set of 28 experiments (Table 3) was performed at four differenttemperatures (323, 343, 363 and 383 K) with 3 different initial alco-hol/olefin molar ratio (RA/O= 0.5, 1.0 or 2.0) in order to explore theeffect of different conditions on the side reactions that take placeduring the ETBE synthesis reaction in industrial conditions. With Amberlyst 35 ion exchange resin, Time= 5h, T= 49.84 - 109.84 °C , p= 15001.5Torr , Autoclave Badia; Fite; Bringue; Ramirez; Cunill; Applied Catalysis A: General; vol. 468; (2013); p. 384 - 394 View in Reaxys 2.6. Catalytic experiments General procedure: Catalytic experiments have been performed at atmospheric pressure in a tubular flow reactor using 0.5 g catalyst (60–70 mesh sieved) and feeding 7.9percent v/v ethanol in nitrogen with total flow rate of 80 cc/ min. The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent). The temperature in the experiment was varied stepwise from 423 K to 723 K. , T= 199.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor, Catalytic behavior Phung, Thanh Khoa; Lagazzo, Alberto; Rivero Crespo, Miguel Angel; Sanchez Escribano, Vicente; Busca, Guido; Journal of Catalysis; vol. 311; (2014); p. 102 - 113 View in Reaxys With MFI zeolite nanosheet, T= 110.84 - 151.84 °C , p= 760.051Torr

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Emdadi, Laleh; Wu, Yiqing; Zhu, Guanghui; Chang, Chun-Chih; Fan, Wei; Pham, Trong; Lobo, Raul F.; Liu, Dongxia; Chemistry of Materials; vol. 26; nb. 3; (2014); p. 1345 - 1355 View in Reaxys Table 3 summarizes the catalytic performance of prepared resins and Amberlyst 15 and 46 in the reaction of EOE formation from OcOH and EtOH. Conversion data show that EtOH reacts always faster (XEtOH = 6.1–46.9percent) than OcOH (XOcOH = 2.5–5.0percent). The difference between XEtOH and XOcOH increased clearly with functionalization degree of the resin and, as it is seen, it was particularly noticeable in the more sulfonated catalysts. Fig. 8 displays the OcOH and EtOH conversions as relative values, compared to the most active catalyst, Amberlyst 15. Different trends were observed depending on the reactant. Relative conversions of EtOH increased proportionally as the number of acid centers of the catalysts increased. Thus, it can be assumed that all the acid sites were accessible to EtOH molecules. Much more noticeable was the dependence of the sterically more demanding OcOH conversion on the acid capacity. The OcOH conversion pattern suggests that acidic groups introduced in the polymer during the later stages of the sulfonation process were attached to the least accessible zone of polymer skeleton, where OcOH accessibility was very poor. As for the selectivity, Table 3 reveals that for each alcohol the production of the lower molecular weight ether, the least sterically demanding (SDEE EtOH > SEOE EtOH and SEOE OcOH > SDNOE OcOH was the preferred reaction. Such behavior was more noticeable in the high sulfonated catalysts, what confirms that the reaction was sterically hindered with in those resins. On the fully sulfonated resin Amberlyst 15, only 11percent of the reacted EtOH was converted to EOE, whereas it rose to 32percent on the least sulfonated resin (306). Similar behavior was observed for OcOH. Fig. 9 shows the number of moles of DEE, EOE and DNOE formed over the acidic resins in the OcOH and EtOH reaction, where catalysts are ordered in increasing order of acid capacity. It is seen that the more sulfonated catalysts maximized DEE production. Still, such pattern was not observed for the ethers that require OcOH as reactant (EOE and DNOE). The product distribution profile suggests that the acid centers added in the least accessible zones of the polymer skeleton (the inner ones) do not take significantly part in EOE and DNOE syntheses. With Amberlyst 15, Time= 6h, T= 150 °C , p= 18751.9Torr Guilera, Jordi; Hankova, Libuse; Jerabek, Karel; Ramirez, Eliana; Tejero, Javier; Reactive and Functional Polymers; vol. 78; nb. 1; (2014); p. 14 - 22 View in Reaxys To obtain a rapid evaluation of the catalytic properties, batch experiments were performed by placing ethanol and the catalyst in hermetically sealed steel tubes; these tubes were then placed in a preheated oven for 24h. We used the two types of SPPS, obtained via each of the sulfonation methods, as well as Amberlyst®-15 as catalysts. After the reaction, the liquid was collected and stored, whereas the catalyst was washed and reused at a different temperature. Four runs were performed at 120°C, 150°C and 180°C. The catalytic conversion of ethanol to DEE was measured with a GC (Fig. 3). Ethylene is a side product of ethanol dehydration, especially at high temperatures. No ethylene was observed in the spectra, but if ethylene was produced, it may have escaped before GC was performed. All of the samples contained a trace amount of methanol. The acetyl sulfate-treated samples also contained traces of acetic anhydride, acetic acid and 1,2-dichloroethane. At 120°C and 150°C, Amberlyst®-15 showed the best performance, producing 12percentV/V and 37percentV/V DEE, respectively. At 180°C, the SO3-treated PPS catalyst showed the best performance, resulting in a product that contained 54percentV/V DEE versus 42percentV/V for the Amberlyst®-15 and 35percentV/V for the acetyl sulfate-treated PPS. (0026) After the reaction at 180°C, clear degradation of the steel tube containing Amberlyst®-15 was observed, and all of the catalysts turned darker in color (Supplementary Fig. 5). The catalysts were inspected using SEM–EDX and FTIR to search for degradation. SEM revealed that most of the samples remained visually unchanged from before catalysis (Fig. 4), except for the SO3-treated SPPS, which became more porous, likely due to a partial loss of the skin layer. EDX showed steel degradation products (Fe,CrandNi) in the Amberlyst®-15 sample but not in any of the PPS samples; no other changes in elemental composition were observed (Table 1). IR spectroscopy revealed no significant chemical changes in the SPPS (Supplementary Fig. 6) or Amberlyst®-15 (Supplementary Fig. 7). Importantly, no aliphatic bands appeared in the SPPS samples, indicating that the polymer chains were intact. EDX and IR indicated that despite an obvious loss of sulfonic acid groups from Amberlyst®-15, which initiated the degradation of the steel tube, Amberlyst®-15 retained more sulfonic acid functionality than the SPPS samples after four rounds of catalysis at temperatures up to 180°C. (0027) To investigate the catalytic performance of SPPS in a more realistic scenario, a continuous catalysis setup was created using a heated, packed bed containing 7.0g of SO3-sulfonated PPS catalyst. Ethanol was then pumped through the catalyst at a rate of 1.0mL/min. The resulting liquid was analyzed for DEE content using GC (Fig. 5). DEE production was exponentially dependent on the temperature up to 180°C, after which the dependency was linear to 220°C (Fig. 5a). At 180°C, the processed liquid contained 4.5percentV/V DEE, and at 220°C, the processed liquid contained 14.5percentV/V DEE. An Arrhenius plot of the logarithmic reaction rate versus the inverse temperature (Fig. 5b) reveals a straight line for the exponential range (120–180°C,y=−13008x+20,r2=0.9964) and a poor fit over the entire temperature range (120–220°C,y=−4294x,r2=0.5921) due to the linear range above 180°C. From the 120–

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180°C slope (−Ea/R), we calculate the activation energy for the reaction as 108kJmol−1K−1 using the formula ln(k)=ln(A)−Ea/R1/T. (0028) Having established that PPS could be converted into a catalytic substrate using sulfuric acid, we sought to develop a porous structure with a large surface area that could be used as an improved catalytic substrate. PPS powder was mixed with NaCl, compressed, melted, compressed again and cooled. The NaCl was then washed off, leaving a porous substrate (Fig. 6a, left picture). This substrate was confirmed to be porous using a CT scan (Fig. 6b and c). The scan showed clear interconnected voids shaped similar to NaCl crystals, and the substrate was determined to be 71percent porous. Porous PPS cylinders were then treated with 100percent H2SO4 at either room temperature or at 0°C. The resulting substrates were dried and photographed (Fig. 6a). The sample sulfonated at room temperature had a charred surface and a white center, whereas the sample treated at 0°C had a white surface and center. The sample sulfonated at 0°C was then placed in a closed container with 5mL of ethanol, and catalytic activity was evaluated in a single sample batch experiment over 19h at 170°C and 12bar. The resulting liquid contained 2.1percentV/V DEE. With Amberlyst-15, Time= 19h, T= 170 °C , p= 9000.9Torr , Sealed tube, Activation energy, Temperature, Reagent/ catalyst Zwettler, Niklas; Engbaek, Jakob S.; Lundsgaard, Rasmus; Paranowska, Irena; Nielsen, Tina E.; Clyens, Stuart; Christiansen, Jens; Andersen, Morten .; Reactive and Functional Polymers; vol. 88; (2015); p. 47 - 54 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. , T= 149.84 °C , p= 760.051Torr , Inert atmosphere, Catalytic behavior, Reagent/catalyst, Temperature Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys 5 : Catalyst Evaluation General procedure: The above catalysts were prepared and evaluated. γ-Aluminum oxide, zirconium oxide without any metal coating were evaluated under the same testing conditions to serve as control. A fixed bed gas flow catalytic reactor was used as a reactor. 3 ml of the catalysts was filled in a stainless steel tube reactor with a diameter of 0.95 cm. As a pretreatment, hydrogen reduction was conducted for 1 hour under a carrier gas atmosphere (10percent H2/N2 base; flow rate 125 ml/min) at 400° C. After the pretreatment, the testing was conducted at a temperature between 250° C. and 325° C. and pressure between 1 kPa and 5,100 kPa, nitrogen flow rate was at 125 sccm and ethanol flow rate was at 0.2 ml/min. The reaction duration ranges from 5 hours to 80 hours. With γ-alumina, hydrogen, T= 270 °C , p= 25502.6Torr , Flow reactor, Inert atmosphere, Reagent/catalyst Patent; Celanese International Corporation; Zhang, Cheng; Balliet, Kenneth; Johnston, Victor J.; US9024090; (2015); (B2) English View in Reaxys Catalytic experiments Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70mesh sieved, to have a ratio between the particle diameter and theinternal reactor diameter near 25) and feeding 7.9percent (v/v) ethanol innitrogen with 1.43 h−1WHSV (total flow rate of 80 cc/min). The car-rier gas (nitrogen) was passed through a bubbler containing ethanol(96percent) maintained at constant temperature (298 K) in order to obtainthe desired partial pressures. The temperature in the experimentwas varied stepwise from 373 to 623 K. With H-BEA zeolite, T= 199.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor, Catalytic behavior, Reagent/ catalyst, Temperature Phung, Thanh Khoa; Proietti Hernndez, Loriana; Lagazzo, Alberto; Busca, Guido; Applied Catalysis A: General; vol. 493; (2015); p. 77 - 89 View in Reaxys 1.A; 1.B :Said ethanol feedstock is introduced, at a flow rate of 45,664 kg/h, into an exchanger E1 at a pressure equal to 1.15 MPa and is heated, remaining in the liquid phase, to a temperature of 120° C. against the effluent from

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the last adiabatic reactor of step e). Step b) (0117) The heated ethanol feedstock is pretreated on TA801 resin to remove the traces of nitrogen-containing compounds. During this pretreatment, a portion of the ethanol is converted to DEE. The characteristics of the raw ethanol feedstock and of the pretreated feedstock are given in Table 1. With TA801 resin in water, T= 120 °C , p= 8625.86Torr , Gas phase, Flow reactor Patent; TOTAL RESEARCH and TECHNOLOGY FELUY; IFP ENERGIES NOUVELLES; COUPARD, Vincent; TOUCHAIS, Natacha; PLENNEVAUX, Thomas; KOBEL, Emilie; FLEURIER, Stephanie; VERMEIREN, Walter; MINOUX, Delphine; DE SMEDT, Philip; ADAM, Cindy; NESTERENKO, Nikolai; US2015/299068; (2015); (A1) English View in Reaxys OH

Rx-ID: 39883714 View in Reaxys 2/630 Yield

Conditions & References Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. With sulphate containing titania, T= 349.84 °C , p= 760.051Torr , Inert atmosphere Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys With Li(1+)*2Zr(4+)*3O4P(3-) Il'in; Ermilova; Orekhova; Yaroslavtsev; Inorganic Materials; vol. 51; nb. 7; (2015); p. 711 - 717; Neoorg. Mater.; vol. 51; nb. 7; (2015); p. 778 - 784 View in Reaxys 1.A; 1.B; 1.C; 1.D; 1.E :Said ethanol feedstock is introduced, at a flow rate of 45,664 kg/h, into an exchanger E1 at a pressure equal to 1.15 MPa and is heated, remaining in the liquid phase, to a temperature of 120° C. against the effluent from the last adiabatic reactor of step e). Step b) (0117) The heated ethanol feedstock is pretreated on TA801 resin to remove the traces of nitrogen-containing compounds. During this pretreatment, a portion of the ethanol is converted to DEE. The characteristics of the raw ethanol feedstock and of the pretreated feedstock are given in Table 1. The vaporization feedstock, constituted by the pretreated ethanol feedstock mixed with 141,252 kg/h of treated water and of unconverted ethanol recycled according to step h), is depressurized and introduced into an exchanger E2 at a pressure equal to 0.27 MPa. The bubble point of this feedstock at this pressure is 127° C. taking into account the presence of DEE. The vaporization feedstock enters exchanger E2 at 113° C. and is therefore already vaporized at 8.6percent by weight. The pressure at the inlet of exchanger E2 was adjusted in such a way that the temperature approach with the flow from the last adiabatic reactor of step e) is at a minimum of 15° C. (0119) In step c), most of the latent heat of the aqueous phase of the effluent from the last adiabatic reactor of step e) is recovered for vaporizing the vaporization feedstock, without external heat supply. Thus, 93.6 MW is exchanged between said vaporization feedstock and said effluent. Step d) (0120) The vaporized feedstock is then compressed in a radial compressor with an integrated multiplier so that the pressure of said vaporized feedstock is equal to 0.695 MPa at the end of the compression. (0121) The compressed feedstock is then heated in an exchanger E3 of the singlephase gas type, by means of heat exchange with the effluent from the adiabatic reactor of step e). In said exchanger of the single-phase gas type, said compressed feedstock is superheated to a temperature of 405° C. and the effluent leaving, in the gaseous state, the last adiabatic reactor of step e) is “desuperheated” without being condensed, and has a temperature of 253° C. Step e) (0122) Said compressed feedstock, heated in said exchanger of the singlephase gas type, is then introduced into a furnace so as to bring it to an inlet temperature in the first adiabatic reactor of step e) compatible with the temperature of the highly endothermic reaction of dehydration and of conversion of DEE to ethylene, i.e. to a temperature of 440° C. The outlet temperature of the last adiabatic reactor of step e) is 420° C. (0123) The trapping of the nitrogen-containing compounds in the pretreatment step b) makes it possible to reduce the inlet temperature of the first adiabatic reactor of step e) significantly. (0124) Said compressed and heated feedstock is introduced into the first adiabatic reactor at an inlet pressure of 0.595 MPa. The pressure of the effluent at the outlet of the last adiabatic reactor of step e) is 0.500 MPa. The dehydration step e) is carried out at a weight

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hourly space velocity of 7 h−1. (0125) The adiabatic reactor contains a fixed bed of dehydration catalyst, said catalyst comprising 80percent by weight of zeolite ZSM-5 treated with H3PO4 so that the content of phosphorus P is 3percent by weight. (0126) The conversion of the ethanol feedstock in step e) is 95percent. Stage 1: With TA801 resin in water, T= 120 °C , p= 8625.86Torr , Gas phase, Flow reactor Stage 2: With zeolite ZSM-5 treated with H3PO4 in water, T= 405 - 440 °C , p= 2025.2 - 4462.95Torr , Gas phase, Flow reactor Patent; TOTAL RESEARCH and TECHNOLOGY FELUY; IFP ENERGIES NOUVELLES; COUPARD, Vincent; TOUCHAIS, Natacha; PLENNEVAUX, Thomas; KOBEL, Emilie; FLEURIER, Stephanie; VERMEIREN, Walter; MINOUX, Delphine; DE SMEDT, Philip; ADAM, Cindy; NESTERENKO, Nikolai; US2015/299068; (2015); (A1) English View in Reaxys O

Rx-ID: 23052169 View in Reaxys 3/630 Yield 92.7 %, 3.6 %, 3.2 %

Conditions & References 1 : Comparative Example 1 The catalyst used was the same as used in Example 1. Using the reactor shown in Fig. 2, ethylene, nitrogen, acetic acid and water were fed in a molar ratio of 80.0:10.3:6.7:3.0 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Nitrogen was fed together with ethylene and water was fed together with acetic acid. When the temperature of the evaporator was set to be the same as in Example 1 (92.4°C), the acetic acidwater mixture did not vaporize and only ethylene was fed to the reactor. As a result, a polymerization reaction of ethylene occurred on the catalyst in the reactor and the catalyst was deactivated. Then, the temperature of the evaporator was elevated to a temperature where the acetic acid-water mixture vaporized, and the temperature was 194.4°C. When the peak temperature of the catalyst layer was 165°C, the reaction results were such that the STY of ethyl acetate was 198 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 92.7percent, 3.6percent and 3.2percent, respectively. Stage 1: With water, T= 92.4 °C Stage 2: With cesium nitrate; tungstophosphoric acid; water; mixture of, dried, tabletted, T= 92.4 - 194.4 °C , p= 6750.68Torr , Gas phase, Product distribution / selectivity Patent; SHOWA, DENKO K.K.; EP1218331; (2004); (B1) English View in Reaxys

91.5 - 93.0 %, 3.4 4.3 %, 3.0 - 3.7 %

1, 2 : Example1; Catalyst The catalyst used in this Example was a tablet-shaped catalyst comprising a cesium salt of tungstophosphoric acid and having a diameter of 5 mm. This catalyst was prepared as follows. In 300 ml-volume flask, 150 g (about 0.0438 mol) of a commercially available tungstophosphoric acid reagent (produced by Wako Junyaku K.K.) was mixed and dissolved in 60 ml of pure water. Separately, 21.5 g (0.110 mol) of cesium nitrate (CsNO3) was dissolved in water and the resulting solution was added dropwise to the aqueous tungstophosphoric acid solution prepared above, using a dropping funnel while stirring. The moment the solution was added dropwise, white fine crystals of phosphowolframate (tungstophosphoric acid cesium salt) were precipitated. The flask was dipped in a water bath to vaporize the water content and the residual lump was transferred to a Petri dish, placed in a dryer and dried in air at 150°C for 6 hours. The dried product was pulverized and formed into tablets having a diameter of 5 mm using a tablet machine. Using the reactor shown in Fig. 1, ethylene, nitrogen, acetic acid and water were fed in a molar ratio of 80.0:10.3:6.7:3.0 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Nitrogen was fed together with ethylene and water was fed together with acetic acid. In this case, the temperature at which the acetic acid-water mixture vaporized was 92.4°C. When the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the space time yield STY of ethyl acetate was 200 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 93.0percent, 3.4percent and 3.0percent, respectively. Example 2 The catalyst used was the same as that used in Example 1. Using the reactor shown in Fig. 1, ethylene, acetic acid and water were fed in a molar ratio of 87.0:5.0:8.0 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Water was fed together with acetic acid. In this case, the temperature at which the acetic acid-water mixture vaporized was 102.3°C. When the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the STY of ethyl acetate was 176 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 91.5percent, 4.3percent and 3.7percent, respectively.

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With water, cesium nitrate; tungstophosphoric acid; water; mixture of, dried, tabletted, T= 92.4 - 165 °C , p= 6750.68Torr , Gas phase, Product distribution / selectivity Patent; SHOWA, DENKO K.K.; EP1218331; (2004); (B1) English View in Reaxys 90.1 - 92.1 %, 5.0 6.6 %, 2.2 - 4.2 %

5, 6, 8 : Example 5 The catalyst used was a catalyst obtained by allowing a lithium salt of tungstophosphoric acid to be supported on a silica support (produced by Sudchemie GmbH) having a diameter of 5 mm. This catalyst was prepared as follows. The support was dried in a hot air dryer at 110°C for 4 hours to have a residual water content of 7percent or less. In a 500 ml-volume flask, 298 g (about 0.104 mol) of a commercially available tungstophosphoric acid reagent (produced by Wako Junyaku K.K.) was mixed and dissolved under heating in 120 ml of pure water. Separately, 0.076 g (0.0011 mol) of lithium nitrate (LiNO3) was dissolved in pure water and the resulting solution was added dropwise to the aqueous tungstophosphoric acid solution prepared above, using a dropping funnel while stirring. The stirring was continued at room temperature for 30 minutes to obtain a uniform solution and, to the resulting solution, pure water was added until the volume reached 95percent of the saturated liquid absorption amount of the supporter, thereby forming an impregnating solution. To this impregnating solution, 1 L of the support was added, and then the solution was thoroughly stirred to completely impregnate the support and thereby allow the catalyst to be uniformly supported. The resulting impregnated product was air dried for 1 hour and then dried in a hot air dryer at 150°C for 5 hours to obtain a supported catalyst. The thus-obtained catalyst was filled in the reactor shown in Fig. 1 and, thereto, ethylene, nitrogen, acetic acid and water were fed in a molar ratio of 78.5:9.0:8.0:4.5 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Nitrogen was fed together with ethylene and water was fed together with acetic acid. In this case, the temperature at which the acetic acid-water mixture vaporized was 102.2°C. When the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the space time yield STY of ethyl acetate was 215 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 90.8percent, 5.0percent and 4.2percent, respectively.Example 6 A catalyst was prepared in the same manner as in the catalyst preparation procedure in Example 5, except that 0.007 g (0.0001 mol) of lithium nitrate was used. The thus-obtained catalyst was filled in the reactor shown in Fig. 1 and, thereto, ethylene, nitrogen, acetic acid and water were fed in a molar ratio of 78.5:9.0:8.0:4.5 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Nitrogen was fed together with ethylene and water was fed together with acetic acid. In this case, the temperature at which the acetic acid-water mixture vaporized was 102.2°C. When the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the space time yield STY of ethyl acetate was 174 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 92.1percent, 5.7percent and 2.2percent, respectively. Example 8 A catalyst was prepared in the same manner as in the catalyst preparation procedure in Example 5, except that 541 g (0.194 mol) of tungstophosphoric acid was used instead of 298 g of tungstophosphoric acid and 1.323 g (0.0012 mol) of lithium nitrate was used instead of 0.076 g. The thus-obtained catalyst was filled in the reactor shown in Fig. 1 and thereto, ethylene, nitrogen, acetic acid and water were fed in a molar ratio of 78.5:9.0:8.0:4.5 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Nitrogen was fed together with ethylene and water was fed together with acetic acid. In this case, the temperature at which the acetic acid-water mixture vaporized was 102.2°C. When the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the space time yield STY of ethyl acetate was 196 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 90.1percent, 6.6percent and 3.3percent, respectively. With water, lithium nitrate; silica; tungstophosphoric acid; water; mixture of, heated at 150 C, T= 102.2 - 165 °C , p= 6750.68Torr , Gas phase, Product distribution / selectivity Patent; SHOWA, DENKO K.K.; EP1218331; (2004); (B1) English View in Reaxys

87.7 %, 7.6 %, 4.7 %

7 : Example 7 A catalyst was prepared in the same manner as in the catalyst preparation procedure in Example 5, except that 345 g (0.120 mol) of tungstosilicic acid and 0.083 g (0.120 mol) of lithium nitrate were used. The thus-obtained catalyst was filled in the reactor shown in Fig. 1 and, thereto, ethylene, nitrogen, acetic acid and water were fed in a molar ratio of 78.5:9.0:8.0:4.5 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.9 MPa. Nitrogen was fed together with ethylene and water was fed together with acetic acid. In this case, the temperature at which the acetic acid-water mixture vaporized was 102.2°C. when the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the space time yield STY of ethyl acetate was 254 g/l-cat.bul.h and the selectivities of ethyl acetate, ethanol and diethyl ether were 87.7percent, 7.6percent and 4.7percent, respectively With water, lithium nitrate; silica; tungstosilicic acid; water; mixture of, heated at 150 C, T= 102.2 - 165 °C , p= 6750.68Torr , Gas phase, Conversion of starting material

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Patent; SHOWA, DENKO K.K.; EP1218331; (2004); (B1) English View in Reaxys

Rx-ID: 38240930 View in Reaxys 4/630 Yield

Conditions & References 2.5.1. Resin screening General procedure: 2.5.1. Resin screening Wet resins (as provided by the supplier) were dried at room temperature for 24 h prior to mechanical sieving. Resin samples with bead size between 0.40 and 0.63 mm were dried at 110C, firstly at 1 bar for 2 h and then at 10 mbar for 15 h. 1-butanol was charged in the reactor and heated to 150C. The reaction mixture was pressurized to 40 bar by means of N2 in order to assure the liquid phase reaction medium. The stirring speed was set at 500 rpm. After reaching the working temperature, 1 g of dry catalyst was was injected by means of pneumatic transport. That moment was con-sidered the starting point of reaction. To follow the variation of concentration of reactants and products with time, liquid samples were taken out hourly and analyzed online as mentioned above. Total length of the experiments was 7 h. In all the experiments mass balance was accomplished within ± 8percent. With Amberlyst 36 in acetone, Time= 7h, T= 150 °C , p= 30.003Torr Perez; Bringue; Iborra; Tejero; Cunill; Applied Catalysis A: General; vol. 482; (2014); p. 38 - 48 View in Reaxys

F Br F

F F

HO F

F F

Rx-ID: 28985525 View in Reaxys 5/630 Yield

Conditions & References

48.6 %, 47.0 %

A 1-liter flask was evacuated and the inside thereof was replaced with nitrogen gas and then a still was charged with 115 g (1.76 mol) of zinc powder and 400 ml of dehydrated DMF. Then the dropping funnel was charged with 208 g (0.8 mol) of CF3CFBr2 and 100 ml of dehydrated DMF, followed by heating and stirring in nitrogen gas atmosphere. After that, while maintaining at 80 to 90C, titration was continued over two hours, followed by heating and stirring at 90 to 95C for 4.5 hours. Dimroth condenser was changed to dry ice/acetone condenser and while cooling the still, CF3COCF3 gas was introduced at room temperature. The introduction of CF3COCF3 was terminated at the time when it was determined that the refluxing did not stop and the reaction did not advance. An amount of the introduced gas was 92 g (0.55 mol). Then, after releasing the un-reacted CF3COCF3 by heating and evacuating, diethyl ether was added, followed by washing an organic layer with 1N hydrochloric acid and drying with CaCl2. As a result of refining by rectification using a rectification tower filled with a filler, 56.6 g of a mixture solution comprising 48.6 percent of 1,1-bistrifluoromethyl-2,3,3-trifluoro-2-propene-1-ol (CF2=CFC(CF3)2OH) and 47.0 percent of diethyl ether in an area ratio by GC.19F-NMR (solvent: CDCl3): -77.0 (6F, q), -91.6 (1F, dd), -106.8 (1F, m), - 184.1 (1F, m) MS: 248 (M+), 209, 181, 179, 159, 109, 69 (CF3), 31 (CF) Stage 1: With zinc in DMF (N,N-dimethyl-formamide), Time= 6.5h, T= 80 - 95 °C Stage 2:, T= 20 °C Patent; Daikin Industries, Ltd.; EP1415974; (2004); (A1) English View in Reaxys

Rx-ID: 39948577 View in Reaxys 6/630 Yield 40 %

Conditions & References 5 : Catalyst Evaluation General procedure: The above catalysts were prepared and evaluated. γ-Aluminum oxide, zirconium oxide without any metal coating were evaluated under the same testing conditions to serve as control. A fixed bed gas flow catalytic reactor was used as a reactor. 3 ml of the catalysts was filled in a stainless steel tube reactor with a diameter of 0.95 cm. As a pretreatment, hydrogen reduction was conducted for 1 hour under a carrier gas atmosphere (10percent H2/N2 base; flow rate 125 ml/min) at 400° C. After the pretreatment, the testing was conducted at a temperature

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between 250° C. and 325° C. and pressure between 1 kPa and 5,100 kPa, nitrogen flow rate was at 125 sccm and ethanol flow rate was at 0.2 ml/min. The reaction duration ranges from 5 hours to 80 hours. With hydrogen, T= 400 °C , p= 25502.6Torr , Flow reactor, Inert atmosphere Patent; Celanese International Corporation; Zhang, Cheng; Balliet, Kenneth; Johnston, Victor J.; US9024090; (2015); (B2) English View in Reaxys OH

Rx-ID: 193869 View in Reaxys 7/630 Yield 0.1 %, 98.9 %

Conditions & References 2. Experimental General procedure: Catalytic experiments were performed at atmospheric pressure in a tubular flow reactor feeding 7.9percent v/v ethanol in nitrogen at 298 K (total flow rate of 80 cm3/min) as described in our previous studies With Catalox® SCFa-140 gamma-alumina, T= 449.84 °C , Inert atmosphere, Catalytic behavior, Reagent/catalyst, Temperature, Overall yield = 100 percent Phung, Thanh Khoa; Busca, Guido; Catalysis Communications; vol. 68; (2015); p. 110 - 115 View in Reaxys

50.0 %, 10.0 %

21 :The same method was followed as described for examples 1-14, only the reaction was performed in a 300 ml capacity stainless steel autoclave at 110° C. and 4 ml of the required alcohol as indicated was used instead of hexan-1-ol. With C2I2O2Rh(1-)*C8H20N(1+), tetraethylammonium iodide, hydrogen iodide in water, T= 110 °C , Inert atmosphere, Autoclave, Product distribution / selectivity Patent; Wass, Duncan Frank; Shishkov, Igor Viacheslavovich; US2010/267996; (2010); (A1) English View in Reaxys

12 %

9 :Absolute ethanol (46.1 g) was dropped onto the ionic liquid [MIPS]/[HOTf] (1:1.5) (10 mmol / 15 mmol) at 240 to 260 deg. C. The product was collected in a Schlenk flask attached to the outlet of the condenser and cooled with liquid nitrogen. After 4 hours, 3.24 EPO <DP n="17"/>g ethene was collected in the Schlenk flask (along with 2.17 g diethyl ether and ethanol), corresponding to a yield of 12percent of ethene.Again, the water by-product inhibited this reaction. Higher temperatures and a water separation step would improve the yield. With [PMIM(SO3H)[OTf]], CF3O3S(1-)*CHF3O3S*C7H13N2O3S(1+), Time= 4h, T= 240 - 260 °C , Product distribution / selectivity Patent; BP p.l.c.; WO2007/12825; (2007); (A1) English View in Reaxys katalytische Dehydratisierung Pines; Manassen; ; vol. 16; (1966); p. 49,71 View in Reaxys Winfield in P.H.Emmett; View in Reaxys Leiten ueber mit H2SO4 getraenkten Bimsstein Senderens; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 192; (1931); p. 1335 View in Reaxys With zirconium(IV) bis(monohydrogenphosphate), T= 540 - 610 °C , p= 760Torr , Zr(HPO3)2 (calcined, uncalcined), α-Zr(HPO4)2; rates of dehydration, apparent activation energies, mechanism, Rate constant, Product distribution, Thermodynamic data Wan, Ben-Zu; Cheng, Soofin; Anthony, Rayford G.; Clearfield, Abraham; Journal of the Chemical Society, Faraday Transactions; vol. 87; nb. 9; (1991); p. 1419 - 1424 View in Reaxys

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With H3[PW12O40], T= 129.9 °C , var. partial pressure of ethanol, Product distribution, Mechanism Lee, Kwan Young; Arai, Takeo; Nakata, Shin-Ichi; Asaoka, Sachio; Okuhara, Toshio; Misono, Makoto; Journal of the American Chemical Society; vol. 114; nb. 8; (1992); p. 2836 - 2842 View in Reaxys With clinoptilolite concentrate in gaseous matrix, T= 238.9 °C , dehydration reactions on different reagents at different temperatures and times, Product distribution, Kinetics, Mechanism Skundric, B.; Spanic, M.; Cegar, N.; Zeitschrift fuer Physikalische Chemie (Muenchen, Germany); vol. 132; (1982); p. 93 - 104 View in Reaxys With H3[PW12O40], T= 130 °C , variation of pressure, Product distribution Misono, Makoto; Okuhara, Toshio; Ichiki, Tatsumi; Arai, Takeo; Kanda, Yuji; Journal of the American Chemical Society; vol. 109; nb. 18; (1987); p. 5535 - 5536 View in Reaxys 4 :Choline dihydrogen phosphate was used in the dehydration of ethanol at temperatures of up to 375°C. Approximately 10percent of the ethanol was converted to diethyl ether and an unquantifed amount of ethylene. With CDHP, T= 375 °C , Product distribution / selectivity Patent; BP p.l.c.; WO2007/12825; (2007); (A1) English View in Reaxys The feed, consisting of 500 kte/y (57 te/h) of 80percent ethanol, 20percent water is fed into a reactive distillation column (column 1). The column consists of 40 theoretical trays (plates). The feed enters the said column on tray 30, and the reactive section was set from trays 10 to 20 (numbered from the top).The reaction is assumed to be fast, that is, equilibrium is achieved on each tray. The top of the reactive distillation column is also equipped with a partial condenser (using cooling water at 40°C). The reboiler is positioned at the base of the said column and is operated with steam. The overhead vapour from the partial condenser of the reactive distillation column flows to base of column 2, where column 2 consists of 20 theoretical trays. Vapour flow from the overhead of column 2 is partially condensed by refrigeration, at -400C. The liquid from the base of column 2 is returned to the reactive distillation column, as a reflux return.The vapour take-off from the top of the reactive distillation column after partial condensation was found to consist of ethylene with approximately 5.67percent w/w diethyl ether (DEE), 0.14percent w/w water and less than lppm ethanol.The vapour take-off from the top of column 2 was found to contain ethylene with approximately lppm DEE, negligible water and ethanol.The liquid product from the base of the reactive distillation column, was found to contain water, with a negligible level of impurity, suitable for discharge direct to effluent.For completeness, the model also gave the following heat exchange duties: Reactive distillation condenser: 29.5 MW EPO <DP n="17"/ >Column 2 condenser: 3.0 MW Reactive distillation reboiler: 37.3 MWThis illustrates the advantage of employing partial condensation on the reactive distillation together with an ethylene polishing column 2. The expensive refrigerated condenser duty required for olefin polishing has been reduced considerably by separating it from the reactive distillation column. Mass BalanceFeed Vapour Liquid Overhead BaseCol l->2 Col 2->l Product Product(column 2) (column 1)Kmol/h Kmol/h Kmol/h Kmol/h Kmol/hDEE 0.0 62.5 62.5 0.0 0.0Ethanol 991.2 0.0 0.0 0.0 0.0Ethylene 0.0 1037.4 46.2 991.2 0.0Water 633.7 1.5 1.5 0.0 1624.9 in water, Industry scale Patent; BP CHEMICALS LIMITED; WO2007/3899; (2007); (A1) English View in Reaxys With 12-tungstophosphoric acid in W/O microemulsion, T= 29.84 - 299.84 °C , Inert atmosphere Okada, Tomohiko; Mishima, Shozi; Yoshihara, Shingo; Chemistry Letters; vol. 38; nb. 1; (2009); p. 32 - 33 View in Reaxys 65.7 %Chromat., 24.8 %Chromat.

10.8 :Example 10The solid component (unfired) C12-MCM-41 obtained in Reference Example 1 was finely ground down in a mortar, thinly spread on a magnetic dish, introduced into an electric furnace, heated up to 773K at a rate of 5 K/min., and was fired at this temperature for 6 hours.Next, the effect of the C12-MCM-41 without supporting nickel was examined in producing olefin from the ethyl alcohol. The experimental conditions were the same as those of Example 6 but using the C12-MCM-41 as catalyst. The results were as shown in Table 2. Over 623K, ethylene was formed nearly quantitatively. From a comparison with Table 1, it was obvious that the addition of nickel ions helped form propylene and butene.

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With C12-MCM-41, T= 573 °C , p= 750.075Torr , Gas phase, Inert atmosphere Patent; Iwamoto, Masakazu; Yamamoto, Takashi; Haishi, Teruki; US2010/168491; (2010); (A1) English View in Reaxys With aluminum oxide, T= 300 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys With Rh2Cl2(CO)4, tris(2,4,6-trimethylphenyl)phosphine, tetrabutylammomium bromide, hydrogen iodide in water, Time= 48h, T= 110 °C Dowson, George R. M.; Shishkov, Igor V.; Wass, Duncan F.; Organometallics; vol. 29; nb. 18; (2010); p. 4001 4003 View in Reaxys 2 :[0026] An ethyl alcohol/water feed (92 weight percent ethyl alcohol) is heated in a furnace and fed to an initial adiabatic reactor containing alumina catalyst at 3000C and at 0.3 MPa pressure absolute. This generates a first reaction product containing unreacted ethyl alcohol, water (both generated and diluent), diethyl ether, and some ethene. The first reaction product exits the first reactor at a temperature close to the temperature at which it entered the first reactor. The mass fraction of water is increased from 8 weight percent, in the initial feed, to greater than 20 weight percent in the first reaction product. This first reaction product is then fed to three subsequent adiabatic reactors operating in series, each at reactor inlet temperatures of 45O0C and at pressures ranging from 0.1 and 0.2 MPa absolute. Total LHSV of the reactors is approximately 0.5 (on a water-free basis), resulting in a greater than 98 percent conversion of ethyl alcohol to ethene. The total vapor volume is reduced by a factor of six and the amount of total water requiring separation and post treatment is also reduced, when compared with amounts shown in Example 1 (Comparative). With aluminum oxide in water, T= 300 °C , p= 2250.23Torr , Product distribution / selectivity Patent; DOW GLOBAL TECHNOLOGIES INC.; STEWART, Mark; CLARK, Howard; COFFEY, Duncan; LUO, Lin; SCHWEIZER, Albert E. Jr.; WO2011/2699; (2011); (A2) English View in Reaxys 2 :Example 2Dehydration of ethanol over H3PO4 (20 wt percent) modified H-ZSM-5 catalyst was conducted under similar reaction conditions to those described in Comparative Example 1 with increasing reaction temperature from 250 to 450° C. H3PO4 modified H-ZSM-5 catalysts were prepared according to the protocol described above under heading A. The results of ethanol dehydration activity on the H3PO4/H-ZSM-5 catalyst are presented in Table 3. An increase of the conversion of ethanol from 50percent to 99percent was observed with the increase in reaction temperature. An increase of the ethylene selectivity with an increase in reaction temperature was also observed. Ethanol dehydration activity on H3PO4 (20wt percent) on H-ZSM-5 catalyst at 400° C. and 1 atm of pressure is shown in FIG. 3. As can be seen from FIG. 3, no deactivation was observed after running for 110 hours. With 20 wtpercent H3PO4-modified H-ZSM-5 catalyst, T= 350 °C , p= 760.051Torr , Product distribution / selectivity Patent; Ramesh, Kanaparthi; Borgna, Armando; US2011/98519; (2011); (A1) English View in Reaxys With submicron MFI zeolite in water, Heating Wang, Fei; Luo, Man; Xiao, Wende; Cheng, Xiaowei; Long, Yingcai; Applied Catalysis A: General; vol. 393; nb. 1-2; (2011); p. 161 - 170 View in Reaxys With reduced Copper salt of diphosphooctadecatungstic acid (Wells-Dawson type), Time= 2.5h, T= 210 °C , Inert atmosphere Filek, Urszula; Bielanska, Elbieta; Socha, Robert P.; Bielanski, Adam; Catalysis Today; vol. 169; nb. 1; (2011); p. 150 - 155 View in Reaxys With aluminum oxide, T= 150 - 300 °C , Inert atmosphere

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Martins, Leandro; Cardoso, Dilson; Hammer, Peter; Garetto, Teresita; Pulcinelli, Sandra H.; Santilli, Celso V.; Applied Catalysis A: General; vol. 398; nb. 1-2; (2011); p. 59 - 65 View in Reaxys With nickel ion-loaded mesoporous silica MCM-41, T= 299.84 °C , p= 760.051Torr , Inert atmosphere, chemoselective reaction Iwamoto, Masakazu; Kasai, Kouji; Haishi, Teruki; ChemSusChem; vol. 4; nb. 8; (2011); p. 1055 - 1058 View in Reaxys With pyridine, Catalox® SCFa-140 gamma-alumina, T= 214.84 °C , p= 760.051Torr , Inert atmosphere, Kinetics, Mechanism, Pressure DeWilde, Joseph F.; Chiang, Hsu; Hickman, Daniel A.; Ho, Christopher R.; Bhan, Aditya; ACS Catalysis; vol. 3; nb. 4; (2013); p. 798 - 807 View in Reaxys Dehydration of ethanol 0.5 g of the catalyst was placed in a fixed bed flow reactor (10 mm i.d.) and supported by quartz wool from both ends. It was activated at 250 °C in the presence of N2 (30 ml min–1) for 2 h. Then, bioethanol (80percent) was fed using a syringe pump into N2 stream, at a weight hourly space velocity (WHSV) of 1 h–1 and atmospheric pressure. Each reaction was performed for a period of 5 h. The temperature was varied in a range of 200–350 °C. The products were condensed and analyzed offline using a gas chromatograph (Hewlett Packard-6890) with a Porapak T column and a TCD detector. With 30percent cerium phosphotungstate supported on MCM-41, Time= 5h, T= 300 °C , p= 760.051Torr , Flow reactor, Inert atmosphere, Catalytic behavior, Temperature, Reagent/catalyst Trakarnpruk, Wimonrat; Mendeleev Communications; vol. 23; nb. 3; (2013); p. 168 - 170 View in Reaxys 2.3. Catalytic tests The experiments of ethanol dehydration were carried out usinga quartz flow-through microreactor at the reaction temperatureranging from 373 to 473 K. The nitrogen gas was passed over theliquid ethanol at 293 K, thus, the concentration of ethanol vapourin the flowing helium was 15 g/m3. Typically, 0.5 cm3of catalystsample (0.25–0.50 mm fraction) was placed in the reactor and therate of helium was 5 L/h, thus, the space velocity GHSV was equalto 10,000 h−1. Prior to the reaction, the samples were standardizedin the helium at 373 K for 2 h. The relative humidity (RH) of usedhelium was 2percent. The conditions of catalytic tests used in the presentstudies were the same as those in our previous research concerningthe dehydration of ethanol over K, Cs and Ag salts of HPW [5,8,36]. Itwas previously experimentally determined that in such conditionsthe influence of diffusion processes could be neglected.The catalyst sample was heated in a given temperature for0.5 h to attain the steady state. Then, the products were analyzedusing SRI 8610B gas chromatograph equipped with HayeSep Dpacked column (3 m, 100–120 mesh) and both TCD and FID detec-tors arranged one by one. Thus, with one sample injection, thefollowing products such as ethylene, diethyl ether, acetic aldehydeand carbon oxides were detected and recognized. The content ofproducts was calculated from the calibration curves prepared foreach analyzed reagent. With 2K(1+)*H(1+)*PW12O40 (3-) = K2HPW12O40, T= 99.84 - 199.84 °C , Inert atmosphere, Catalytic behavior, Temperature Matachowski; Drelinkiewicz; Lalik; Ruggiero-Mikolajczyk; Mucha; Krysciak-Czerwenka; Applied Catalysis A: General; vol. 469; (2014); p. 290 - 299 View in Reaxys 2.6. Catalytic experiments General procedure: Catalytic experiments have been performed at atmospheric pressure in a tubular flow reactor using 0.5 g catalyst (60–70 mesh sieved) and feeding 7.9percent v/v ethanol in nitrogen with total flow rate of 80 cc/ min. The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent). The temperature in the experiment was varied stepwise from 423 K to 723 K. , T= 249.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor, Catalytic behavior Phung, Thanh Khoa; Lagazzo, Alberto; Rivero Crespo, Miguel Angel; Sanchez Escribano, Vicente; Busca, Guido; Journal of Catalysis; vol. 311; (2014); p. 102 - 113 View in Reaxys

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2.6. Catalytic experiments General procedure: Catalytic experiments have been performed at atmospheric pressure in a tubular flow reactor using 0.5 g catalyst (60–70 mesh sieved) and feeding 7.9percent v/v ethanol in nitrogen with total flow rate of 80 cc/ min. The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent). The temperature in the experiment was varied stepwise from 423 K to 723 K. , T= 299.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor, Catalytic behavior Phung, Thanh Khoa; Lagazzo, Alberto; Rivero Crespo, Miguel Angel; Sanchez Escribano, Vicente; Busca, Guido; Journal of Catalysis; vol. 311; (2014); p. 102 - 113 View in Reaxys With Cs2HPW12O40, Time= 2.5h, T= 19.84 - 199.84 °C , Inert atmosphere Matachowski; Drelinkiewicz; Mucha; Krysciak-Czerwenka; Rachwalik; Applied Catalysis A: General; vol. 469; (2014); p. 239 - 249 View in Reaxys General procedure: The catalysts used in this study are P25 TiO2 (Evonik) and withPd at a loading of 5 wtpercent Pd/TiO2. PdCl2 (0.1667 g, Sigma–Aldrich)was dissolved in 1.5 ml deionised water, acidified with HCl to pH1, and then added drop-wise onto 2 g of titania powder whilestirring. The samples were dried in static air at 120 C for 2 h followedby heating to 500 C (at 50 C min−1) and maintained at thistemperature for 3 h. The resulting catalysts have surface areas ofapproximately 52 m2 g−1 with TEM showing palladium particlesof sizes of∼2–4 nm (see Section 4). After calcination XPS showedthe surface Cl concentration to be <0.1percent. XP spectra were recordedwith a Kratos Axis Ultra-DLD photoelectron spectrometer using amonochromatic Al K X-ray source. The reactor consists of a stainlesssteel U-tube (6 mm o.d., 4 mm i.d.) mounted vertically in anoven that can be held at constant temperature or ramped in temperatureat a constant rate. The catalyst (0.5 g) was loaded intothe reactor tube and pre-treated in flowing helium (99.5percent purity,BOC Ltd) at 400 C for 40 min in order to remove unwanted carbonor oxygen containing species, confirmed by subsequent TPDin He, which shows no products evolving from the surface. Liquidreactants (methanol, ethanol, n-propanol and i-propanol, all99.8percent pure) were injected in 0.5 L injections through a septumassembly and they passed over the sample in well defined pulsesuntil the surface was saturated. The composition of the gas flowafter reaction with the catalyst is monitored by mass spectrometry(Hiden Analytical quadrupole (HAL 201)). Saturation of a samplewas defined as the point where no adsorption of reactant on thecatalyst could be detected from a pulse. For the temperature programmeddesorption (TPD) experiments the catalyst was exposedto the adsorbate until saturation, the temperature was then rampedat ∼1 C s−1 and the desorbing molecules monitored by mass spectrometry.Elucidation of the various products was made by use ofthe cracking patterns, and of the contribution of fragments to thevarious peaks in the TPD. For instance, a mass of 28 alone in a peakwith no mass 27 indicates CO desorption, whereas desorption ofmass 16 with coincident 15 and no higher masses is an indicationof methane desorption. With Titanium(IV) oxide, T= 400 °C Bahruji, Hasliza; Bowker, Michael; Brookes, Catherine; Davies, Philip R.; Wawata, Ibrahim; Applied Catalysis A: General; vol. 454; (2013); p. 66 - 73 View in Reaxys Dehydration Performance Evaluation. The catalytic performance of the catalysts was evaluated in a home-made,continuous flow fixed bed reactor (length 350 mm, inner diameter 9 mm) under atmospheric pressure. The catalyst (2g) was placed the middle of the reactor, and nitrogen gas was fed into the reactor for 30 min. The feedstock was introduced by a pulse micro-liquid pump with a weight hourly space velocity (WHSV) of 2.2 h1 into the evaporator and the reactor. The evaporator temperature was kept at 170 °C,the reactor temperature was increased from 210 °C to 420°C. The gas phase products were analyzed by a GC (Agilent6890) linked a TCD detector at an oven temperature of 90°C with Ar as carrier gas. The liquid phase products were analyzed by another GC (Agilent 6820) linked a FIDdetector in a temperature-programmed course from 40 °C to100 °C with N2 as carrier gas. The conversion of ethanol(Cethanol) is defined as the molar ratio of conversion ethanolto the total injection ethanol. The ethylene selectivity(Sethylene) and the diethyl ether selectivity (SDEE) are defined as the molar ratio of ethylene and diethyl ether to the total conversion ethanol, respectively. With TiO2NT supported ZSM-5 zeolite in neat (no solvent, gas phase), T= 420 °C , p= 760.051Torr , Temperature Wu, Liangpeng; Li, Xinjun; Yuan, Zhenhong; Chen, Yong; Bulletin of the Korean Chemical Society; vol. 35; nb. 2; (2014); p. 525 - 530 View in Reaxys

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With pyridine, Catalox® SCFa-140 gamma-alumina in water, T= 349.84 °C , p= 0.375038Torr , Kinetics, Pressure DeWilde, Joseph F.; Czopinski, Christopher J.; Bhan, Aditya; ACS Catalysis; vol. 4; nb. 12; (2014); p. 4425 4433 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. , T= 249.84 °C , p= 760.051Torr , Inert atmosphere, Reagent/catalyst, Temperature Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. With WO3 supported on sulphate containing zirconia, T= 199.84 °C , p= 760.051Torr , Inert atmosphere, Catalytic behavior, Reagent/catalyst, Temperature Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys 5 : Catalyst Evaluation General procedure: The above catalysts were prepared and evaluated. γ-Aluminum oxide, zirconium oxide without any metal coating were evaluated under the same testing conditions to serve as control. A fixed bed gas flow catalytic reactor was used as a reactor. 3 ml of the catalysts was filled in a stainless steel tube reactor with a diameter of 0.95 cm. As a pretreatment, hydrogen reduction was conducted for 1 hour under a carrier gas atmosphere (10percent H2/N2 base; flow rate 125 ml/min) at 400° C. After the pretreatment, the testing was conducted at a temperature between 250° C. and 325° C. and pressure between 1 kPa and 5,100 kPa, nitrogen flow rate was at 125 sccm and ethanol flow rate was at 0.2 ml/min. The reaction duration ranges from 5 hours to 80 hours. With γ-alumina, hydrogen, T= 290 °C , p= 25502.6Torr , Flow reactor, Inert atmosphere, Reagent/catalyst, Temperature Patent; Celanese International Corporation; Zhang, Cheng; Balliet, Kenneth; Johnston, Victor J.; US9024090; (2015); (B2) English View in Reaxys With rhabdophane, T= 290 - 360 °C , Inert atmosphere, Reagent/catalyst Afanasiev, Pavel; RSC Advances; vol. 5; nb. 53; (2015); p. 42448 - 42454 View in Reaxys With phosphomolybdic acid pillared interlayer clay, T= 300 °C , Reagent/catalyst Xie, Xianmei; Li, Zheng; Li, Baoru; Wu, Xu; An, Xia; RSC Advances; vol. 5; nb. 57; (2015); p. 46316 - 46324 View in Reaxys With sodium montmorillonite, T= 200 °C Xie, Xianmei; Li, Zheng; Li, Baoru; Wu, Xu; An, Xia; RSC Advances; vol. 5; nb. 57; (2015); p. 46316 - 46324 View in Reaxys With HMCM22, T= 199.84 °C , Reagent/catalyst

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Sad; Duarte; Padr; Apestegua; Applied Catalysis A: General; vol. 486; (2014); p. 77 - 84 View in Reaxys With HMCM22, T= 249.84 °C , Reagent/catalyst Sad; Duarte; Padr; Apestegua; Applied Catalysis A: General; vol. 486; (2014); p. 77 - 84 View in Reaxys Stage 1: With Cu/SiO2, Gas phase Stage 2:Catalytic behavior, Reagent/catalyst Klein, Alexander; Keisers, Kristina; Palkovits, Regina; Applied Catalysis A: General; vol. 514; (2016); p. 192 202 View in Reaxys O

Heavy Ends OH

Light Ends Permanent Gases

Rx-ID: 23141736 View in Reaxys 8/630 Yield

Conditions & References 2 : Example 2 A simulation of a reactor used for the manufacture of ethyl acetate (EtAc) yielded the following data for the inlet to the adiabatic catalyst bed, the outlet to the catalyst bed and the reactor outlet after the addition of 5153 kg/hr acetic acid (AcOH) (at 25° C.) and 302 kg/hr water (at 40° C.). The molar ratio of ethylene to acetic acid was 12:1 at the inlet and was returned to 12:1 at the outlet to the reactor following reaction; this Example shows how this may be achieved whilst simultaneously lowering the temperature attained at the catalyst bed outlet. It should be noted that the reduction in temperature produced by the simulation is achieved by liquid injection alone and without making use of relatively expensive heat exchangers.[TABLE-US-00003] Inlet to Outlet to After AcOH Catalyst Catalyst water Stream Bed (kg/hr) Bed (kg/hr) Injection (kg/hr) Acetic Acid 36355 30586 35738 Ethylene 202680 199967 199967 EtAc 7111 15576 15576 Ether 1404 1431 1431 Water 8196 8189 8492 Ethanol 1656 1656 1656 Light Ends 22440 22440 22440 Permanent Gases Heavy Ends 6.3 6.3 6.3 TOTAL 279848 279851 285307 Pressure 1200 (11) 1200 (11) 1200 (11) (KPa (barg)) Temperature 175.0 183.3 175.0 (° C.) Phase Vapour Vapour Vapour With water, silicotungstic acid / SiO2, T= 175 °C , p= 9000.9Torr , Gas phase, Industry scale Patent; BP Chemicals Limited; US2004/167353; (2004); (A1) English View in Reaxys 3 : Example 3 A simulation of a reactor used for the manufacture of ethyl acetate (EtAc) yielded the following data for the inlet to the adiabatic catalyst bed, the outlet to the catalyst bed and the reactor outlet after the addition of 5075 kg/hr acetic acid (AcOH) (at 25° C.). The molar ratio of ethylene to acetic acid was 12:1 at the inlet and 11.7:1 at the outlet to the reactor and thus this Example shows how this ratio may be maintained within the preferred range whilst simultaneously lowering the temperature attained at the catalyst bed outlet. It should be noted that the reduction in temperature produced by the simulation is achieved by liquid injection alone and without making use of relatively expensive heat exchangers. [TABLE-US-00004] Inlet to Outlet to After AcOH Catalyst Catalyst Injection Stream Bed (kg/hr) Bed (kg/hr) (kg/hr) Acetic Acid 30296 25488 30563 Ethylene 168900 166639 166639 EtAc 5926 12980 12980 Ether 1170 1193 1193 Water 6830 6825 6825 Ethanol 1380 1380 1380 Light Ends 18700 18700 18700 Permanent Gases Heavy Ends 5.3 5.3 5.3 TOTAL 233207 233209 238285 Pressure 1200 (11) 1200 (11) 1200 (11) (KPa (barg)) Temperature 175.0 183.3 175.0 (° C.) Phase Vapour Vapour Vapour With water, silicotungstic acid / SiO2, T= 175 °C , p= 9000.9Torr , Gas phase, Industry scale Patent; BP Chemicals Limited; US2004/167353; (2004); (A1) English View in Reaxys

Rx-ID: 23051291 View in Reaxys 9/630

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Yield

Conditions & References

91.8 %, 4.3 %, 3.5 %

4 : Example 4 The catalyst used was the same as used in Example 1. Using the reactor shown in Fig. 1, ethylene, nitrogen, acrylic acid and water were fed in a molar ratio of 80.0:10.3:6.7:3.0 from the respective inlets at a space velocity of 1,500 hr-1 under a pressure of 0.3 MPa. Nitrogen was fed together with ethylene and water was fed together with acrylic acid. In this case, the temperature at which the acrylic acid-water mixture vaporized was 85.6°C. When the reaction system was heated so that the catalyst layer had a peak temperature of 165°C, the reaction results were such that the STY of ethyl acrylate was 52 g/l-cat.bul.h and the selectivities of ethyl acrylate, ethanol and diethyl ether were 91.8percent, 4.3percent and 3.5percent, respectively. With water, cesium nitrate; tungstophosphoric acid; water; mixture of, dried, tabletted, T= 85.6 - 165 °C , p= 2250.23Torr , Gas phase, Product distribution / selectivity Patent; SHOWA, DENKO K.K.; EP1218331; (2004); (B1) English View in Reaxys

O OH

Rx-ID: 24653100 View in Reaxys 10/630 Yield

Conditions & References

81%

45.1 : Preparation of 2-hydroxy-3-[(4-phenyl)phenoxy]propanohydroxamic acid Step 1: 1,1-Dimethoxy-2-(4-biphenyloxy)ethane. 4-Phenylphenol (1.70 g, 10 mmol) and cesium carbonate (3.91 g (12 mmol) were stirred at room temperature under a nitrogen atmosphere in 20 mL of dimethylformamide until it appeared that no more solid was dissolving. At that point, 1.42 mL (12 mmol) of bromoacetaldehyde dimethyl acetal (2.03 g, 12 mmol) were added to the mixture via syringe and the resulting brown suspension was stirred at room temperature overnight. The mixture was then heated under reflux for two hours and then stirred at room temperature overnight. At the end of this period, 100 mL of water and 200 mL of diethyl ether were added; the organics were extracted into the ether layer, which was separated, dried over anhydrous sodium sulfate and evaporated to yield 2.10 g (81percent yield) of dimethoxy-2-(4-biphenyloxy)ethane. With caesium carbonate in N-methyl-acetamide Patent; Abbott Laboratories; US5665777; (1997); (A1) English View in Reaxys O

O O

Rx-ID: 38013411 View in Reaxys 11/630 Yield

Conditions & References The catalytic behavior of synthesized resins in the reaction between OcOH and DEC to form EOE is gathered in Table 4. After 6 h, DEC conversions ranged from 13.3percent to 37.0percent and OcOH conversions from 11.2percent to 28.7percent. By comparing both reaction systems, it is observed that OcOH conversions were higher in the reaction with DEC than with EtOH, in agreement with the open literature [11]. Such behavior can be explained by the affinity of reactants to sulfonated resins. The number of moles retained in the swollen resin follows this trend: EtOH > OcOH >> DEC, in accordance with their polarity [11,26]. In the OcOH/EtOH mixture, there is a higher amount EtOH than OcOH inside the resin, which favors EtOH conversion. On the other hand, in the OcOH/DEC mixture the liquid inside the resin is predominantly OcOH, however, the amounts of DEC are large enough to the reaction take place with similar DEC and OcOH conversions except on the highly sulfonated resins. Fig. 10 shows the OcOH and DEC conversions as the relative values compared to the most active catalyst, Amberlyst 15. DEC relative conversion increased linearly as a function of the acid capacityof resins. This conversion pattern is similar to that observed for EtOH in the EtOH/OcOH system. Thus, it can be concluded that all the acid centers were accessible for both ethylating agents, DEC and EtOH. As for OcOH conversion, its dependence on the number of acid groups is much higher over the low sulfonated resins (62 mmol H+/g) than that observed in the high sulfonated ones. The formation of ethers from carbonates proceeds in two consecutive steps and intermediate compounds are involved. As seen in Table 4, selectivity to DEE increased as the acid capacity of the catalysts increased, whereas the selectivity to EOE reaction pathway (EOC + EOE) decreased. Fig. 11 displays the moles of products formed in the OcOH/DEC reaction system. For the sake of clarity, the intermediate compounds were plotted together with their ultimate corresponding

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ether, since at long reaction times all EOC would be consumed to form EOE, and in the same way, DOC to form DNOE [11]. Thus, EOC, which would decompose to EOE at alonger reaction time was plotted jointly with EOE. Likewise, DOC and DNOE were plotted jointly. In this way, the formation of DEE, EOE and DNOE were displayed as competitive reactions, analogously to the EtOH/OcOH reaction system. As seen, DEE formation was highly increased in the more sulfonated catalysts, as a result of steric hindrances of EOE formation. However, the EOE reaction pathway was more favored than the DEE formation on all the catalysts tested. As for DNOE formation, the ether with the highest molecular weight, the number of moles of produced ether was low over all the tested catalysts due to the highest sterical hindrances. In addition, selectivity to DNOE pathway (DOC + DNOE) was also decreased at the highest sulfonation degrees. On the view of Fig. 11 it can be concluded that despite high fuctionalized resins are more suitable in the DEC/OcOH system than in the EtOH/OcOH system, from the standpoint of the industrial use a catalyst with more than 3 mmol H+/g is not potentially attractive for EOE synthesis because with higher sulfonation degrees DEE formation is already noticeable. With Amberlyst 15, Time= 6h, T= 150 °C , p= 18751.9Torr Guilera, Jordi; Hankova, Libuse; Jerabek, Karel; Ramirez, Eliana; Tejero, Javier; Reactive and Functional Polymers; vol. 78; nb. 1; (2014); p. 14 - 22 View in Reaxys

O NH 2

H N

O O

N N

O O

Rx-ID: 23573582 View in Reaxys 12/630 Yield

Conditions & References 5 :The purpose of this experiment is demonstrating the production of diethyl carbonate (DEC). DEC was produced by reacting ethyl carbamate (EC) with ethanol. The experiment was carried out in the similar manner to the Example 2. An ethyl carbamate solution in ethanol and ethanol were used in place of MC solution and methanol respectively in Example 2. The reboiler of the distillation column was loaded with the following materials; 180 grams of triglyme, 100 grams of ethanol and 100 grams of dibutyltin dimethoxide. A steady state operation of the distillation column reactor was obtained, while pumping in an ethyl carbamate (EC) solution at a constant flow rate and adjusting the ethanol pumping rate to maintain a constant temperature of the liquid reaction medium. The reactor operation was continued for 340 hours without interruption at 345° F. of the liquid reaction medium in the reboiler, the distillation column temperature of 282° F., and a constant overhead pressure of 66 psig with an autoclave stirring rate of 300 rpm. The pumping rate of a 15.35 wt. percent EC solution (275 ppm H2O) was fixed at 2.69 ml/min and the average pumping rate of ethanol (106 ppm H2O) was 2.36 ml/min. The overhead vapor stream at the top of the column was mixed with nitrogen dilution gas (600 cc/min) and then cooled to about 200° F. in a water cooled condenser. The average compositions of the overhead products and the composition of the bottom products for the entire run are listed in Table 3. 74.2 grams of solid material were removed from the reactor at the end run, which was a mixture of heterocyclic compounds and contained 670 ppm Sn by weight. The analysis of the bottom product in Table 3 indicates that the mole ratio of EC/C2H5OH and DEC wt. percent based on EC and ethanol in the liquid medium in the reactor was 0.939 and 11.08 wt. percent respectively. The mass balance and urea mole balance for the entire run were 102percent and 101percent, respectively. The run result indicates 57.5percent conversion of EC and 91 mole percent selectivity of EC to DEC. The experimental result translates to DEC space yield of 1.60 lb/h/ft3. With di-n-butyltin dimethoxide in triglyme (triethylene glycol dimethyl ether), Time= 340h, T= 173.879 °C , p= 4173.32Torr Patent; CATALYTIC DISTILLATION TECHNOLOGIES; US2005/203307; (2005); (A1) English View in Reaxys

Rx-ID: 35870596 View in Reaxys 13/630

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Yield

Conditions & References General procedure: ExperimentalThe catalytic hydrogenation of AA (96percent, from Reanal) (modelcompound with the shortest aliphatic chain) was studied in ahigh-pressure fixed bed flow-through reactor at 21 bar total pres-sure, 240–380C, 7–21 bar hydrogen and 0.5–3.5 bar acetic acidpartial pressures, i.e., under similar conditions as in Refs. [10,21].The Fischer esterification of AA and ethanol (absolute, from MolarChemical) and ethylacetate (>99percent, from Merck) hydrogenationwere also studied over the investigated catalyst samples to followthe secondary reactions. The experimental setup is illustrated inFig. 1. In general, the catalysts were pretreated in hydrogen flowin situ in the reactor at 450C and 21 bar for 1 h in order to obtainactive metallic surfaces for carboxylic acid reduction. The reactionwas allowed to run one hour at each condition to attain steadystate. Before sampling, the effluent during the second hour wascollected, depressurized and cooled to room temperature. The liq-uid product mixture at ambient conditions was analyzed by gaschromatograph (Shimadzu 2010) for AA products equipped with aRestek Rt-UBOND capillary column, and a flame ionization detec-tor. The gaseous reactor effluent was analyzed for CO2, CO, CH4andlight hydrocarbons using an on-line gas chromatograph (HP-5890)having Carboxen 1006 PLOT capillary column and thermal conduc-tivity detector (TCD). The results are represented as stacked areagraphs where the distance between two neighboring curves repre-sents the concentration of a given product at a given temperaturein mole percent With hydrogen, T= 240 - 280 °C , p= 15751.6Torr , Flow reactor, Reagent/catalyst Onyestyak, Gyoergy; Harnos, Szabolcs; Klebert, Szilvia; Stolcova, Magdalena; Kaszonyi, Alexander; Kallo, Denes; Applied Catalysis A: General; vol. 464-465; (2013); p. 313 - 321 View in Reaxys OH

Rx-ID: 39883716 View in Reaxys 14/630 Yield

Rx-ID: 1878332 View in Reaxys 15/630 Yield 75.4 %

Conditions & References With aluminum oxide, carbon dioxide, T= 314 °C , p= 141764Torr Parrott, Andrew J.; Bourne, Richard A.; Akien, Geoffrey R.; Irvine, Derek J.; Poliakoff, Martyn; Angewandte Chemie - International Edition; vol. 50; nb. 16; (2011); p. 3788 - 3792 View in Reaxys With Nb-dimer, silica gel, T= 249.9 °C , p= 24.8Torr , var. temp. and Nb/SiO2 catalysts, Product distribution Ichikuni, Nobuyuki; Asakura, Kiyotaka; Iwasawa, Yasuhiro; Journal of the Chemical Society, Chemical Communications; nb. 2; (1991); p. 112 - 113 View in Reaxys p= 8.3Torr , effect of the activities and selectivities of (one-atomic niobium oxide and imperg.niobium oxide, Nb2O5 as catalyst) on dehydration, Kinetics Asakura, Kiyotaka; Twasawa, Yasuhiro; Chemistry Letters; (1986); p. 859 - 862 View in Reaxys

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With niobium, T= 249.9 °C , p= 23.3Torr , other Nb catalysts, other temperatures, Product distribution, Rate constant Nishimura, M.; Asakura, K.; Iwasawa, Y.; Journal of the Chemical Society, Chemical Communications; nb. 22; (1986); p. 1660 - 1661 View in Reaxys With molybdenum(VI) oxide, T= 215 °C , p= 760Torr , also with O2 at 291 deg C, Mechanism, Product distribution Tatibouet, Jean-Michel; Germain, Jean-Eugene; Journal of Chemical Research, Miniprint; nb. 9; (1981); p. 3070 3080 View in Reaxys With H4SiW12O40, polyaniline, T= 240 °C , other heteropolyacids, other supports, var. temp, Product distribution Bielanski, A.; Pozniczek, J.; Malecka, A.; Bulletin of the Polish Academy of Sciences, Chemistry; vol. 45; nb. 1; (1997); p. 41 - 52 View in Reaxys With Al-Mg-O, Time= 5h, T= 500 °C , Product distribution, Further Variations: Temperatures, Catalysts Abd El-Raady, Ahmed A.; Fouad, Nasr E.; Mohamed, Mohamed A.; Halawy, Samih A.; Monatshefte fur Chemie; vol. 133; nb. 10; (2002); p. 1351 - 1361 View in Reaxys 13.8 %Chromat., 54.9 %Chromat., 7.3 %Chromat.

6.2 :Example 6Quartz wool was packed on the bottom of a heat resistant glass reactor of an inner diameter of 10 mm, and a predetermined amount of the catalyst was charged thereon. A fine glass tube for inserting a thermoelectric couple was put in the center of the reaction tube to measure the temperature, and the height of the quartz wool was so adjusted that a tip of the thermoelectric couple was positioned at the center. The reaction apparatus was constituted by a mass flow controller, a micro feeder, a reaction tube and a gas chromatography (with a hydrogen flame detector) for analysis. The reaction gas was the one obtained by introducing the ethyl alcohol through the micro feeder into carrier gas of which the flow rate was controlled by the mass flow meter, and was introduced from above the catalyst layer so as to flow downward thereof to be brought to a gas sampler for gas chromatography. The reaction tube was heated by an electric furnace so that the catalyst layer assumed a predetermined temperature. Prior to the reaction, the catalyst was pre-treated by flowing nitrogen gas at a rate of 50 mL/min. at 673K for 2 hours. The reaction was conducted by feeding mixed gas (containing 5.5percent by volume of ethyl alcohol) of ethyl alcohol and nitrogen at a rate of 10 mL/min. The pressure was 0.1 MPa.Table 1 shows the results of the thus conducted reaction. In Table 1, "Butene" stands for a mixture of 1-butene and 2-butene, "Ethanol conversion (percent)" stands for a percentage of the mol number of ethyl alcohol that has reacted to the mol number of ethyl alcohol before reacted, and "Selectivity coefficient (percent)" stands for a percentage of the mol number of the component calculated as the ethyl alcohol to the mol number of the reacted ethyl alcohol. The same also holds true in Tables 2 to 5 appearing later. With Ni on C12-MCM-41, T= 523 °C , p= 750.075Torr , Gas phase, Inert atmosphere Patent; Iwamoto, Masakazu; Yamamoto, Takashi; Haishi, Teruki; US2010/168491; (2010); (A1) English View in Reaxys With oxygen, T= 400 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys With water, T= 299.84 °C , Flow reactor, Inert atmosphere, Catalytic behavior Riani, Paola; Garbarino, Gabriella; Lucchini, Mattia Alberto; Canepa, Fabio; Busca, Guido; Journal of Molecular Catalysis A: Chemical; vol. 383-384; (2014); p. 10 - 16 View in Reaxys With water, T= 399.84 °C , Flow reactor, Inert atmosphere, Catalytic behavior Riani, Paola; Garbarino, Gabriella; Lucchini, Mattia Alberto; Canepa, Fabio; Busca, Guido; Journal of Molecular Catalysis A: Chemical; vol. 383-384; (2014); p. 10 - 16 View in Reaxys With silica gel, T= 399.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor

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Janssens, Wout; Makshina, Ekaterina V.; Vanelderen, Pieter; De Clippel, Filip; Houthoofd, Kristof; Kerkhofs, Stef; Martens, Johan A.; Jacobs, Pierre A.; Sels, Bert F.; ChemSusChem; vol. 8; nb. 6; (2015); p. 994 - 1008 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. With WO3 suppored on MgO–Al2O3, T= 349.84 °C , p= 760.051Torr , Inert atmosphere, Reagent/catalyst, Temperature Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. With WO3 suppored on MgO–Al2O3, T= 399.84 °C , p= 760.051Torr , Inert atmosphere, Reagent/catalyst, Temperature Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys With sulfated zirconia ceramic foam, T= 150 - 300 °C , p= 760.051Torr , Gas phase Alves-Rosa, Marinalva A.; Martins, Leandro; Hammer, Peter; Pulcinelli, Sandra H.; Santilli, Celso V.; RSC Advances; vol. 6; nb. 8; (2016); p. 6686 - 6694 View in Reaxys With [Al(OH)(m-BDC-H)0.76(m-BDC-SO3H)0.24]· 1.5H2O·0.2DMF, T= 250 - 300 °C , Inert atmosphere, Catalytic behavior, Kinetics, Reagent/catalyst, Temperature Reimer, Nele; Bueken, Bart; Leubner, Sebastian; Seidler, Christopher; Wark, Michael; De Vos, Dirk; Stock, Norbert; Chemistry - A European Journal; vol. 21; nb. 35; (2015); p. 12517 - 12524 View in Reaxys

Si O

Rx-ID: 23047465 View in Reaxys 16/630 Yield 96.3 %, 5.9 %

Conditions & References 17 : Example 17; Catalytic Hydrosilylation of an Ester This example is similar to Example 15, except that hydrosilylation of an ester required 2 equivalents of HSiEt3 per 1 equivalent of substrate. In a glove box, CpW(CO)2(IMes)+B(C6F5)4- (2.8 mg, 0.002 mmol), ethyl acetate (98 μL, 1.00 mmol), HSiEt3 (352 μL, 2.20 mmol), and two sealed capillaries with C6D6 were placed in an NMR tube equipped with a teflon valve. The reaction was carried out at 23 C. At high conversions the polarity of the medium drastically decreased. A light purple precipitate was formed and solution turned colorless. After 18 minutes, TON(alkoxysilane) was 52 and TON(ether) was 0. After 26 hours, TON(alkoxysilane) was 468 and TON(ether) was 30, representing a total of 100percent conversion of the initial ester. With triethylsilane, [CpW(CO)2(1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene)]B(C6F5)4, Time= 26h, T= 23 °C , Conversion of starting material Patent; Brookhaven Science Associates, LLC; US6737531; (2004); (B1) English

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View in Reaxys

Rx-ID: 40205338 View in Reaxys 17/630 Yield

Conditions & References After heating the catalysts, the conversion of ethanol was carried outin a continuous-flow reactor under atmospheric pressure at 673 K. Ethanol was continuously delivered by a syringe infusion micro pump to a preheating zone of the reactor containing quartz sand, where it would be vaporized. The contact time (W/F) was 5.49 g h mol−1, where W is the weight of the catalyst (g) and F is the total flow rate (mol h−1). The pressure of ethanol was 101.3 kPa. With zinc-containing talc in neat (no solvent), T= 399.84 °C , Reagent/catalyst Sekiguchi, Yasumasa; Akiyama, Sohta; Urakawa, Wataru; Koyama, To-Ru; Miyaji, Akimitsu; Motokura, Ken; Baba, Toshihide; Catalysis Communications; vol. 68; (2015); p. 20 - 24 View in Reaxys

Rx-ID: 40975854 View in Reaxys 18/630 Yield

Rx-ID: 23251472 View in Reaxys 19/630 Yield 0.3 %, 5.3 %, 0.1 %, 7.7 %, 1.9 %

Conditions & References D : Comparative Example D This experiment demonstrates the reaction of methanol with carbon monoxide in the presence of hydrogen by a rhodium catalyst in the presence of dppp and a ruthenium promoter during a 30 min run time. A mixture of hydrogen and carbon at a H2 : CO ratio of 2: 1 was used. In this experiment the phosphine-rhodium complex was generated in situ. 1. 114 gram of dppp was placed in a portion of the methanol charge (ca. 60g) with 0.658 gram of (acac) Rh (CO) 2 to form a catalyst precursor suspension. 2.590 gram of RUCL3. 3H20 was placed in the autoclave together with approximately 5 gram of methanol and the autoclave was pressure tested. The MeI co-catalyst was added to the autoclave, followed by the catalyst precursor suspension. The remaining methanol was added and the autoclave was pressurised with syngas (approximately 20 barg). The experiment was then conducted as for Comparative Example C. Charge composition data and reaction conditions are shown in Tables 3a and 3b respectively. The product distribution and product selectivity data obtained is given in Tables 4 and 5 respectively. With carbon monoxide, 1,3-bis-(diphenylphosphino)propane, hydrogen, ruthenium trichloride, (acac)Rh(CO)2, methyl iodide in water, Time= 0.5h, T= 140 °C , p= 50255Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101488; (2004); (A1) English View in Reaxys

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-1 F

F F FF F

O+

F F

(v6) F F F

F F

F P–

C+

F F F

Rx-ID: 28129753 View in Reaxys 20/630 Yield

Conditions & References

93.6 %

18 :Example 18Tritylium tris(pentafluoroethyl)trifluorophosphate A mixture of 1.12 g (4.02 mmol) of tritylium chloride and 2.20 g (4.02 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 70-80° C. (temperature of the oil bath) and stirred for ten hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 70° C. (temperature of the oil bath), giving 2.59 g of a solid. The yield of tritylium tris(pentafluoroethyl)trifluorophosphate is 93.6percent. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 7.18-740 m (3C6H5);19F NMR spectrum, ppm: -43.65 dm (PF), -79.69 m (CF3), -81.39 m (2CF3), -87.07 dm (PF2), -115.14 dm (CF2), -115.68 dm (2CF2); J1 P,F=891 Hz, J1 P,F=902

Hz, J2 P,F=87 Hz, J2 P,F=105 Hz.

, Time= 10h, T= 80 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys

F N–

S O

O+

Cl –

N+

F F

O O S F

N–

O S

F F

N+ N

Rx-ID: 28129755 View in Reaxys 21/630 Yield

Conditions & References

97.9 %

15 :A mixture of 1.32 g (9.0 mmol) of 1-ethyl-3-methylimidazolium chloride and 3.45 g (9.0 mmol) of triethyloxonium bis(trifluoromethylsulfonyl)imide from Example 3 is heated to 70-80° C. (temperature of the oil bath) and stirred for four hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 70° C. (temperature of the oil bath), giving 3.45 g of a liquid. The yield of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide is 97.9percent, based on the 1-ethyl-3-methylimidazolium chloride employed. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 1.45 t (CH3); 3.83 s (CH3); 4.17 q (CH2); 7.37 m (CH); 7.43 m (CH); 8.57 br. s. (CH); 3JH,H=7.3 Hz.19F NMR spectrum, ppm: -78.91 s (CF3). , Time= 3h, T= 80 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys

F F

F F FF F F

F P–

F F F FF F

O+

Cl –

F F

N N+

F F

F FF

F F

F F F F

P– F F F F

F N+ N

Rx-ID: 28129761 View in Reaxys 22/630

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Yield

Conditions & References

96 %

19 :Example 191-Decyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate A mixture of 0.34 g (1.31 mmol) of 1-decyl-3-methylimidazolium chloride and 0.72 g (1.31 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 80° C. (temperature of the oil bath) and stirred for three hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 80° C. (temperature of the oil bath), giving 0.84 g of a liquid. The yield of 1-decyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate is 96percent. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 0.90 m (CH3), 1.30 m (7CH2), 1.82 m (CH2), 3.82 s (CH3), 4.11 t (CH2), 7.32 d,d (CH), 7.36 d,d (CH), 8.37 m (CH); J3 H,H=7.4

Hz, J4 H,H=1.8 Hz.19F NMR spectrum, ppm: -43.61 dm (PF), -79.65 m (CF3), -81.34 m (2CF3), -87.07 dm

(PF2), -115.09 dm (CF2), -115.61 dm (2CF2); J1 P,F=891 Hz, J1 P,F=906 Hz, J2 P,F=83 Hz, J2 P,F=105 Hz.31P NMR spectrum, ppm: -148.1 d,t,m. , Time= 3h, T= 80 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys F

-1 F

F F FF F

F P–

F F FF F

N+

O+

Cl –

(v6)

F F

F FF

F F F F

F N

C+

Rx-ID: 28129762 View in Reaxys 23/630 Yield

Conditions & References

98.9 %

13 :Example 13Hexamethylguanidinium tris(pentafluoroethyl)trifluorophosphate A mixture of 1.81 g (10.07 mmol) of hexamethylguanidinium chloride and 5.53 g (10.09 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 70-80° C. (temperature of the oil bath) and stirred for three hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 70° C. (temperature of the oil bath), giving 5.88 g of a solid. The yield of hexamethylguanidinium tris(pentafluoroethyl)trifluorophosphate is 98.9percent, based on the hexamethylguanidinium chloride employed. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 2.89 s (6CH3).19F NMR spectrum, ppm: -43.63 dm (PF), -79.68 m (CF3), -81.37 m (2CF3), -87.05 dm (PF2), -115.07 dm (CF2), -115.64 dm (2CF2); J1 P,F=891 Hz, J1 P,F=906 Hz, J2 P,F=84

Hz, J2 P,F =105 Hz.31P NMR spectrum, ppm: -149.0 d,t,m.

, Time= 3h, T= 80 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys N

F F

F F FF F F

F P–

F F FF F

O+

N+ Br–

F F

F F F F F

P–

F F F F F

N+

F F

Rx-ID: 28129766 View in Reaxys 24/630 Yield 93.2 %

Conditions & References 9 :Example 91-Cyano-4-dimethylaminopyridinium tris(pentafluoroethyl)trifluorophosphate A mixture of 5.93 g (25.90 mmol) of 1-cyano-4-dimethylaminopyridinium bromide and 14.30 g (26.09 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 60° C. (temperature of the oil bath) and stirred for five hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 50° C. (temperature of the oil bath), giving 14.32 g of a solid. The yield of 1-cyano-4-dimethylaminopyridinium tris(pentafluoroethyl)trifluorophosphate is 93.2percent, based on the 1-cyano-4-dimethylaminopyridinium bromide employed. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 3.34 s (2CH3), 6.99 d (CH), 7.03 d (CH), 8.04 d (CH), 8.20 d (CH); J3 H,H=8.2 Hz.19F NMR spectrum, ppm: -43.57 dm (PF), -79.60 m (CF3), -81.30 m (2CF3), -87.00 dm (PF2), -115.05 dm (CF2), -115.60 dm (2CF2); J1 P,F=889 Hz, J1 P,F=906 Hz, J2 P,F=81 Hz, J2 P,F=107 Hz.

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, Time= 5h, T= 60 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys N

F S

N– O

N+

O+

Br–

F S

N– O

N+

O N

Rx-ID: 28129767 View in Reaxys 25/630 Yield

Conditions & References

98.2 %

14 :Example 141-Cyano-4-dimethylaminopyridinium bis(trifluoromethylsulfonyl)imide A mixture of 5.22 g (22.89 mmol) of 1-cyano-4-dimethylaminopyridinium bromide and 8.77 g (22.88 mmol) of triethyloxonium bis(trifluoromethylsulfonyl)imide from Example 3 is heated to 60° C. (temperature of the oil bath) and stirred for five hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 50° C. (temperature of the oil bath), giving 14.32 g of a solid. The yield of 1-cyano-4-dimethylaminopyridinium bis(trifluoromethylsulfonyl)imide is 98.2percent, based on the 1-cyano-4-dimethylaminopyridinium bromide employed. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 3.34 s (2CH3), 6.99 d (CH), 7.03 d (CH), 8.04 d (CH), 8.19 d (CH); J3 H,H=8.2 Hz.19F NMR spectrum, ppm: -78.96 s. , Time= 5h, T= 60 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys F

N+

F F

Cl –

FF F F

F P–

F F F FF F

O+

F F

F FF

F F

F F F F

P– F F F F

F N+

Rx-ID: 28129768 View in Reaxys 26/630 Yield

Conditions & References

93 %

20 :Example 201-Hexyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate A mixture of 0.20 g (0.97 mmol) of 1-hexyl-1-methylpyrrolidinium chloride and 0.53 g (0.97 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 80° C. (temperature of the oil bath) and stirred for three hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 80° C. (temperature of the oil bath), giving 0.55 g of a liquid. The yield of 1-hexyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate is 93percent. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 0.92 m (CH3), 1.35 m (3CH2), 1.74 m (CH2), 2.16 m (2CH2), 2.93 s (CH3), 3.18 m (CH2), 3.40 m (2CH2).19F NMR spectrum, ppm: -43.58 dm (PF), -79.64 m (CF3), -81.34 m (2CF3), -87.00 dm (PF2), -115.03 dm (CF2), -115.58 dm (2CF2); J1 P,F=891 Hz, J1 P,F=906 Hz, J2 P,F=84 Hz, J2 P,F=106 Hz.31P NMR spectrum, ppm: -148.1 d,t,m. , Time= 3h, T= 80 °C Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys O

Rx-ID: 29540487 View in Reaxys 27/630

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Yield

Conditions & References

13.8 %Chromat., 56.5 %Chromat., 7.1 %Chromat., 6.2 %Chromat.

6.3 :Example 6Quartz wool was packed on the bottom of a heat resistant glass reactor of an inner diameter of 10 mm, and a predetermined amount of the catalyst was charged thereon. A fine glass tube for inserting a thermoelectric couple was put in the center of the reaction tube to measure the temperature, and the height of the quartz wool was so adjusted that a tip of the thermoelectric couple was positioned at the center. The reaction apparatus was constituted by a mass flow controller, a micro feeder, a reaction tube and a gas chromatography (with a hydrogen flame detector) for analysis. The reaction gas was the one obtained by introducing the ethyl alcohol through the micro feeder into carrier gas of which the flow rate was controlled by the mass flow meter, and was introduced from above the catalyst layer so as to flow downward thereof to be brought to a gas sampler for gas chromatography. The reaction tube was heated by an electric furnace so that the catalyst layer assumed a predetermined temperature. Prior to the reaction, the catalyst was pre-treated by flowing nitrogen gas at a rate of 50 mL/min. at 673K for 2 hours. The reaction was conducted by feeding mixed gas (containing 5.5percent by volume of ethyl alcohol) of ethyl alcohol and nitrogen at a rate of 10 mL/min. The pressure was 0.1 MPa.Table 1 shows the results of the thus conducted reaction. In Table 1, "Butene" stands for a mixture of 1-butene and 2-butene, "Ethanol conversion (percent)" stands for a percentage of the mol number of ethyl alcohol that has reacted to the mol number of ethyl alcohol before reacted, and "Selectivity coefficient (percent)" stands for a percentage of the mol number of the component calculated as the ethyl alcohol to the mol number of the reacted ethyl alcohol. The same also holds true in Tables 2 to 5 appearing later. With Ni on C12-MCM-41, Time= 2h, T= 573 °C , p= 750.075Torr , Gas phase, Inert atmosphere Patent; Iwamoto, Masakazu; Yamamoto, Takashi; Haishi, Teruki; US2010/168491; (2010); (A1) English View in Reaxys

SiH

O Si

Rx-ID: 30072464 View in Reaxys 28/630 Yield

Conditions & References With {IrH(acetone)[2,6-(tBu2PO)2C6H3]}{BF4} in chlorobenzene-d5, Time= 0.3h, T= 20 °C , Inert atmosphere Park, Sehoon; Brookhart, Maurice; Organometallics; vol. 29; nb. 22; (2010); p. 6057 - 6064 View in Reaxys With [Ph3S][tBu2CarbCO2B(C6F5)3] in dichloromethane-d2, Time= 0.25h, T= 20 °C , UV-irradiation Khalimon, Andrey Y.; Piers, Warren E.; Blackwell, James M.; Michalak, David J.; Parvez, Masood; Journal of the American Chemical Society; vol. 134; nb. 23; (2012); p. 9601 - 9604 View in Reaxys

74 %Spectr., 26 %Spectr.

V-1 :General procedure: Hydrosilane was added in one portion at room temperature to a solution of substrate (0.25 mol/L) and 5 (1 mol percent to the substrate) in either CD2CI2 or CH2CI2. The resulting mixture was placed in either quartz NMR or quartz test tube under argon atmosphere. No reaction was observed in the absence of UV light within 1 hour at room temperature. For hydrosilylation reactions, the samples were exposedto 254 nm light for 15 mm. Conversion of organic substrates was determined by 1HNMR spectroscopy using Si(SiMe3)4 as a standard (Table 3). For silylation andPiers-Rubinsztajn reactions (Table 4), the samples were exposed to 254 nm light for15-45 mm and after that left at room temperature for 10 mm — 48 hours. Yields ofproducts were determined by NMR spectroscopy and in the case of monomericsubstrates were confirmed by GS-MS. With [Ph3S][tBu2CarbCO2B(C6F5)3], Time= 0.25h, T= 20 °C , UV-irradiation, Inert atmosphere Patent; UTI LIMITED PARTNERSHIP; PIERS, Warren Edward; KHALIMON, Andrey Yur'evich; VON MARWITZ, Adam John; WO2013/142956; (2013); (A1) English View in Reaxys

Rx-ID: 25673540 View in Reaxys 29/630

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Yield

Conditions & References

89 %, 4.0 %

2.19 :Example 2; Twelve grams of macroreticular strong acid ion-exchange resin and 57 grams ethanol were loaded in a 250 mL autoclave reactor. The autoclave was closed and heated to 125° C. A feed mixture consisting of 90 g furfuryl alcohol (43 mole percent), 55 g ethanol (56 mole percent) and 1.5 g (0.4 mole percent) of n-dodecane as internal standard was continuously fed to the autoclave under continuous stirring (1500 rpm). The temperature was maintained at 125° C. After addition of the whole feed mixture, the reactor was cooled and the liquid reaction mixture was analysed by gas chromatography. With Amberlyst 15, Time= 1.16667h, T= 125 °C , Conversion of starting material Patent; Van De Graaf, Wouter David; Lange, Jean-Paul; US2007/49771; (2007); (A1) English View in Reaxys

68 - 81 %, 2.17; 2.18 :Example 2; Twelve grams of macroreticular strong acid ion-exchange resin and 57 grams ethanol were 0.4 - 0.6 % loaded in a 250 mL autoclave reactor. The autoclave was closed and heated to 125° C. A feed mixture consisting of 90 g furfuryl alcohol (43 mole percent), 55 g ethanol (56 mole percent) and 1.5 g (0.4 mole percent) of n-dodecane as internal standard was continuously fed to the autoclave under continuous stirring (1500 rpm). The temperature was maintained at 125° C. After addition of the whole feed mixture, the reactor was cooled and the liquid reaction mixture was analysed by gas chromatography. With Amberlyst 46, Time= 0.55 - 1.1h, T= 125 °C , Conversion of starting material Patent; Van De Graaf, Wouter David; Lange, Jean-Paul; US2007/49771; (2007); (A1) English View in Reaxys 60 - 85 %, 2.20; 2.21 :Example 2; Twelve grams of macroreticular strong acid ion-exchange resin and 57 grams ethanol were 1.2 - 1.7 % loaded in a 250 mL autoclave reactor. The autoclave was closed and heated to 125° C. A feed mixture consisting of 90 g furfuryl alcohol (43 mole percent), 55 g ethanol (56 mole percent) and 1.5 g (0.4 mole percent) of n-dodecane as internal standard was continuously fed to the autoclave under continuous stirring (1500 rpm). The temperature was maintained at 125° C. After addition of the whole feed mixture, the reactor was cooled and the liquid reaction mixture was analysed by gas chromatography. With Amberlyst 36, Time= 0.533333 - 1.11667h, T= 125 °C , Conversion of starting material Patent; Van De Graaf, Wouter David; Lange, Jean-Paul; US2007/49771; (2007); (A1) English View in Reaxys 38 - 85 %, 2.22; 2.23 :Example 2; Twelve grams of macroreticular strong acid ion-exchange resin and 57 grams ethanol were 0.4 - 1.7 % loaded in a 250 mL autoclave reactor. The autoclave was closed and heated to 125° C. A feed mixture consisting of 90 g furfuryl alcohol (43 mole percent), 55 g ethanol (56 mole percent) and 1.5 g (0.4 mole percent) of n-dodecane as internal standard was continuously fed to the autoclave under continuous stirring (1500 rpm). The temperature was maintained at 125° C. After addition of the whole feed mixture, the reactor was cooled and the liquid reaction mixture was analysed by gas chromatography. With Purolite MN500, Time= 0.883333 - 1.16667h, T= 125 °C , Conversion of starting material Patent; Van De Graaf, Wouter David; Lange, Jean-Paul; US2007/49771; (2007); (A1) English View in Reaxys

Rx-ID: 29540484 View in Reaxys 30/630 Yield 49.9 %Chromat., 10.2 %Chromat., 37.9 %Chromat.

Conditions & References 13.25 :Example 13The effect of the contacting time upon the catalytic activity was examined. The contacting time was controlled by varying the amount of the catalyst and the flow rate. The experimental conditions were the same as those of Example 8 but using the catalyst F as catalyst and flowing the mixed gas at a flow rate of 10 to 300 mL/ min. Here, the time in which the starting gas contacts the catalyst is defined to be,(Contacting time) [gcatalyst*sec/cc-starting gas]=(amount of catalyst) [g]/(flow rate)[mL/min].x.60 The results were as shown in Table 7. With Ni on C12-MCM-41, Time= 2h, T= 673 °C , p= 750.075Torr , Gas phase, Inert atmosphere Patent; Iwamoto, Masakazu; Yamamoto, Takashi; Haishi, Teruki; US2010/168491; (2010); (A1) English

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View in Reaxys

Rx-ID: 40975853 View in Reaxys 31/630 Yield

Conditions & References 2.3. Ethanol carbonylation flow reactor General procedure: Gas-phase reactions were carried out in quartz down flow microreactors in an Altamira Instruments BenchCAT 4000R-HP. Mixtures of ethanol and ethyl iodide co-catalyst were delivered via liquid syringe pump (KD Scientific KDS-100) at total liquid flow rates of 2-5 lL/min. The ethanol-to-ethyl iodide ratio was controlled in the range of 5-100:1. The liquid feed was vaporized in line with CO reactant. CO-to-ethanol molar ratios varied from 2 to 18:1, and CO flow rates were varied between 5 mL/min and 30 mL/min. The catalyst bed consisted of 0.1–1.5 g of catalyst held in place by quartz wool, and the reactions were conducted at reactor temperatures of 150–210 °C and nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. , Time= 5h, T= 170 °C , p= 760.051Torr , Flow reactor Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys 2.3. Ethanol carbonylation flow reactor General procedure: Gas-phase reactions were carried out in quartz down flow microreactors in an Altamira Instruments BenchCAT 4000R-HP. Mixtures of ethanol and ethyl iodide co-catalyst were delivered via liquid syringe pump (KD Scientific KDS-100) at total liquid flow rates of 2-5 lL/min. The ethanol-to-ethyl iodide ratio was controlled in the range of 5-100:1. The liquid feed was vaporized in line with CO reactant. CO-to-ethanol molar ratios varied from 2 to 18:1, and CO flow rates were varied between 5 mL/min and 30 mL/min. The catalyst bed consisted of 0.1–1.5 g of catalyst held in place by quartz wool, and the reactions were conducted at reactor temperatures of 150–210 °C and nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. , Time= 7h, T= 170 °C , p= 760.051Torr , Flow reactor Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys O

Rx-ID: 8871276 View in Reaxys 32/630 Yield

Conditions & References With polyoxomolybdate cluster, silica gel, T= 100 - 300 °C , Product distribution, Further Variations: Catalysts Bielanski, Adam; Malecka-Lubanska, Anna; Pozniczek, Joanna; Mueller, Achim; Krickemeyer, Erich; Diemann, Ekkehard; Bulletin of the Polish Academy of Sciences, Chemistry; vol. 49; nb. 1; (2001); p. 85 - 100 View in Reaxys With pyridine, Catalox® SCFa-140 gamma-alumina in water, T= 349.84 °C , Kinetics, Temperature DeWilde, Joseph F.; Czopinski, Christopher J.; Bhan, Aditya; ACS Catalysis; vol. 4; nb. 12; (2014); p. 4425 4433 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. With silica gel, T= 249.84 °C , p= 760.051Torr , Inert atmosphere

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Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys Catalytic experiments were performed at atmospheric pressurein a tubular flow reactor (i.d. 6 mm) using 0.5 g catalyst (60–70 meshsieved, thus with a ratio between the particle diameter and the internal reactor diameter near 25) and feeding 7.9percent (v/v) ethanolin nitrogen with 1.43 h−1 WHSV (total flow rate of 80 cm 3/min). The carrier gas (nitrogen) was passed through a bubbler containing ethanol (96percent) maintained at constant temperature (298 K) inorder to obtain the desired partial pressures. The temperature in the experiment was varied stepwise from 423 K to 773 K. With silica gel, T= 449.84 °C , p= 760.051Torr , Inert atmosphere Phung, Thanh Khoa; Hernndez, Loriana Proietti; Busca, Guido; Applied Catalysis A: General; vol. 489; nb. 1; (2015); p. 180 - 187 View in Reaxys

Fmoc-Lys(CH3)2-OH.HCl salt

NH 2 HO

Fmoc-Lys(CH3)2-PABA

Rx-ID: 33398307 View in Reaxys 33/630 Yield

Conditions & References 1 : For Fmoc-PheCit-OH 1e: For Fmoc-Lys(CH3)2-PABA 2i, Fmoc-Lys(CH3)2-OH.HCl salt (433 mg, 1 mmol) and PABA (246 mg, 2 mmol) were dissolved in DCM (10 mL) and MeOH (1.5 mL), cooled to 5° C. and EEDQ (495 mg, 2 mmol) was added. The cooling bath was removed and the mixture was stirred for 10 h at room temperature. All volatiles were removed on a rotovap, the residue was triturated with Et2O, and the crude product was filtered off. It was redissolved in a mixture of DCM (2 mL) and MeOH (1 mL) and precipitated again by adding dropwise into Et2O (40 mL). Product was filtered and dried in vacuo. Yield 448 mg (83percent). For Fmoc-Leu-PABA 2j, a solution of Fmoc-Leu-OH (353 mg, 1 mmol), EEDQ (495 mg, 2 mmol) and PABA (222 mg, 1.8 mmol) in DCM (10 mL) was stirred for 10 h. With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in methanol, 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran Patent; ARROWHEAD MADISON INC.; US2012/172412; (2012); (A1) English View in Reaxys I

Rx-ID: 35191462 View in Reaxys 34/630 Yield Ca. 55 %

Conditions & References With oxygen-covered Au nanoparticles on Au(111), T= -123.16 - -33.16 °C , p= 2E-10Torr Xu, Bingjun; Madix, Robert J.; Friend, Cynthia M.; Physical Chemistry Chemical Physics; vol. 15; nb. 9; (2013); p. 3179 - 3185 View in Reaxys

Cl H 2N

Rx-ID: 35494768 View in Reaxys 35/630 Yield

Conditions & References 14 : Preparation of a Biotin-Containing Labeling Reagent (M0789) Example 14 Preparation of a Biotin-Containing Labeling Reagent (M0789)

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To a solution of biotinylamidocaproic acid-N-hydroxysuccinimide ester (biotin-X-NHS; 100 mg, 0.22 mmol) and M0748 (43 mg, 0.23 mmol) in dry DMF (4 mL) was added diisopropylethylamine (80 μL, 0.46 μmol) and this reaction mixture allowed to stir at room temperature under dry N2(g) overnight. EtOAc (25 mL) was added to precipitate the product. The solids were isolated by centrifugation and washed with EtOAc (3*10 ml) and 1:9 MeOH:EtOAc (1*10 ml). The solids were dried in vacuo to give a white solid. (M0784: 70 mg, 65percent) homogeneous by TLC analysis (irrigant=15percent MeOH in CH2Cl2). A sample of M0784 (50 mg, 102 μmol) was dissolved in methanol (2 mL). Triisopropylsulfonyl hydrazide (32 mg, 107 μmol) was added and this reaction mixture allowed to stir at room temperature under dry N2(g) overnight. The solvent was removed in vacuo and the resulting solids were tritrated with diethyl ether (2*5 mL) followed by EtOAc (1*5 mL). With N-ethyl-N,N-diisopropylamine in methanol, ethyl acetate, N,N-dimethyl-formamide Patent; Naleway, John J.; Jiang, Ying; Link-Cole, Ryan; US2013/150254; (2013); (A1) English View in Reaxys

Rx-ID: 36351201 View in Reaxys 36/630 Yield

Conditions & References 111 : Example 111 Example 111 Synthesis of mPEG12K-b-Poly-(Asp(OH)10)-b-Poly-(d-Leu 20-co-Tyr(OH)20)-Ac mPEG12K-b-Poly-(Asp(Ot-Bu)10)-bPoly-(d-Leu20-co-Tyr(OBn)20)-Ac from Example 110 (314.5 g, 14.9 mmol) and pentamethylbenzene (141.4 g, 0.954 mole) were dissolved into 2.2 L of trifluoroacetic acid (TFA). The reaction was rapidly stirred for 14 hours at ambient room temperature. The TFA was removed on a rotary evaporator with the water bath temperature not exceeding 35 °C. The resultant putty-like solid was dissolved in 1.4 L of dichloromethane, transferred to a 12 L tub, and precipitated by slow addition of 5.6 L of diethyl ether using rapid mechanical stirring. The resultant slurry was stirred for 30 minutes, solids were collected by filtration, washed with 2x1L portions of fresh diethyl ether, and vacuum dried. The solid was redissolved in 900 mL of dichloromethane and precipitated by addition of 10 L of diethyl ether. Filtration and vacuum drying afforded the product as a colorless, fluffy solid (254.4 g, Yield = 91.3 percent). 1H NMR (d -DMSO) δ 12.4, 9.09, 8.50-7.80, 7.05-6.45, 4.65-4.0, 3.85-3.1, 3.03-2.45, 2.44-1.63, 1.58-0.95, 6 0.90-0.50. With trifluoroacetic acid in dichloromethane Patent; Intezyne Technologies Inc.; Sill, Kevin; Carie, Adam; Vojkovsky, Tomas; Semple, Edward J.; EP2660255; (2013); (A1) English View in Reaxys

O O

N Z O

Rx-ID: 30879128 View in Reaxys 37/630 Yield

Conditions & References O.94 : Preparation of Example 94 Compound 69 (2.58 g, 11.35 mmol) was dissolved in THF (35 mL). Boc2O (4.95 g, 22.7 mmol) was added to this solution, followed by DMAP (277 mg, 2.27 mmol). The reaction vessel was then placed in a 55° C. oil bath, which was then raised to 75° C., in order to achieve reflux. The reaction was cooled to rt after 3 h and then concentrated.

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The residue was dissolved in CH2Cl2 and this solution was extracted with 0.5N HCl (2*100 mL), brine and sat. NaHCO3(aq.). The organic phase was dried over MgSO4, and the drying agent was removed by vacuum filtration. The filtrate was concentrated and the residue was taken on to the next reaction. The residue from the above reaction was dissolved in THF (23 mL) and a solution of LiOH.H2O (952 mg, 22.7 mmol) in H2O (15 mL) was added by pipette at rt. The reaction was stirred overnight. The reaction was still not complete so additional LiOH.H2O (1.06 g) in H2O (10 mL) was added. After another 1.5 h the reaction was complete. The reaction placed in an ice bath and made brought to ~pH 2 with 2N HCl. The mixture was concentrated and then partitioned between CH2Cl2 and H2O. The layers were separated and the aqueous layer was back-extracted with CH2Cl2. The combined organics were dried over Na2SO4. The drying agent was removed by vacuum filtration and the product carboxylic acid was semi-purified by silica gel column chromatography. The semi-purified material was taken on to the next reaction. The product from the above reaction was dissolved in THF (100 mL). 2-tert-Butyl-1,3-diisopropyl-isourea (5 g, 25 mmol) was added to this solution and the reaction was placed in a 40° C. oil bath and stirred overnight. The next day additional 2-tert-Butyl-1,3-diisopropyl-isourea (6.8 g) was added and the bath temperature was increased to 55° C. After 2.5 h the reaction was cooled to it and then cooled to 0° C. The precipitated solids were removed by vacuum filtration and were washed with ice cold Et2O. The filtrate was concentrated and compound 70 (2.68 g, 72percent over 3 steps) was isolated from the residue by silica gel column chromatography as a clear, colorless oil. 1H NMR (400 MHz, D -DMSO): δ 7.06 (d, J=7.6 Hz, 1H), 6.73 (d, J=6 Hz, 1H), 5.78 (m, 1H), 4.99 (dd, J=16.8, 1.6 6 Hz, 1H), 4.93 (dt, J=10, 1 Hz, 1H), 3.74 (dd, J=13.6, 8.4 Hz, 1H), 2.00 (quart, J=7.2 Hz, 2H), 1.54 (m, 2H), 1.19-1.40 (m, 23H) With 4-(N,N-dimethlyamino)pyridine in tetrahydrofuran, hydrogenchloride, dichloromethane, water Patent; Gilead Sciences, Inc.; US2011/135599; (2011); (A1) English View in Reaxys

NH 2Cl O

NH 2

Rx-ID: 31758156 View in Reaxys 38/630 Yield

Conditions & References Synthetic Procedures Synthetic Procedures Aminoisobutyric acid methyl ester hydrochloride 2 Aminoisobutyric acid (29.80 g, 0.2890 mol) was suspended in MeOH (300 mL) and the suspension cooled to 0° C. (ice bath). Thionyl chloride (36.10 g, 0.3034 mol) was added dropwise over 15 min. The ice bath was removed and the reaction mixture stirred at 60° C. for 4 h. The oil bath was then removed and stirring continued at room temperature for another 22 h. The solvent and excess thionyl chloride were evaporated affording a white solid with a strong sulfur smell. Methanol (5*150 mL) was added and evaporated. The residue was dissolved in MeOH (120 mL), precipitated by addition of Et2O (720 mL) and collected by filtration under suction affording the title compound as a white solid (35.12 g, 79percent), with spectral characteristics in accordance with literature data'; 1H NMR (200 MHz, DMSO-d6) δ 8.87 (br s, 3H, NH3 +), 3.72 (s, 3H, OCH3), 1.48 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 172.0, 55.8, 53.1, 23.3; HRMS (m/z): M+ calcd. for C51H12NO2, 118.0868. found, 118.0871; Anal. Calcd. for C5H12ClNO2: C, 39.10; H, 7.87; N, 9.12. Found: C, 38.9; H, 7.8; N, 9.0. With thionyl chloride in methanol Patent; Universitetet i Oslo; US2011/263479; (2011); (A1) English View in Reaxys

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O HN

F O

N Br

N F

HN O

H 2N

F F

Rx-ID: 33397748 View in Reaxys 39/630 Yield

Conditions & References 66.l : l) l) 5-Bromo-pyridine-2-carboxylic acid [3-((3R*,6R*)-5-amino-3,6-dimethyl-6-tri-fluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amide hydrochloride ((2R*,5R*)-5-{3-[(5-bromo-pyridine-2-carbonyl)-amino]-phenyl}-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl)-carbamic acid tert-butyl ester (0.113 g, 0.194 mmol) was dissolved in THF (1 ml) and 4N HCl (5 ml) and the reaction mixture was stirred for 2 h at 25° C. and 3 h at 40° C. The solvents were removed under reduced pressure and the resulting residue was titurated with Et2O to provide the title compound as a white amorphous solid: TLC (EtOAc/MeOH 9:1): Rf=0.56; HPLC RtH5=1.147 min; 1H NMR (600 MHz, DMSO-d6): δ 11.45 (s, 1H), 10.81 (s, 1H), 9.74 (d, 2H), 8.88 (dd, 1H), 8.34 (dd, 1H), 8.10 (d, 1H), 8.01 (d, 1H), 7.95 (s, 1H), 7.46 (t, 1H), 7.27 (d, 1H), 4.13 (d, 1H), 4.05 (d, 1H), 1.81 (s, 3H), 1.69 (s, 3H); ESIMS: 471, 473 [(M+H) +]. With hydrogenchloride in tetrahydrofuran Patent; Novartis AG; US8338413; (2012); (B1) English View in Reaxys

Rx-ID: 37426325 View in Reaxys 40/630 Yield 16.3 %

Conditions & References With SiO2-MgO (wet-kneading, SiO2 particle size 30-100 nm), Time= 4h, T= 424.84 °C , Inert atmosphere, Catalytic behavior, Reagent/catalyst, Overall yield = 51.5 percent Angelici, Carlo; Velthoen, Marjolein E. Z.; Weckhuysen, Bert M.; Bruijnincx, Pieter C. A.; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2869 - 2879 View in Reaxys 2.2. Catalyst testing The catalytic tests were carried out at 325°C, at atmospheric pressure with a weight hourly space velocity (WHSV) of 0.3h−1. Argon was used as the carrier gas (8ml/min), the catalyst was packed into a quartz reactor and the catalytic reactions were carried out for 3–4h. The exhaust gases were analysed via GC-MS on an Agilent 7890A instrument with a HP-PLOT/Q, 30m long 0.530mm diameter column equipped with FID/MS detectors. The GC was calibrated as detailed elsewhere [6]. To determine the response factor (RF) for acetone the average of the RFs for diethyl ether and acetaldehyde were used. In all cases satisfactory carbon balances were obtained, typically better than 90percent. We observed no evidence for butanols, crotonaldehyde, ethyl-acetate or acetaldol products. Presumably, crotonaldehyde and acetaldol are formed in-situ but are too short lived to be detected. With 95:5 MgO:SiO2 impregnated ZrO2/ZnO, T= 325 °C , p= 760.051Torr , Inert atmosphere, Flow reactor, Gas phase, Catalytic behavior, Reagent/catalyst Lewandowski, Marek; Babu, Gowri S.; Vezzoli, Massimiliano; Jones, Matthew D.; Owen, Rhodri E.; Mattia, Davide; Plucinski, Pawel; Mikolajska, Ewelina; Ochenduszko, Agnieszka; Apperley, David C.; Catalysis Communications; vol. 49; (2014); p. 25 - 28 View in Reaxys

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With MgO-SiO2, T= 399.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor Janssens, Wout; Makshina, Ekaterina V.; Vanelderen, Pieter; De Clippel, Filip; Houthoofd, Kristof; Kerkhofs, Stef; Martens, Johan A.; Jacobs, Pierre A.; Sels, Bert F.; ChemSusChem; vol. 8; nb. 6; (2015); p. 994 - 1008 View in Reaxys

Rx-ID: 209139 View in Reaxys 41/630 Yield

Conditions & References With boron trifluoride, water, T= 200 °C , p= 36775.4Torr Patent; du Pont de Nemours &amp; Co.; US2135455; (1935) View in Reaxys With aluminum oxide, water, T= 100 °C Patent; Brown; Odell; US1907317; (1927) View in Reaxys With diboron trioxide, water, T= 340 °C , p= 18387.7Torr Patent; I.G.Farbenind.; GB408304 View in Reaxys Patent; I.G.Farbenind.; US2084390; (1933) View in Reaxys With pumice stone, water, calcium chloride, T= 300 °C , p= 18387.7Torr Patent; Dreyfus; US2126952; (1932) View in Reaxys Patent; Dreyfus; FR745084 View in Reaxys With sulfuric acid, Herstellung Fritzsche; Chem. Zentralbl.; vol. 83; nb. II; (1912); p. 1769 View in Reaxys With sodium alum, water, Herstellung Patent; Chem.Werke BYK; DE278777; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 12; p. 32 View in Reaxys With sulfuric acid, technische Darstellung durch Hydratisierung Himmler; ; vol. 5; (1954); p. 781 View in Reaxys Park; Beamer; ; vol. 5; (1950); p. 866 View in Reaxys

Rx-ID: 2899741 View in Reaxys 42/630 Yield

Conditions & References With aluminum oxide, rhenium, hydrogen, T= 230 °C , p= 22501.8Torr , kinetics and selectivity of reaction, influence of different catalysts Avaev, V. I.; Ryashentseva, M. A.; Minachev, Kh. M.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 37; nb. 1; (1988); p. 15 - 19; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; nb. 1; (1988); p. 22 - 27 View in Reaxys

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With hydrogen, rhenium, T= 190 °C , further temperature; influence of temperature and total pressure, Product distribution Minachev, Kh. M.; Avaeav, V. I.; Ryashentseva, M. A.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 35; nb. 2; (1986); p. 280 - 283; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; nb. 2; (1986); p. 306 - 310 View in Reaxys 3 : Example 3 Performance Tests General procedure: Example 3 Performance Tests [0123] The catalysts of Examples 1-2 and Comparative Examples A and B were fed to a test unit using one of the following running conditions. Reactor System and Catalytic Testing Conditions. [0124] The test unit comprised four independent tubular fixed bed reactor systems with common temperature control, pressure and gas and liquid feeds. The reactors were made of inch (0.95 cm) 316 SS tubing, and were 12 inches (30.8 cm) in length. The vaporizers were made of inch (0.95 cm) 316 SS tubing and were 12 inches (31.45 cm) in length. The reactors, vaporizers, and their respective effluent transfer lines were electrically heated (heat tape). [0125] The reactor effluents were routed to chilled water condensers and knock-out pots. Condensed liquids were collected automatically, and then manually drained from the knock-out pots as needed. Non-condensed gases were passed through a manual back pressure regulator (BPR) and then scrubbed through water and vented to the fume hood. For each Example, 15 ml of catalyst (3 mm pellets) was loaded into reactor. Both inlet and outlet of the reactor were filled with glass beads (3 mm) to form the fixed bed. Ethyl acetate was used as the feed. The following running conditions for catalyst screening were used: T=275° C., P=300 psig (2068 kPag), [Feed of EtOAc]=0.16 ml/min (pump rate), [H2]=513 L/min, [N2]=0.1 L/min, and gas-hourly space velocity (GHSV)=1473 hr−1. [0126] The crude product was analyzed by gas chromatograph (Agilent GC Model 6850), equipped with a flame ionization detector. The GC analytical results of the liquid product effluent, excluding water, are provided below in Table 8. The crude ethanol product for Comparative A contained over 3.9 wt. percent diethyl ether and Comparative B contained over 6.2 wt. percent diethyl ether. Thus, despite the higher conversions of ethyl acetate, more diethyl ether was produced. In contrast, the lower ether selectivities of Examples 1 and 2 resulted in low diethyl ether concentrations in the crude ethanol product. Example 2 contained less than 0.1 wt. percent diethyl ether and Example 1 contained no diethyl ether. With hydrogen, T= 275 °C , p= 16274.9Torr , Flow reactor Patent; CELANESE INTERNATIONAL CORPORATION; Wollrab, Radmila; Zhou, Zhenhua; Zink, James H.; Johnston, Victor J.; Weiner, Heiko; US2014/163263; (2014); (A1) English View in Reaxys O

O –O

OH Na +

Na +

O–

Rx-ID: 22835770 View in Reaxys 43/630 Yield 56.0g (100%)

Conditions & References 1 : Example 14-But-2-ynyloxy-benzenesulfonic acid sodium salt Example 1 4-But-2-ynyloxy-benzenesulfonic acid sodium salt To a solution of 52.35g (0.225 mol) of 4-hydroxybenzenesulfonate sodium salt in 1L of isopropanol and 225 ML of a 1.0N solution of sodium hydroxide was added 59.96g (0.45 mol) of 1-bromo-2-butyne.. The resulting mixture was heated to 70° for 15h and then the isopropanol was removed by evaporation in vacuo.. The resulting white precipitate was collected by filtration, washed with isopropanol and ether and dried in vacuo to give 56.0g (100percent) of the butynyl ether as a white solid. With sodium hydroxide in isopropyl alcohol Patent; American Cyanamid Company; EP1279674; (2003); (A2) english View in Reaxys

Rx-ID: 23399930 View in Reaxys 44/630 Yield

Conditions & References B :This experiment demonstrates the reaction of methanol with carbon monoxide in the presence of hydrogen, a rhodium catalyst, dppp and a ruthenium promoter during a 30 MIN RUN TIME. SYNGAS comprising hydrogen and car-

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bon at a H2 : CO mol ratio of 2: 1 was used (no C02 was present in the syngas). In this experiment the phosphinerhodium complex was generated in situ. 1. 114 gram of dppp was placed in a portion of the methanol charge (ca. 60g) with 0. 658 gram of (acac) Rh (CO) 2 to form a catalyst precursor suspension. 2.590 gram OF RUC13. 3H20 was placed in the autoclave together with approximately 5 gram of methanol and the autoclave was pressure tested. The MeI co-catalyst was added to the autoclave followed by the catalyst precursor suspension. The remaining methanol was added and the autoclave was pressurised with syngas (approximately 20 barg). The experiment was then conducted as for Comparative Example A. Reaction conditions are given in Table lb. Product distribution data is given in Table 2, product selectivity data is given in Table 3. The predominant liquid products are ethanol plus its precursor acetaldehyde. Acetic acid and its derivative MeOAc are formed in relatively small amounts With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], 1,3-bis-(diphenylphosphino)propane, methyl iodide, Time= 0.5h, T= 140 °C , p= 50255Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 12 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, 2,2'-bis((diphenylphosphino)methyl)-1,1'-biphenyl, [rhodium(I)(carbonyl)2(acetylacetonate)], methyl iodide, Time= 0.85h, T= 140 °C , p= 50105Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 8 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], BIPHEP, methyl iodide, Time= 2h, T= 140 °C , p= 50780.1Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 4 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], 9,9-dimethyl-4,5-bis[bis(2-methylphenyl)phosphanyl]xanthene, methyl iodide, Time= 1.33333h, T= 140 °C , p= 51005.1Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 10 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], 2,6-bis-(diphenylphosphino-methyl)pyridine, methyl iodide, Time= 2h, T= 140 °C , p= 50255Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 11 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, terpyridine, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], methyl iodide, Time= 1.71667h, T= 140 °C , p= 49429.9Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English

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View in Reaxys 13 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], dpp-eae, methyl iodide, Time= 0.55h, T= 140 °C , p= 50180Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 5 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], Nixantphos, methyl iodide, Time= 2h, T= 140 °C , p= 50255Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 9 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], TERPHOS, methyl iodide, Time= 2h, T= 140 °C , p= 51005.1Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 7 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], 1,1,4,7,7-pentaphenyl-1,4,7-triphosphaheptane, methyl iodide, Time= 2h, T= 140 °C , p= 51005.1Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 6 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], bis(1,2-diphenylphosphino)benzene, methyl iodide, Time= 2h, T= 140 °C , p= 50255Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys

N N

H 2N

N N

Rx-ID: 24142389 View in Reaxys 45/630 Yield

Conditions & References 104 : 1-[1-(3,4-Dichloro-phenyl)-1H-imidazol-4-yl-methyl]-1H-imidazol-2-yl-amine-, Hydrochloride (1:2) EXAMPLE 104 1-[1-(3,4-Dichloro-phenyl)-1H-imidazol-4-yl-methyl]-1H-imidazol-2-yl-amine-, Hydrochloride (1:2) 1H-Imidazole, 1-[[1-(3,4-dichlorophenyl)-1H-imidazol-4-yl]methyl]-2-nitro-(2.1 g, 6.2 mmol) was dissolved in acetic acid (50 ml), iron powder (3.5 g, 62 mmol) was added and the resulting mixture was stirred at 60° C. for 2h. After addition of AcOEt (200 ml), the hot mixture was again brought to reflux and filtered.

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All volatiles were removed in vacuo and residual acid was removed by co-evaporation with toluene. The semi-solid obtained was purified by chromatography [silica, elution with gradient CH2Cl2 to 100percent (CH2Cl2/ MeOH/aq. NH4OH=90:10:1)] and the free base of the title compound (1.9 g, 100percent) was isolated as an off-white solid. After treatment with a solution of HCl in MeOH followed by addition of Et2O the title compound was isolated as a white crystalline solid. Mp. 164-165° C. (MeOH/Et2O), MS: m/e=308(M+H+). Examples 105 to 107 were prepared according to the general procedure described in example 104. With hydrogenchloride in methanol, acetic acid, ethyl acetate, toluene Patent; Alanine, Alexander; Buettelmann, Bernd; Heitz Neidhart, Marie-Paule; Jaeschke, Georg; Pinard, Emmanuel; Wyler, Rene; US2002/151715; (2002); (A1) English View in Reaxys

FF F F

F F N+

(v5)F

(v5)

F F F

(v5)

F (v5)

F (v3)

F F

F (v5)F

F F

Pt–

(v6)

N+

(v6)

FF F F

F (v2) Pt–

(v6)

F F

(v2)

(v3) (v4)

F F

Rx-ID: 26415805 View in Reaxys 46/630 Yield

Conditions & References

85 %

With PPh3 in dichloromethane, Addn. to a CH2Cl2 soln. of Pt2Ag-compd. of an equimolar amt. of PPh3 and stirring of mixt. (exclusion of light, room temp., 2 h).; Evapn. of soln. to dryness and washing of resulting solid with n-hexane. Uson, Rafael; Fornies, Juan; Tomas, Milagros; Casas, Jose M.; Cotton, Albert F.; et al.; Organometallics; vol. 7; (1988); p. 2279 - 2285 ; (from Gmelin) View in Reaxys

Rx-ID: 28259676 View in Reaxys 47/630 Yield

Conditions & References 8; 9 :Examples 8-9; The processes were identical to Example 1, except that the feedstocks were ethanol aqueous solutions, containing 15percent and 50percent of ethanol, respectively, instead of ethanol (95percent). The target product was ethyl ether. The reaction results are shown in Table 7, wherein the weight ratios of the coked catalyst and the spent catalyst entering the regenerator for the coke-burning regeneration are about 0.02, 0.015, respectively. With CGP-1 (containing 25 wtpercent af REY zeolite, 10 wtpercent of ZSP-zeolite, and the balanced support) in water, T= 150 - 200 °C , p= 750.075Torr , Product distribution / selectivity Patent; China Petroleum and Chemical Corporation; Research Institute Of Petroleum Processing, Sinopec; EP2042476; (2009); (A1) English View in Reaxys

O OH

O O

Rx-ID: 10631501 View in Reaxys 48/630

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Yield

Conditions & References DIETHYL SUCCINATE EXAMPLE The reactive distillation experiment for esterification of succinic acid used a prereactor at 120°C to produce Feed 1 stream from the prereactor stream as shown in Figure 47. The prereactor feed constitutes a 10:1 molar ratio of ethanol to succinic acid. The stream Feed 1 represents an equilibrium mixture. In the reactive distillation column, the conversion of residual succinic acid (SA) from Feed 1 is about 45percent. Monoethyl succinate (MES) is also about 50percent converted in the RD column to produce additional diethyl succinate, the desired final product. The results of this Example shown in Table 9 illustrate the capability of reactive distillation to produce diethyl succinate from succinic acid. Table 9 Results of Succinic Acid Esterification via Reactive Distillation (All values are species flow rates in g/min) Species Prereactor Feed 1 Feed 2 Distillate Bottoms Succinic acid 4.1 0.2 0 0 0.119 Monoethyl succinate 1.03 0 0 0.514 Diethyl succinate 4.73 0 0 5.39 EtOH 15.9 12.66 15 19.42 8.05 Water 1.29 0 1.36 0 Diethyl ether 0.096 0 0.10 0 TOTAL 20.0 20.0 15.0 20.9 14.1 With Amberlyst 15, T= 120 °C Patent; Board of Trustees of Michigan State University; EP1849764; (2007); (A1) English View in Reaxys

Rx-ID: 29106950 View in Reaxys 49/630 Yield

Conditions & References With zeolite ZSM-5, T= 400 °C , p= 760.051Torr , Fixed bed reactor Mentzel, Uffe V.; Shunmugavel, Saravanamurugan; Hruby, Sarah L.; Christensen, Claus H.; Holm, Martin S.; Journal of the American Chemical Society; vol. 131; nb. 46; (2009); p. 17009 - 17013 View in Reaxys

Rx-ID: 37535145 View in Reaxys 50/630 Yield

Conditions & References 3,3'-dibromo-1,1'-biphenyl n-Butyllithium, 2.5M in hexane: 100mL (1.0 eq, 250 mmol) copper(II)chloride: 36,97 g (1.1 eq, 275 mmol) diethylether: 800 mL Yield: 22.06 g (56percent) GC-MS: m/z = 310 / 312 / 314 in hexane Patent; Novaled AG; Zöllner, Mike; Wutke, Jens; Bukhardt, Martin; EP2722908; (2014); (A1) English View in Reaxys 3,3'-dibromo-5,5'-dimethoxy-1,1'-biphenyl n-Butyllithium, 2.5M in hexane: 27mL (1.0 eq, 67.8 mmol) copper(II)chloride: 9.12 g (1.1 eq, 67.8 mmol) diethylether: 200 mL Yield: 9.7g (85percent) GC-MS: m/z = 370 / 372 / 374 in hexane Patent; Novaled AG; Zöllner, Mike; Wutke, Jens; Bukhardt, Martin; EP2722908; (2014); (A1) English View in Reaxys 3,3'-dibromo-5,5'-dimethyl-1,1'-biphenyl n-Butyllithium, 2.5M in hexane: 100mL (1.0 eq, 250 mmol)

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copper(II)chloride: 36,97 g (1.1 eq, 275 mmol) diethylether: 800 mL Yield: 22.1 g (52percent) GC-MS: m/z = 338 / 340 / 342 in hexane Patent; Novaled AG; Zöllner, Mike; Wutke, Jens; Bukhardt, Martin; EP2722908; (2014); (A1) English View in Reaxys

Rx-ID: 23251473 View in Reaxys 51/630 Yield

Conditions & References

0.4 %, < 0.05 %, 0.1 %, 10.8 %, 3.1 %, < 0.05 %

E : Comparative Example E This experiment demonstrates the reaction of methanol with carbon monoxide in the presence of hydrogen by a rhodium catalyst in the presence of dppp, but in the absence of a ruthenium promoter, during a 2 hour run time. A mixture of hydrogen and carbon at a H2 : CO ratio of 2: 1 was used. The reaction was performed according to the method of Comparative Example D using the charge composition and reaction conditions as detailed in Tables 3a and 3b respectively. Product distribution and product selectivity data is given in Tables 4 and 5 respectively. With carbon monoxide, 1,3-bis-(diphenylphosphino)propane, hydrogen, (acac)Rh(CO)2, methyl iodide, Time= 2h, T= 140 °C , p= 52505.3Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101488; (2004); (A1) English View in Reaxys

Rx-ID: 40651641 View in Reaxys 52/630 Yield

Conditions & References

48.9 %

With Cu(1.0 wtpercent)Hf(3.0 wtpercent)-silica supported catalyst, Time= 3.5h, T= 300 - 360 °C , Reagent/catalyst De Baerdemaeker, Trees; Feyen, Mathias; Müller, Ulrich; Yilmaz, Bilge; Xiao, Feng-Shou; Zhang, Weiping; Yokoi, Toshiyuki; Bao, Xinhe; Gies, Hermann; De Vos, Dirk E.; ACS Catalysis; vol. 5; nb. 6; (2015); p. 3393 3397 View in Reaxys

I O

Rx-ID: 630620 View in Reaxys 53/630 Yield 16 %

Conditions & References With carbon monoxide, hydrogen, dirhodium tetraacetate, diethylphosphinoethane, Time= 4h, T= 120 °C , p= 30400Torr Simpson, Michael C.; Payne, Marc J.; Cole-Hamilton, David J.; Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999); nb. 19; (1994); p. 2899 - 2900 View in Reaxys T= 200 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 411 View in Reaxys With sodium acetylamide Titherley; Journal of the Chemical Society; vol. 79; (1901); p. 398 View in Reaxys

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Time= 0.00138889h, examination of ethylation by using a dual-cell Fourier transform mass spectrometer;, Product distribution Bjarnason, Asgeir; Organic Mass Spectrometry; vol. 24; (1989); p. 847 - 848 View in Reaxys in gas, in the source of a mass spectrometer; primary and secondary isotopic effect investigated by labeled compounds, Mechanism Audier, H. E.; Monteiro, C.; Robin, D.; Organic Mass Spectrometry; vol. 24; (1989); p. 146 View in Reaxys OH

SO2

Rx-ID: 7086555 View in Reaxys 54/630 Yield

Conditions & References With sulfuric acid, T= 140 °C , Darstellung Evans; Sutton; Journal of the American Chemical Society; vol. 35; (1913); p. 794 View in Reaxys

Rx-ID: 23399931 View in Reaxys 55/630 Yield

Conditions & References A :This experiment demonstrates the reaction of methanol with carbon monoxide in the presence of hydrogen, a rhodium catalyst, dppp AND A ruthenium promoter during a 2 hour run time. Dppp is a bidentate phosphine ligand. Syngas comprising hydrogen and carbon at a H2 : CO mol ratio of 2: 1 was used (no C02 was present in the syngas). 2.031 gram of (dppp) Rh (COMe) I2 and 2.115 gram OF RUC13 were suspended in a portion of the methanol charge and charged to the autoclave. The reactor was then pressure tested with nitrogen, vented via a gas sampling system, and flushed with synthesis gas three times. The remaining liquid components of the reaction composition (the remaining methanol and methyl iodide) were charged to the autoclave via a liquid addition port. The autoclave was then pressurised with 5 barg of syngas and slowly vented. The autoclave was then pressurised with synthesis gas (approximately 20 barg) and heated with stirring (1220 r. p. m. ) to reaction temperature, 140°C. Once stable at temperature (about 15 minutes), the total pressure was raised to the desired operating pressure by feeding syngas from the ballast vessel. The reactor pressure was maintained at a constant value (I 0. 5 barg) by feeding gas from the ballast vessel throughout the experiment. Gas uptake from the ballast vessel was measured using datalogging facilities throughout the course of the experiment. The reaction temperature was maintained within 1 °C of the desired reaction temperature by means of a heating mantle connected to a Eurotherm (Trade Mark) control system. After a suitable time, T, (see Table LB), the ballast vessel was isolated and the reactor rapidly cooled by use of the cooling coils. Product distribution data is given in Table 2, product selectivity data is given in Table 3. THE predominating liquid products are ethanol and its derivatives (EtOMe and ET20) plus its precursor acetaldehyde. Acetic acid and its derivative MeOAc are formed in relatively small amounts With hydrogen, ruthenium trichloride, cis-Rh{Ph2P(CH2)3PPh2}(COCH3)(I)2, methyl iodide, Time= 2h, T= 140 °C , p= 50255Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys C :This experiment demonstrates the reaction of methanol with carbon monoxide in the presence of hydrogen, a rhodium catalyst, dppp, but in the absence of a ruthenium promoter, during a 2 hour run time. Syngas comprising hydrogen and carbon at a H2 : CO mol ratio of 2: 1 was used (no C02 was present in the syngas). The reaction was perfonned according to the method of Comparative Example B using a charge composition and reaction conditions as shown in Tables la and lb below. Product distribution data is given in Table 2. Product selectivity data is given in Table 3. In the absence of ruthenium the main liquid product is acetaldehyde. Acetic acid and its derivative MeOAc are also formed

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With hydrogen, [rhodium(I)(carbonyl)2(acetylacetonate)], 1,3-bis-(diphenylphosphino)propane, methyl iodide, Time= 2h, T= 140 °C , p= 52505.3Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys 3 :Examples 3 to 11 were conducted according to the method of Comparative Example B using charge compositions and reaction conditions as shown in Tables la and lb. Product distribution data is given is Table 2. Product selectivity data is given in Table 3 With hydrogen, ruthenium trichloride, [rhodium(I)(carbonyl)2(acetylacetonate)], 2,2'-bis-(diphenylphosphino)-1,1'- binaphthyl, methyl iodide, Time= 0.75h, T= 140 °C , p= 51680.2Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2004/101487; (2004); (A1) English View in Reaxys

N HO

S N H

O S

O O

Rx-ID: 23993759 View in Reaxys 56/630 Yield

Conditions & References 95 : Example 95 Example 95 To a mixture of 300 mg of 4-tert.-butyl-N-[6-chloro-5-(p-tolyl)-4-pyrimidinyl]-benzene sulfonamide (Example 12c) and 1.8 g of 4-methoxy-2-butyn-1-ol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) was added 288 mg of 55percent NaH in mineral oil. After evolution of gas had ceased, the brown suspension was stirred at room temperature for 24 h. Another 288 mg of 55percent NaH in mineral oil was added and the mixture was stirred at 60° C. for 18 h. The mixture was cooled, diluted with 50 ml of 10percent aqueous citric acid and extracted 4 times with 50 ml of ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluding with hexane:ethyl acetate 1:1 and precipitated from diethyl ether to give 213 mg of 4-tert.-butyl-N-[6-(4-methoxy-2-butynyloxy)-5-(p-tolyl)-4-pyrimidinyl]benzene sulfonamide as a white powder. LC-MS: tR=5.61 min, [M+1]+=480.30, [M-1]-=478.39. With NaH in mineral oil Patent; Bolli, Martin; Boss, Christoph; Clozel, Martine; Fischli, Walter; US2003/87920; (2003); (A1) English View in Reaxys

F BH–4 Na +

B F

F O

B– F Na + F

(v2) (v2) (v2) (v2)H H(v6) BH H(v6) (v6)H BH (v6) HB (v6) BH (v6) (v6) HB BH (v6)

(v6)

B BB H H H (v6)

Rx-ID: 26449433 View in Reaxys 57/630

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Yield

Conditions & References

47 %

With potassium permanganate, sulfuric acid in water, diethylene glycol, benzene, byproducts: H2; NaBH4 in diglyme heated to 105°C and BF3*OEt2 added for 6 h and stirred for 1 h, mixt. cooled under N2 atm., water added, diglyme removed, H2SO4, benzene and KMnO4 added and react. mixt. stirred at 10°C; mixt. filtered, layers separated, benzene layer washed with water and dried over anhyd. MgSO4, evapd. and sublimed Dunks, Gary B.; Barker, Kathryn; Hedaya, Eddie; Hefner, Catherine; Palmer-Ordonez, Kathy; Remec, Peter; Inorganic Chemistry; vol. 20; (1981); p. 1692 - 1697 ; (from Gmelin) View in Reaxys

44 %

With sulfuric acid, dihydrogen peroxide, iron(II) sulfate in hexane, water, diethylene glycol, byproducts: H2; NaBH4 in diglyme heated to 105°C and BF3*OEt2 added for 6 h and stirred for 1 h, mixt. cooled under N2 atm., water added, diglyme removed, H2SO4, hexane and FeSO4, then H2O2 added and react. mixt. stirred at 35°C; mixt. filtered, layers separated, hexane layer washed with water and dried over anhyd. MgSO4 Dunks, Gary B.; Barker, Kathryn; Hedaya, Eddie; Hefner, Catherine; Palmer-Ordonez, Kathy; Remec, Peter; Inorganic Chemistry; vol. 20; (1981); p. 1692 - 1697 ; (from Gmelin) View in Reaxys

41.1 %

With sulfuric acid, dihydrogen peroxide in water, diethylene glycol, benzene, byproducts: H2; NaBH4 in diglyme heated to 105°C and BF3*OEt2 added for 6 h and stirred for 1 h, mixt. cooled under N2 atm., water added, diglyme removed, H2SO4, benzene and then H2O2 added and react. mixt. stirred for 68 h; mixt. filtered, layers separated, benzene layer washed with water and dried over anhyd. MgSO4 Dunks, Gary B.; Barker, Kathryn; Hedaya, Eddie; Hefner, Catherine; Palmer-Ordonez, Kathy; Remec, Peter; Inorganic Chemistry; vol. 20; (1981); p. 1692 - 1697 ; (from Gmelin) View in Reaxys

40.2 %

With potassium dichromate, sulfuric acid in water, diethylene glycol, benzene, byproducts: H2; NaBH4 in diglyme heated to 105°C and BF3*OEt2 added for 6 h and stirred for 1 h, mixt. cooled under N2 atm., water added, diglyme removed, H2SO4, benzene and K2Cr2O7 added and react. mixt. stirred at 30°C; mixt. filtered, layers separated, benzene layer washed with water and dried over anhyd. MgSO4 Dunks, Gary B.; Barker, Kathryn; Hedaya, Eddie; Hefner, Catherine; Palmer-Ordonez, Kathy; Remec, Peter; Inorganic Chemistry; vol. 20; (1981); p. 1692 - 1697 ; (from Gmelin) View in Reaxys With sulfuric acid, dihydrogen peroxide, iron(II) sulfate in hexane, water, byproducts: H2; NaBH4 in diethylcarbitol heated to 105°C and BF3*OEt2 added for 6 h and stirred for 1 h, mixt. cooled under N2 atm., water added, diethylcarbitol removed, H2SO4, hexane and FeSO4, then H2O2 added and react. mixt. stirred at 35°C; mixt. filtered, layers separated, hexane layer washed with water and dried over anhyd. MgSO4 Dunks, Gary B.; Barker, Kathryn; Hedaya, Eddie; Hefner, Catherine; Palmer-Ordonez, Kathy; Remec, Peter; Inorganic Chemistry; vol. 20; (1981); p. 1692 - 1697 ; (from Gmelin) View in Reaxys With sulfuric acid, dihydrogen peroxide, iron(II) sulfate in hexane, water, diethylene glycol, byproducts: H2; NaBH4 in diglyme heated to 105°C and BF3*OEt2 added for 6 h and stirred for 1 h, mixt. cooled under N2 atm., water added, diglyme removed, soln. allowed to stand overnight, crystals dissolved in water, H2SO4,hexane, FeSO4 and then H2O2 added; mixt. filtered, layers separated, hexane layer washed with water and dried over anhyd. MgSO4 Dunks, Gary B.; Barker, Kathryn; Hedaya, Eddie; Hefner, Catherine; Palmer-Ordonez, Kathy; Remec, Peter; Inorganic Chemistry; vol. 20; (1981); p. 1692 - 1697 ; (from Gmelin) View in Reaxys

O N

Rx-ID: 36671460 View in Reaxys 58/630

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Yield

Conditions & References 2.2 : Complex with Substituted Phenylphenanthridine Example 2.2 Complex with Substituted Phenylphenanthridine A mixture of 6-[4-(2-{2-[2-(2-Methoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-phenyl]-phenanthridine (1 g, 2.16 mmol), IrCl3.3H2O (346 mg, 0.98 mmol) in 16 ml of 2-EtOEtOH:H2O (12:4) was refluxed overnight under nitrogen atmosphere. The reaction mixture was cooled down to room temperature and 60 ml of water were added to obtain an oily precipitate. The supernatant was discarded and 50 ml of water were added to the residue. The mixture was stirred for 1 h to obtain a red-brownish precipitate. The solid was filtrated and washed with water (50 ml) and Et2O (30 ml). The brown solid was dissolved in the smaller amount of dichloromethane and precipitated upon addition of Et2O. It was used in the next step without further purification. in dichloromethane, water Patent; Bergmann, Frank; Cysewski, Robert; de Cola, Luisa; Dziadek, Sebastian; Fernandez Hernandez, Jesus Miguel; Josel, Hans-Peter; Seidel, Christoph; US2015/140682; (2015); (A1) English View in Reaxys

NH 2

Rx-ID: 39321823 View in Reaxys 59/630 Yield

Conditions & References 1 : Synthesis of Fmoc Dipeptides 1a-h. For Fmoc-Lys(CH3)2-PABA 2i, Fmoc-Lys(CH3)2-OH*HCl salt (433 mg, 1 mmol) and PABA (246 mg, 2 mmol) were dissolved in DCM (10 ml) and MeOH (1.5 ml), cooled to 5° C. and EEDQ (495 mg, 2 mmol) was added. The cooling bath was removed and the mixture was stirred for 10 h at RT (room temperature). All volatiles were removed on a rotovap, the residue was triturated with Et2O, and the crude product was filtered off. It was redissolved in a mixture of DCM (2 ml) and MeOH (1 ml) and precipitated again by adding dropwise into Et2O (40 ml). Product was filtered and dried in vacuo. Yield 448 mg (83percent). For Fmoc-Leu-PABA 2j, a solution of Fmoc-Leu-OH (353 mg, 1 mmol), EEDQ (495 mg, 2 mmol) and PABA (222 mg, 1.8 mmol) in DCM (10 ml) was stirred for 10 h. With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline Patent; Cheng, Weijun; Wong, So; Almeida, Aaron M.; Rozema, David B.; Blokhin, Andrei V.; Carlson, Jeffrey C.; US2015/45573; (2015); (A1) English View in Reaxys OH

Rx-ID: 209140 View in Reaxys 60/630 Yield

Conditions & References With sulfuric acid, T= 150 °C , p= 36775.4Torr Patent; Distillers Co.; US1960633; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 21; p. 81 View in Reaxys Patent; Distillers Co.; DE596819; (1931) View in Reaxys With sulfuric acid, T= 200 °C , p= 147102 - 294203Torr , auch in Gegenwart von ZnCl2 Patent; Universal Oil Prod.Co.; US2179092; (1932) View in Reaxys With sulfuric acid, water, T= 170 °C , p= 5884.06Torr

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Patent; Air Reduction Co.; US2050442; (1934) View in Reaxys O

O O

Rx-ID: 249086 View in Reaxys 61/630 Yield

Conditions & References With ammonia, sodium amide, toluene, T= 110 °C , und anschliessendem Kochen mit Diaethylsulfat in Toluol Cope; Hancock; Journal of the American Chemical Society; vol. 60; (1938); p. 2904,2905 View in Reaxys

Rx-ID: 3341972 View in Reaxys 62/630 Yield

Conditions & References With hydrogen, immobilized colloidal rhodium particle in ethanol, water, T= 30 °C , p= 760Torr , several olefines investigated; catalytic activity also investigated Hirai, Hidefumi; Ohtaki, Michitaka; Komiyama, Makoto; Chemistry Letters; (1987); p. 149 - 152 View in Reaxys With hydrogen, immobilized colloidal rhodium particles in ethanol, water, T= 30 °C , p= 760Torr Hirai, Hidefumi; Ohtaki, Michitaka; Komiyama, Makoto; Chemistry Letters; (1987); p. 149 - 152 View in Reaxys With ammonia-borane, C17H45N5Si3Zr, T= 65 °C , Inert atmosphere Erickson, Karla A.; Stelmach, John P. W.; Mucha, Neil T.; Waterman, Rory; Organometallics; vol. 34; nb. 19; (2015); p. 4693 - 4699 View in Reaxys

HO HO

OH OH

Rx-ID: 23310898 View in Reaxys 63/630 Yield 28.5 %, 57.5 %

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fuel alcohol comprises a metal atom-containing catalyst, a promoter and optionally ligands, solvents and/or secondary activators. A variety of references disclose the synthesis of fuel alcohol from syngas. See, for example, (i) El Sawy, A. H., DOE report DE90010325 and references therein, the entireties of which are incorporated herein by reference; (ii) Courty, Charmette, Raimbault and Travers, Rev. De Institute du Petrole, vol. 45(4), 561-578 (1990), the entireties of which are incorporated herein by reference; and (iii) Klier, Herman, Simmons and Lyman, DOE report DE89009888 and references therein, the entireties of which are incorporated herein by reference. Fuel alcohol synthesis may occur at a variety of reaction conditions. In one embodiment, the fuel alcohol synthesis reaction temperature in the fuel alcohol synthesis zone ranges from about 200° C. to about 500° C., preferably from about 250° C. to about 450° C., and most preferably from about 300° C. to about 400° C. The pressure in the fuel alcohol synthesis zone also may vary widely, although the pressure preferably is in the range of the pressure of the syngas that is directed to the methanol synthesis unit, discussed above. Optionally, the pressure in the fuel alcohol synthesis zone ranges from about 5 to about 20 MPa, preferably from about 6 to about 18 MPa, and most preferably from about 10 to about 15 MPa. Although many different fuel alcohol synthesis catalysts may be utilized in the fuel alcohol synthesis zone to facilitate conversion of the syngas contained therein to fuel alcohol, the fuel alcohol synthesis catalyst preferably comprises a microporous zeolitic material. Thus, in one embodiment, the fuel alcohol is formed by contacting syngas with a fuel alcohol synthesis catalyst comprising a microporous zeolitic material under conditions effective to convert the syngas to fuel alcohol, which is contained in a fuel alcohol-containing stream. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises copper and an oxide of zinc. Additionally, in this embodiment, the fuel alcohol synthesis catalyst preferably comprises an oxide of one or both of chromium and/or aluminum. Specifically, in this embodiment, the fuel alcohol synthesis catalyst preferably comprises one or more of Cu/ZnO/ Cr2O3 and Cu/ZnO/Al2O3. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali promoted. Thus, the fuel alcohol optionally is formed in this aspect of the invention by contacting syngas with a fuel alcohol synthesis catalyst comprising one or more of Cu/ZnO/Cr2O3 and Cu/ZnO/Al2O3, which fuel alcohol synthesis catalyst optionally is alkali promoted, under conditions effective to convert the syngas to the fuel alcohol. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises an oxide of one or more of zinc, chromium, copper, cobalt, and nickel. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali, lanthanum or cerium promoted. Thus, the fuel alcohol optionally is formed in this aspect of the invention by contacting syngas with a fuel alcohol synthesis catalyst under conditions effective to convert the syngas to the fuel alcohol, wherein the fuel alcohol synthesis catalyst comprises an oxide of one or more of zinc, chromium, copper, cobalt, and nickel, which fuel alcohol synthesis catalyst optionally is alkali, lanthanum or cerium promoted. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises a compound comprising molybdenum and preferably sulfur. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali promoted. Specifically, the fuel alcohol optionally is catalyzed by one or more of MoS2 and Co/MoS2. Thus, the fuel alcohol can be formed by contacting syngas with a fuel alcohol synthesis catalyst under conditions effective to convert the syngas to the fuel alcohol, wherein the fuel alcohol synthesis catalyst comprises one or more of MoS2 and Co/MoS2, and wherein the fuel alcohol synthesis catalyst optionally is alkali promoted. The alkali metal atom component of the catalyst system can come from any of the known ionic compounds of the alkali metals sodium, potassium, lithium, rubidium and cesium. Preferred alkali metal atom components are derived from sodium salts and potassium salts. Illustrative sources thereof include sodium iodide, sodium bicarbonate, sodium carbonate, sodium nitrate, sodium nitrite, sodium sulfate, sodium bisulfate, sodium chromate, sodium permanganate, sodium chlorate, sodium persulfate, sodium tetraborate, sodium bromide, sodium chloride, sodium fluoride, sodium sulfite, sodium hypochlorite, as well as any other ionic salt of sodium. Rather than repeat the individual compound names, the corresponding potassium, lithium, rubidium and cesium salts are illustrative of useful ionic compounds. The concentration of alkali metal atoms in the fuel alcohol synthesis zone optionally is from about 0.00013 to about 1 mole per liter; preferably from about 0.07 to about 0.6 mole per liter. Preferably, hydrogen and carbon monoxide are present in the syngas that is directed to the fuel alcohol synthesis zone. The molar ratio of H2:CO in the syngas that is directed to the fuel alcohol synthesis zone can vary from about 20:1 to about 1:20, from about 10:1 to about 1:10, and preferably from about 3:1 to about 1:3. Particularly in continuous operations, but also in batch experiments, the carbon monoxide-hydrogen gaseous mixture may also be used in conjunction with up to 50percent by volume of one or more other gases. These other gases may include one or more inert gases such as nitrogen, argon, neon and the like, or they may include gases that may, or may not, undergo reaction under CO hydrogenation conditions, such as carbon dioxide, hydrocarbons such as methane, ethane, propane and the like, ethers such as dimethyl ether, methylethyl ether and diethyl ether, alkanols such as methanol and acid esters such as methyl acetate. According to the present invention, a fuel alcohol-containing stream is formed, which comprises the fuel alcohol. The fuel alcohol-containing stream preferably comprises two or more alcohols in the C2 to C5 range. Higher alcohols and carboxylic acid esters may also be formed while carrying out the process of this invention. For example, the fuel alcohol-containing stream may include methyl formate, methyl acetate, ethyl acetate, ethyl ether. The major by-products of the process such as the higher molecular weight alcohols and carboxylic acid esters, are, of course, also useful compounds and major articles of commerce. The higher alcohols, the carboxylic acid esters and ethers can easily be separated from one another by conventional means, e.g., fractional distillation in vacuo, if desired. The precise amount and type of components contained in the fuel alcohol-containing stream will vary widely depending on catalyst type, reaction conditions, and syngas composition used. For example,

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Table I, below, provides three catalyst systems and indicates exemplary product yields and operating conditions. See El Sawy, A. H., DOE report DE90010325, pp. 3-17, 3-18. Product Yields (Wt. percent) and Reaction Conditions of Three Fuel Alcohol Synthesis Systems Process Product Slate Main Catalyst Constituents (anhydrous basis) Cu/Co/Al Zn/Cr/K Cu/ZnO/Al Methanol 57.5 70.0 64.5 Ethanol 28.5 2.5 11.5 C3 alcohols 7.1 3.4 5.2 C4 alcohols 2.8 12.5 7.4 C5+ alcohols 2.5 9.5 7.4 Hydrocarbons 0.3 - 0.02 Esters 0.7 0.1 0.8 Other Oxygenated 0.6 2.0 3.18 Products Total Alcohols 98.4 97.9 96.0 Operating T (° C.) 260-320 350-420 285-300 Operating Pressure 6-10 10-18 6-9 (MPa) Syngas Feed Ratio 2.0-2.5 1.5-2 0.5-1 (H2:CO)Syngas CO2 0.5-3.0 2-6 1.0 Content (Vol. percent) As indicated by Table I, the amount of ethanol contained in the fuel alcohol-containing stream may vary. The fuel alcohol-containing stream preferably comprises at least about 10 weight percent ethanol, more preferably at least about 25 weight percent ethanol and most preferably at least about 35 weight percent ethanol, based on the total weight of the fuel alcohol-containing stream. In terms of ranges, the fuel alcohol-containing stream optionally comprises on the order of from about 5 to about 60 weight percent ethanol, preferably from about 10 to about 50 weight percent ethanol, and most preferably from about 20 to about 40 weight percent ethanol, based on the total weight of the fuel alcoholcontaining stream. The fuel alcohol-containing stream also comprises one or more C3 alcohols, preferably on the order of from about 5 to about 80 weight percent C3 alcohols, preferably from about 10 to about 60 weight percent C3 alcohols, and most preferably from about 15 to about 40 weight percent C3 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C3 alcohols comprise one or more of 1-propanol, 2-propanol, and/or 1,2-propadiol. Additionally or alternatively, the fuel alcohol-containing stream comprises one or more C4 alcohols, preferably on the order of from about 0.1 to about 20 weight percent C4 alcohols, preferably from about I to about 10 weight percent C4 alcohols, and most preferably from about 2 to about 5 weight percent C4 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C4 alcohols comprise one or more of I -butanol; 2-butanol; 1,4-butanediol; 1,3-butanediol; 1,2-butanediol; isobutyl alcohol; sec-butyl alcohol; and t-butyl alcohol. The fuel alcohol-containing stream preferably comprises at least about 5 weight percent C3-C4 alcohols, more preferably at least about 10 weight percent C3-C4 alcohols, and most preferably at least about 15 weight percent C3-C4 alcohols. Optionally, the fuel alcohol-containing stream comprises one or more C5 alcohols, preferably on the order of from about 0.01 to about 10 weight percent C5 alcohols, preferably from about 0.1 to about 5 weight percent C5 alcohols, and most preferably from about 0.1 to about 3 weight percent C5 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C5 alcohols comprise one or more of 1-pentanol; 2-pentanol; 3pentanol; 1,5-pentanediol; 1,4-pentanediol; 1,3-pentanediol; and 1,2-pentanediol. Additionally, the fuel alcohol-containing stream optionally comprises one or more C6+ alcohols, preferably on the order of from about 0.01 to about 10 weight percent C6+ alcohols, preferably from about 0.1 to about 5 weight percent C6+ alcohols, and most preferably from about 0.1 to about 3 weight percent C6+ alcohols, based on the total weight of the fuel alcohol-containing stream. Ideally, the fuel alcohol-containing stream contains low amounts of methanol, if any. Preferably, the fuel alcohol-containing stream comprises less than 75 weight percent methanol, more preferably less than 65 weight percent methanol, and most preferably less than 60 weight percent methanol, based on the total weight of the fuel alcohol-containing stream. In terms of weight ratios, if the fuel alcohol-containing stream comprises methanol and ethanol, then the weight ratio of methanol to ethanol ranges from about 1 to about 6, more preferably from about 1.5 to about 5, and most preferably from about 2 to about 4. If the fuel alcohol-containing stream comprises ethanol and C3 alcohols, then the weight ratio of ethanol to C3 alcohols preferably ranges from about 1 to about 30, more preferably from about 5 to about 30, and most preferably from about 10 to about 20. The novel process of this invention can be conducted in a batch, semi-continuous or continuous fashion. The catalyst may be initially introduced into the fuel alcohol synthesis zone batchwise, or it may be continuously or intermittently introduced into such a zone during the course of the synthesis reaction. Operating conditions can be adjusted to optimize the formation of the fuel alcohol product, and after recovery of the alcohol and other products, a fraction rich in the catalyst composition may then be recycled to the reaction zone, if desired, and additional products generated. A non-limiting list of preferred reactor types for the synthesis of fuel alcohol includes fixed bed, slurry reactors and fluid bed reactors. One can additionally have an inert solvent present in the reaction mixture. A wide variety of substantially inert solvents are useful in the process of this invention including hydrocarbon and oxygenated hydrocarbon solvents. Suitable oxygenated hydrocarbon solvents are compounds comprising carbon, hydrogen and oxygen and those in which the only oxygen atoms present are in ether groups, ester groups, ketone carbonyl groups or hydroxyl groups of alcohols. Generally, the oxygenated hydrocarbon will contain 3 to 12 carbon atoms and preferably a maximum of 3 oxygen atoms. The solvent preferably is substantially inert under reaction conditions, is relatively non-polar and has a normal boiling point of at least 65° C. at atmospheric pressure, and preferably, the solvent will have a boiling point greater than that of ethanol and other oxygen-containing reaction products so that recovery of the solvent by distillation is facilitated. Preferred ester type solvents are the aliphatic and acylic carboxylic acid monoesters as exemplified by butyl acetate, methyl benzoate, isopropyl iso-butyrate, and propyl propionate as well as dimethyl adipate. Useful alcohol-type solvents include monohydric alcohols such as cyclohexanol, 1-hexanol, 2-hexanol, neopentanol, 2-octanol, etc. Suitable ketone-type solvents include, for example, cyclic ketones such as cyclohexanone, 2-methylcyclohexanone, as well as acylic ketones such as 2-pentanone, butanone, acetophenone, etc. Ethers that may be utilized as solvents include cyclic, acyclic and heterocyclic materials. Preferred ethers are the heterocyclic ethers as illustrated by 1,4-dioxane and 1,3-dioxane. Other suitable ether solvents include isopropyl propyl ether, diethylene glycol dibutyl ether, dibutyl

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ether, ethyl butyl ether, diphenyl ether, heptyl phenyl ether, anisole, tetrahydrofuran, etc. The most useful solvents of all of the above groups include the ethers as represented by monocyclic, heterocyclic ethers such a 1,4-dioxane or p-dioxane, etc. Hydrocarbon solvents, such as hexane, heptane, decane, dodecane, tetradecane, etc. are also suitable solvents for use in this invention. In the practice of this invention, it is also possible to add a small amount of water to the solvent and still obtain satisfactory results. The reaction time varies depending upon the reaction parameters, reactor size and charge, and the individual components employed at the specific process conditions. With hydrogen, Cu/Co/Al, T= 260 - 320 °C , p= 45004.5 - 75007.5Torr , Conversion of starting material Patent; Janssen, Marcel Johannes; Van Egmond, Cornelis F.; Martens, Luc R.M.; Sher, Jaimes; US2005/107481; (2005); (A1) English View in Reaxys 28.5 %, 57.5 %

C :As indicated above, the present invention, in one embodiment, provides for a combined process for forming methanol and fuel alcohol and converting the methanol and fuel alcohol to light olefins in an OTO reaction system. A nonlimiting description of several fuel alcohol synthesis systems that may be incorporated into the present invention will now be described. As with methanol synthesis, there are numerous technologies available for producing fuel alcohol. The preferred embodiment for forming fuel alcohol according to the present invention comprises the reaction of carbon monoxide, hydrogen and optionally carbon dioxide in the presence of a fuel alcohol synthesis catalyst to form fuel alcohol and water. The synthesis of fuel alcohol occurs in a fuel alcohol synthesis zone. Without limiting the invention to a particular reaction mechanism, the synthesis of fuel alcohol may be illustrated as follows: nCO+2nH2->CnH2n+1OH+(n-1)H2O (7) where n is a whole number. According to the present invention, the fuel alcohol synthesis reaction or reactions optionally are catalyzed using a fuel alcohol synthesis catalyst, preferably containing a metal atom, optionally with a halogen promoter. Many metal compounds and promoters can be used. Optionally, secondary activators or ligands may be used in conjunction with the metal catalysts and promoters. These secondary activators can be other metallic salts or compounds, amines, phosphorus compounds, as well as a multitude of other compounds that have been disclosed in the published literature. Thus, a typical catalyst system for the synthesis of fuel alcohol comprises a metal atom-containing catalyst, a promoter and optionally ligands, solvents and/or secondary activators. A variety of references disclose the synthesis of fuel alcohol from syngas. See, for example, (i) El Sawy, A. H., DOE report DE90010325 and references therein, the entireties of which are incorporated herein by reference; (ii) Courty, Charmette, Raimbault and Travers, Rev. De Institute du Petrole, vol. 45(4), 561-578 (1990), the entireties of which are incorporated herein by reference; and (iii) Klier, Herman, Simmons and Lyman, DOE report DE89009888 and references therein, the entireties of which are incorporated herein by reference. Fuel alcohol synthesis may occur at a variety of reaction conditions. In one embodiment, the fuel alcohol synthesis reaction temperature in the fuel alcohol synthesis zone ranges from about 200° C. to about 500° C., preferably from about 250° C. to about 450° C., and most preferably from about 300° C. to about 400° C. The pressure in the fuel alcohol synthesis zone also may vary widely, although the pressure preferably is in the range of the pressure of the syngas that is directed to the methanol synthesis unit, discussed above. Optionally, the pressure in the fuel alcohol synthesis zone ranges from about 5 to about 20 MPa, preferably from about 6 to about 18 MPa, and most preferably from about 10 to about 15 MPa. Although many different fuel alcohol synthesis catalysts may be utilized in the fuel alcohol synthesis zone to facilitate conversion of the syngas contained therein to fuel alcohol, the fuel alcohol synthesis catalyst preferably comprises a microporous zeolitic material. Thus, in one embodiment, the fuel alcohol is formed by contacting syngas with a fuel alcohol synthesis catalyst comprising a microporous zeolitic material under conditions effective to convert the syngas to fuel alcohol, which is contained in a fuel alcohol-containing stream. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises copper and an oxide of zinc. Additionally, in this embodiment, the fuel alcohol synthesis catalyst preferably comprises an oxide of one or both of chromium and/or aluminum. Specifically, in this embodiment, the fuel alcohol synthesis catalyst preferably comprises one or more of Cu/ZnO/ Cr2O3 and Cu/ZnO/Al2O3. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali promoted. Thus, the fuel alcohol optionally is formed in this aspect of the invention by contacting syngas with a fuel alcohol synthesis catalyst comprising one or more of Cu/ZnO/Cr2O3 and Cu/ZnO/Al2O3, which fuel alcohol synthesis catalyst optionally is alkali promoted, under conditions effective to convert the syngas to the fuel alcohol. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises an oxide of one or more of zinc, chromium, copper, cobalt, and nickel. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali, lanthanum or cerium promoted. Thus, the fuel alcohol optionally is formed in this aspect of the invention by contacting syngas with a fuel alcohol synthesis catalyst under conditions effective to convert the syngas to the fuel alcohol, wherein the fuel alcohol synthesis catalyst comprises an oxide of one or more of zinc, chromium, copper, cobalt, and nickel, which fuel alcohol synthesis catalyst optionally is alkali, lanthanum or cerium promoted. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises a compound comprising molybdenum and preferably sulfur. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali promoted. Specifically, the fuel alcohol optionally is catalyzed by one or more of MoS2 and Co/MoS2. Thus, the fuel alcohol can be formed by contacting syngas with a fuel alcohol synthesis catalyst under conditions effective to convert the syngas to the fuel alcohol, wherein the fuel alco-

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hol synthesis catalyst comprises one or more of MoS2 and Co/MoS2, and wherein the fuel alcohol synthesis catalyst optionally is alkali promoted. The alkali metal atom component of the catalyst system can come from any of the known ionic compounds of the alkali metals sodium, potassium, lithium, rubidium and cesium. Preferred alkali metal atom components are derived from sodium salts and potassium salts. Illustrative sources thereof include sodium iodide, sodium bicarbonate, sodium carbonate, sodium nitrate, sodium nitrite, sodium sulfate, sodium bisulfate, sodium chromate, sodium permanganate, sodium chlorate, sodium persulfate, sodium tetraborate, sodium bromide, sodium chloride, sodium fluoride, sodium sulfite, sodium hypochlorite, as well as any other ionic salt of sodium. Rather than repeat the individual compound names, the corresponding potassium, lithium, rubidium and cesium salts are illustrative of useful ionic compounds. The concentration of alkali metal atoms in the fuel alcohol synthesis zone optionally is from about 0.00013 to about 1 mole per liter; preferably from about 0.07 to about 0.6 mole per liter. Preferably, hydrogen and carbon monoxide are present in the syngas that is directed to the fuel alcohol synthesis zone. The molar ratio of H2:CO in the syngas that is directed to the fuel alcohol synthesis zone can vary from about 20:1 to about 1:20, from about 10:1 to about 1:10, and preferably from about 3:1 to about 1:3. Particularly in continuous operations, but also in batch experiments, the carbon monoxide-hydrogen gaseous mixture may also be used in conjunction with up to 50percent by volume of one or more other gases. These other gases may include one or more inert gases such as nitrogen, argon, neon and the like, or they may include gases that may, or may not, undergo reaction under CO hydrogenation conditions, such as carbon dioxide, hydrocarbons such as methane, ethane, propane and the like, ethers such as dimethyl ether, methylethyl ether and diethyl ether, alkanols such as methanol and acid esters such as methyl acetate. According to the present invention, a fuel alcohol-containing stream is formed, which comprises the fuel alcohol. The fuel alcohol-containing stream preferably comprises two or more alcohols in the C2 to C5 range. Higher alcohols and carboxylic acid esters may also be formed while carrying out the process of this invention. For example, the fuel alcohol-containing stream may include methyl formate, methyl acetate, ethyl acetate, ethyl ether. The major by-products of the process such as the higher molecular weight alcohols and carboxylic acid esters, are, of course, also useful compounds and major articles of commerce. The higher alcohols, the carboxylic acid esters and ethers can easily be separated from one another by conventional means, e.g., fractional distillation in vacuo, if desired. The precise amount and type of components contained in the fuel alcohol-containing stream will vary widely depending on catalyst type, reaction conditions, and syngas composition used. For example, Table I, below, provides three catalyst systems and indicates exemplary product yields and operating conditions. See El Sawy, A. H., DOE report DE90010325, pp. 3-17, 3-18. Product Yields (Wt. percent) and Reaction Conditions of Three Fuel Alcohol Synthesis Systems Process Product Slate Main Catalyst Constituents (anhydrous basis) Cu/Co/Al Zn/Cr/K Cu/ZnO/Al Methanol 57.5 70.0 64.5 Ethanol 28.5 2.5 11.5 C3 alcohols 7.1 3.4 5.2 C4 alcohols 2.8 12.5 7.4 C5+ alcohols 2.5 9.5 7.4 Hydrocarbons 0.3 - 0.02 Esters 0.7 0.1 0.8 Other Oxygenated 0.6 2.0 3.18 Products Total Alcohols 98.4 97.9 96.0 Operating T (° C.) 260-320 350-420 285-300 Operating Pressure 6-10 10-18 6-9 (MPa) Syngas Feed Ratio 2.0-2.5 1.5-2 0.5-1 (H2:CO)Syngas CO2 0.5-3.0 2-6 1.0 Content (Vol. percent) As indicated by Table I, the amount of ethanol contained in the fuel alcohol-containing stream may vary. The fuel alcohol-containing stream preferably comprises at least about 10 weight percent ethanol, more preferably at least about 25 weight percent ethanol and most preferably at least about 35 weight percent ethanol, based on the total weight of the fuel alcohol-containing stream. In terms of ranges, the fuel alcohol-containing stream optionally comprises on the order of from about 5 to about 60 weight percent ethanol, preferably from about 10 to about 50 weight percent ethanol, and most preferably from about 20 to about 40 weight percent ethanol, based on the total weight of the fuel alcoholcontaining stream. The fuel alcohol-containing stream also comprises one or more C3 alcohols, preferably on the order of from about 5 to about 80 weight percent C3 alcohols, preferably from about 10 to about 60 weight percent C3 alcohols, and most preferably from about 15 to about 40 weight percent C3 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C3 alcohols comprise one or more of 1-propanol, 2-propanol, and/or 1,2-propadiol. Additionally or alternatively, the fuel alcohol-containing stream comprises one or more C4 alcohols, preferably on the order of from about 0.1 to about 20 weight percent C4 alcohols, preferably from about I to about 10 weight percent C4 alcohols, and most preferably from about 2 to about 5 weight percent C4 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C4 alcohols comprise one or more of I -butanol; 2-butanol; 1,4-butanediol; 1,3-butanediol; 1,2-butanediol; isobutyl alcohol; sec-butyl alcohol; and t-butyl alcohol. The fuel alcohol-containing stream preferably comprises at least about 5 weight percent C3-C4 alcohols, more preferably at least about 10 weight percent C3-C4 alcohols, and most preferably at least about 15 weight percent C3-C4 alcohols. Optionally, the fuel alcohol-containing stream comprises one or more C5 alcohols, preferably on the order of from about 0.01 to about 10 weight percent C5 alcohols, preferably from about 0.1 to about 5 weight percent C5 alcohols, and most preferably from about 0.1 to about 3 weight percent C5 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C5 alcohols comprise one or more of 1-pentanol; 2-pentanol; 3pentanol; 1,5-pentanediol; 1,4-pentanediol; 1,3-pentanediol; and 1,2-pentanediol. Additionally, the fuel alcohol-containing stream optionally comprises one or more C6+ alcohols, preferably on the order of from about 0.01 to about 10 weight percent C6+ alcohols, preferably from about 0.1 to about 5 weight percent C6+ alcohols, and most preferably from about 0.1 to about 3 weight percent C6+ alcohols, based on the total weight of the fuel alcohol-containing stream. Ideally, the fuel alcohol-containing stream contains low amounts of methanol, if any. Preferably, the fuel alcohol-containing stream comprises less than 75 weight percent methanol, more preferably less than 65 weight per-

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cent methanol, and most preferably less than 60 weight percent methanol, based on the total weight of the fuel alcohol-containing stream. In terms of weight ratios, if the fuel alcohol-containing stream comprises methanol and ethanol, then the weight ratio of methanol to ethanol ranges from about 1 to about 6, more preferably from about 1.5 to about 5, and most preferably from about 2 to about 4. If the fuel alcohol-containing stream comprises ethanol and C3 alcohols, then the weight ratio of ethanol to C3 alcohols preferably ranges from about 1 to about 30, more preferably from about 5 to about 30, and most preferably from about 10 to about 20. The novel process of this invention can be conducted in a batch, semi-continuous or continuous fashion. The catalyst may be initially introduced into the fuel alcohol synthesis zone batchwise, or it may be continuously or intermittently introduced into such a zone during the course of the synthesis reaction. Operating conditions can be adjusted to optimize the formation of the fuel alcohol product, and after recovery of the alcohol and other products, a fraction rich in the catalyst composition may then be recycled to the reaction zone, if desired, and additional products generated. A non-limiting list of preferred reactor types for the synthesis of fuel alcohol includes fixed bed, slurry reactors and fluid bed reactors. One can additionally have an inert solvent present in the reaction mixture. A wide variety of substantially inert solvents are useful in the process of this invention including hydrocarbon and oxygenated hydrocarbon solvents. Suitable oxygenated hydrocarbon solvents are compounds comprising carbon, hydrogen and oxygen and those in which the only oxygen atoms present are in ether groups, ester groups, ketone carbonyl groups or hydroxyl groups of alcohols. Generally, the oxygenated hydrocarbon will contain 3 to 12 carbon atoms and preferably a maximum of 3 oxygen atoms. The solvent preferably is substantially inert under reaction conditions, is relatively non-polar and has a normal boiling point of at least 65° C. at atmospheric pressure, and preferably, the solvent will have a boiling point greater than that of ethanol and other oxygen-containing reaction products so that recovery of the solvent by distillation is facilitated. Preferred ester type solvents are the aliphatic and acylic carboxylic acid monoesters as exemplified by butyl acetate, methyl benzoate, isopropyl iso-butyrate, and propyl propionate as well as dimethyl adipate. Useful alcohol-type solvents include monohydric alcohols such as cyclohexanol, 1-hexanol, 2-hexanol, neopentanol, 2-octanol, etc. Suitable ketone-type solvents include, for example, cyclic ketones such as cyclohexanone, 2-methylcyclohexanone, as well as acylic ketones such as 2-pentanone, butanone, acetophenone, etc. Ethers that may be utilized as solvents include cyclic, acyclic and heterocyclic materials. Preferred ethers are the heterocyclic ethers as illustrated by 1,4-dioxane and 1,3-dioxane. Other suitable ether solvents include isopropyl propyl ether, diethylene glycol dibutyl ether, dibutyl ether, ethyl butyl ether, diphenyl ether, heptyl phenyl ether, anisole, tetrahydrofuran, etc. The most useful solvents of all of the above groups include the ethers as represented by monocyclic, heterocyclic ethers such a 1,4-dioxane or p-dioxane, etc. Hydrocarbon solvents, such as hexane, heptane, decane, dodecane, tetradecane, etc. are also suitable solvents for use in this invention. In the practice of this invention, it is also possible to add a small amount of water to the solvent and still obtain satisfactory results. The reaction time varies depending upon the reaction parameters, reactor size and charge, and the individual components employed at the specific process conditions. With hydrogen, Cu/ZnO/Al2O3, T= 285 - 300 °C , p= 45004.5 - 67506.8Torr , Conversion of starting material Patent; Janssen, Marcel Johannes; Van Egmond, Cornelis F.; Martens, Luc R.M.; Sher, Jaimes; US2005/107481; (2005); (A1) English View in Reaxys N

Rx-ID: 24649116 View in Reaxys 64/630 Yield

Conditions & References R.1 : Preparation of 2-mercaptopyrazine REFERENCE EXAMPLE 1 Preparation of 2-mercaptopyrazine 5.0 g of 2-chloropyrazine was dissolved in 40 ml of dimethylformamide and 5.0 g of NaSH.xH2 O was added thereto. The mixture was heated to 60° C. for 2 hours and cooled to 5° C. The resulting precipitates were filtered and 400 ml of diethylether was added to the filtrate. The precipitates were washed with diethylether and dried to give 3.0 g of yellow solid. IR(KBr): 1650, 1570, 1562, 1425cm-1 NMR(DMSO-d6) ppm: 7.60(d, 1H), 7.80(d, 1H), 8.55(s, 1H), 14.35(bs, 1H) in N-methyl-acetamide Patent; Kim; Nak Doo; US5658913; (1997); (A1) English View in Reaxys

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H2 C Ti

(v2)

C H2

O–

Ti2+

Rx-ID: 27086729 View in Reaxys 65/630 Yield

Conditions & References

86 %

With benzophenone in toluene, argon atmosphere or vac.; benzophenone addn. to Ti-complex soln.; solvent removal after 5 h, residue vac.-drying (20°C, 1E-3 mm Hg); elem. anal. Razuvaev, G. A.; Vyshinskaya, L. I.; Vasil'eva, G. A.; Malysheva, A. V.; Rabinovich, A. M.; Journal of General Chemistry USSR (English Translation); vol. 52; (1982); p. 1178 - 1184; Zhurnal Obshchei Khimii; vol. 52; (1982); p. 1338 - 1345 ; (from Gmelin) View in Reaxys OH

Rx-ID: 28121870 View in Reaxys 66/630 Yield

Conditions & References 4 :A reactor system was set up as described in Example 3 above. Etherification was performed using the reactor system with ethanol as a feedstock, instead of methanol.The reaction conditions for this example are summarized below in Table 3. Notably, the reaction was tested at three different ethanol flow rates, 11.64 g/min, 7.00 g/min, and 3.52 g/min. TABLE 3 Reactor Reactor Inlet Temp. Outlet Temp. EtOH Gases Burning Inlet Outlet of heater of heater Front Back Flow collection 1 L gas Temp. Temp. exchange exchanger Pressure Pressure Rate Rate time (° C.) (° C.) (° C.) (° C.) (PSI) (PSI) (g/min) (L/min) (seconds) 344 346 357 109 2500 2500 3.522 0.076 132 345 344 362 111 2500 2500 7.000 0.101 189 344 346 356 109 2500 2500 11.64 No Gases The resulting gas was shown to be combustible by igniting the same and observing it to burn. The mass balance (liquid in versus liquid out) of chemical reactions is shown below in Table 4. TABLE 4 EtOH EtOH EtOH Flow Flow Conversion EtOH to (g/min) at (g/min) Rate EtOH Gases Inlet at Outlet (g/min) Recovery Conversion 3.522 3.360 0.162 95.4percent 4.6percent 7.000 6.824 0.176 97.5percent 2.5percent 11.64 11.62 0.020 99.8percent 0.2percent A sample of gas from the reactor was collected in a gas tight cell for NIR (Near Infra-Red) analysis. The NIR spectrum for gas created with an ethanol flow rate of 3.52 g/min is shown in FIG. 6. This was compared with a standard curve NIR spectrum for pure ethane.A sample of liquid from the reactor was collected and subjected to NMR (proton nuclear magnetic resonance) analysis. The NMR spectrum for liquid created with an ethanol flow rate of 3.52 g/min is shown in FIG. 7. This was compared with an NMR spectrum for pure diethyl ether.NIR and NMR results indicated that at a flow rate of 7.00 g/min, the composition of the gas is diethyl ether, methane, and carbon monoxide. The NIR and NMR results further show that at a flow rate of 3.52 g/min, the composition of the gas is diethyl ether, methane, and carbon monoxide. The NIR and NMR results further show that at a flow rate of 11.64 g/min, little gas is produced.The data show that an alcohol feedstock including ethanol can be converted into an ether reaction product using a metal oxide catalyst. With Titanium(IV) oxide, T= 344 - 346 °C , p= 129290Torr , Gas phase, Conversion of starting material Patent; McNeff, Clayton V.; McNeff, Larry C.; Yan, Bingwen; US2008/319236; (2008); (A1) English View in Reaxys

NH 2 N

H 2N

N NH

N Cl

NH 2

HN S

H 2N

3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [8-(1-phenyl-ethyl)-1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide Rx-ID: 30618538 View in Reaxys 67/630

Yield

Conditions & References 246 : 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [8-(1-phenyl-ethyl)-1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide

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Example 246 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [8-(1-phenyl-ethyl)-1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide A mixture of 1-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-2-methyl-isothiourea (Intermediate A) (1.7 g, 4.54 mmol) and 4-aminomethyl-1-(1-phenyl-ethyl)-piperidin-4-ylamine (Intermediate BM) (1.6 g, 4.59 mmol) in propan-2-ol (50 ml) is stirred at 80° C. for 16 hours. The reaction mixture is concentrated in vacuo and purified by column chromatography (basic alumina, 0-2percent MeOH in DCM) to obtain pale yellow solid. The compound obtained is further dissolved in MeOH and precipitated by adding diethyl ether. The supernatant solvent mixture is decanted and the product is washed again with diethyl ether and dried under vacuum to afford the title compound as off-white solid; [M+H]+ 429. in methanol, 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran, isopropyl alcohol Patent; Vertex Pharmaceuticals Incorported; US2011/98311; (2011); (A1) English View in Reaxys O

Rx-ID: 30814241 View in Reaxys 68/630 Yield

Conditions & References

93 %, 5 %

With NaX faujasite, Time= 6h, T= 180 - 240 °C Selva, Maurizio; Fabris, Massimo; Perosa, Alvise; Green Chemistry; vol. 13; nb. 4; (2011); p. 863 - 872 View in Reaxys

Rx-ID: 36236069 View in Reaxys 69/630 Yield

Conditions & References Catalytic tests The experiments were performed in a 20-mL continuous fixed-bed reactor (PID Eng & Tech) fed by a HPLC pump (Gilson 307). The reactor bed consisted of resin homogeneously diluted with inert quartz. Quartz was used to keep the bed isothermal and to ensure good contact between reactants and catalyst. Back-mixing and channelling effects were avoided by using a resin to inert mass ratio large enough accordingly to previous studies in our lab. During the experiment liquid samples were taken on-line from the reactor inlet and outlet. Their composition was determined in an HP6890A GLC equipped with TCD detector. A 50 m × 0.2 mm × 0.5 μm capillary column HP-Pona (Agilent) was used to separate and quantify the compounds present in the reaction medium. The column was temperature programmed to start at 50 °C with a 25 °C/min ramp up to 250 °C and held for 6 min. Helium (≥99.998percent, Linde) was the carrier gas. Chemical species were identified by a second GLC apparatus equipped with mass spectrometer GC/MS 5973 (Agilent) assisted by a chemical database software. Catalysts were dried overnight at 110 °C under vacuum (0.01 bar). Dry samples (0.1–0.7 g) were diluted in quartz (12–15 g). Reactor feed consisted of an OcOH– EtOH mixture (ROcOH/EtOH = 10). The large excess of 1-octanol was selected to enhance the formation of EOE and DNOE in front of DEE, and also to promote the formation of 1-octenes, and in this way, to study the possible catalyst deactivation by carbon deposition. Water (1 wtpercent) was added to the reactant mixture in some runs to stress its effect on the reaction rate without the liquid splitting off in two phases. The feed was preheated in a hot box at 80 °C and then fed to reactor at a flow rate of 0.25 mL/min. The reactor operated isothermally at 25 bars in the temperature range 150–190 °C to assure that the reaction took place in the liquid phase. With quartz, Time= 70h, T= 150 °C , p= 18751.9Torr , Flow reactor, Catalytic behavior, Kinetics, Reagent/catalyst, Temperature Guilera, Jordi; Ramirez, Eliana; Fite, Carles; Iborra, Montserrat; Tejero, Javier; Applied Catalysis A: General; vol. 467; (2013); p. 301 - 309 View in Reaxys

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2 Na +

N Z

S–

–

Rx-ID: 38954522 View in Reaxys 70/630 Yield

Conditions & References EXEMPLIFICATION Ru Complex 6b Under an atmosphere of dry N2, a suspension of Ru complex 1 (100 mg, 0.160 mmol, 1.00 equiv) and sodium maleonitriledithiolate 4 (38.7 mg, 0.208 mmol, 1.30 equiv) is allowed to stir in tetrahydrofuran (1.5 mL) for 3 hours, during which a color change from green to reddish brown is observed. The solvent is evaporated and the residual tetrahydrofuran is removed through co-evaporation with pentane. The residue is taken up in dichloromethane and the solution filtered through a glass microfiber filter (Whatman™). After removal of the solvent in vacuo, dichloromethane (1.0 mL) is added and the complex precipitated while stirring by slow addition of diethyl ether (10 mL). The resulting suspension is transferred onto a short column of Celite (4 cm in height) placed in a pipette (˜0.5 cm diameter) and washed with a 1:10 mixture of dichloromethane/diethyl ether (5.5 mL). The first filtrate is collected and left for crystallization (see below). The complex is then eluted with dichloromethane until the second filtrate is colorless. After removal of the solvent and co-evaporation of dichloromethane with pentane, complex 6b is obtained as an orange-brown solid (75.0 mg, 0.109 mmol, 68percent yield). After two days, the crystals from the first filtrate were collected and washed with diethyl ether to give an overall yield of 6b of 82percent (90.0 mg, 0.131 mmol). 1H NMR (500 MHz, CD Cl ): δ 14.28 (1H, s), 7.34 (1H, td, J=7.8, 1.6 Hz), 7.16 (1H, d, J=8.4 Hz), 7.0-6.4 (1H, very br 2 2 s), 6.97 (2H, s), 6.85 (1H, t, J=7.4 Hz), 6.60 (1H, dd, J=7.6, 1.6 Hz), 6.4-5.9 (1H, br s), 5.38 (1H, m), 3.95 (4H, apparent br s), 2.5-1.9 (3H, very br s), 2.45 (6H, s), 2.25 (6H, br s), 1.9-1.4 (3H, very br s), 1.78 (3H, d, J=6.7 Hz), 1.49 (3H, d, J=6.6 Hz). in tetrahydrofuran, dichloromethane Patent; Hoveyda, Amir H.; Khan, R. Kashif M.; Torker, Sebastian; Koh, Ming Joo; US2014/371454; (2014); (A1) English View in Reaxys O O

H N

Rx-ID: 40794981 View in Reaxys 71/630 Yield

Conditions & References 2,7-Dimethoxy-9H-carbazole (11h) The crude biphenyl 10h (6.0 g) was dissolved in P(OEt)3 (36 mL). The vial was flushed with argon. The reaction mixture was heated to 90° C., kept at this temperature overnight, and cooled. As a result the carbazole precipitated. Et2O/CH2Cl2 mixture was added. The precipitate was filtered off and washed with CH2Cl2. With biphenyl Patent; Incuron, LLC; Tucker, John; Sviridov, Sergey; Brodsky, Leonid; Burkhart, Catherine; Purmal, Andrei; Gurova, Katerina; Gudkov, Andrei; US9108916; (2015); (B2) English View in Reaxys OH

I O

Rx-ID: 40975851 View in Reaxys 72/630 Yield

Conditions & References 2.3. Ethanol carbonylation flow reactor

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General procedure: Gas-phase reactions were carried out in quartz down flow microreactors in an Altamira Instruments BenchCAT 4000R-HP. Mixtures of ethanol and ethyl iodide co-catalyst were delivered via liquid syringe pump (KD Scientific KDS-100) at total liquid flow rates of 2-5 lL/min. The ethanol-to-ethyl iodide ratio was controlled in the range of 5-100:1. The liquid feed was vaporized in line with CO reactant. CO-to-ethanol molar ratios varied from 2 to 18:1, and CO flow rates were varied between 5 mL/min and 30 mL/min. The catalyst bed consisted of 0.1–1.5 g of catalyst held in place by quartz wool, and the reactions were conducted at reactor temperatures of 150–210 °C and nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. With carbon monoxide, O40PW12 (3-)*2.8Cs(1+)*0.2H(1+), Time= 5h, T= 170 °C , p= 760.051Torr , Flow reactor, Catalytic behavior, Reagent/catalyst Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys 2.3. Ethanol carbonylation flow reactor General procedure: Gas-phase reactions were carried out in quartz down flow microreactors in an Altamira Instruments BenchCAT 4000R-HP. Mixtures of ethanol and ethyl iodide co-catalyst were delivered via liquid syringe pump (KD Scientific KDS-100) at total liquid flow rates of 2-5 lL/min. The ethanol-to-ethyl iodide ratio was controlled in the range of 5-100:1. The liquid feed was vaporized in line with CO reactant. CO-to-ethanol molar ratios varied from 2 to 18:1, and CO flow rates were varied between 5 mL/min and 30 mL/min. The catalyst bed consisted of 0.1–1.5 g of catalyst held in place by quartz wool, and the reactions were conducted at reactor temperatures of 150–210 °C and nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. With carbon monoxide, Time= 5h, T= 170 °C , p= 760.051Torr , Flow reactor, Catalytic behavior, Reagent/catalyst Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys O O

S N

NH O

O O

N Cl

Rx-ID: 42171462 View in Reaxys 73/630 Yield 39 %

Conditions & References 30.2 : Step-2: Step-2: N-(2-chloropyrimidin-4-yl)-N-(tetrahydro-2H-pyran-3-yl)methanesulfonamide To a solution of N-(tetrahydro-2H-pyran-3-yl)methanesulfonamide (1.63 g, 9.09 mmol) in dimethylformamide (50 mL) cooled in an ice-water bath was added 60percent NaH in oil (0.55 g, 13.7 mmol) portionwise under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 15 minutes and then cooled in an ice-water bath. 2,4-Dichloropyrimidine (1.69 g, 11.3 mmol) was then added in one portion. The reaction mixture was allowed to warm up to room temperature and was stirred for 3 days. After removal of N,N-dimethylformamide under reduced pressure, the residue was partitioned between EtOAc and saturated NH4Cl aqueous solution. The organic layer was separated, washed with NaHCO3 (aqueous) and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography on an ISCO® chromatography system (80 g silica gel column, eluted with EtOAc/hexanes 0-100percent) to afford the title compound 2 as an off-white solid (1.04 g, 39percent yield). m.p. 107-109° C. 1H NMR (300 MHz, CDCl3): δ ppm 8.50 (d, J=5.7 Hz, 1H), 7.30 (d, J=5.5 Hz, 1H), 4.41 (m, 1H), 4.0 (m, 2H), 3.9 (m, 1H), 3.3 (m, 1H), 3.23 (s, 3H), 2.28 (m, 1H), 2.02 (m, 1H), 1.74-1.86 (m, 2H). LCMS (method 3): >96percent pure 254 nm, Rt 4.62 min, m/z 292, 294 [M+H]+.

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Patent; Forma Therapeutics, Inc.; Lin, Jian; Ericsson, Anna; Campbell, Ann-Marie; Gustafson, Gary; Wang, Zhongguo; Diebold, R Bruce; Ashwell, Susan; Lancia, JR., David R.; Caravella, Justin Andrew; Lu, Wei; (171 pag.); US2016/83365; (2016); (A1) English View in Reaxys I O

Rx-ID: 632113 View in Reaxys 74/630 Yield

Conditions & References With potassium carbonate Williamson; Justus Liebigs Annalen der Chemie; vol. 81; (1852); p. 77 View in Reaxys Williamson; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 40; (1854); p. 98; Justus Liebigs Annalen der Chemie; vol. 77; (1851); p. 38 View in Reaxys With sodium ethanolate Williamson; Justus Liebigs Annalen der Chemie; vol. 81; (1852); p. 77 View in Reaxys Williamson; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 40; (1854); p. 98; Justus Liebigs Annalen der Chemie; vol. 77; (1851); p. 38 View in Reaxys With Na2O, T= 180 °C Greene; Bulletin de la Societe Chimique de France; vol. &lt;2&gt; 29; (1878); p. 458 View in Reaxys With silver(l) oxide Wurtz; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 46; (1856); p. 222 View in Reaxys With mercury(II) oxide, schon bei laengerer Bestrahlung mit Sonnenlicht Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 411 View in Reaxys With water Frankland; Justus Liebigs Annalen der Chemie; vol. 71; (1849); p. 203; Justus Liebigs Annalen der Chemie; vol. 85; (1853); p. 360 View in Reaxys Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 411 View in Reaxys Nef; Justus Liebigs Annalen der Chemie; vol. 298; (1897); p. 322; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 50 View in Reaxys

OH OH

Rx-ID: 23310899 View in Reaxys 75/630

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Yield 28.5 %, 57.5 %

Conditions & References C :As indicated above, the present invention, in one embodiment, provides for a combined process for forming methanol and fuel alcohol and converting the methanol and fuel alcohol to light olefins in an OTO reaction system. A nonlimiting description of several fuel alcohol synthesis systems that may be incorporated into the present invention will now be described. As with methanol synthesis, there are numerous technologies available for producing fuel alcohol. The preferred embodiment for forming fuel alcohol according to the present invention comprises the reaction of carbon monoxide, hydrogen and optionally carbon dioxide in the presence of a fuel alcohol synthesis catalyst to form fuel alcohol and water. The synthesis of fuel alcohol occurs in a fuel alcohol synthesis zone. Without limiting the invention to a particular reaction mechanism, the synthesis of fuel alcohol may be illustrated as follows: nCO+2nH2->CnH2n+1OH+(n-1)H2O (7) where n is a whole number. According to the present invention, the fuel alcohol synthesis reaction or reactions optionally are catalyzed using a fuel alcohol synthesis catalyst, preferably containing a metal atom, optionally with a halogen promoter. Many metal compounds and promoters can be used. Optionally, secondary activators or ligands may be used in conjunction with the metal catalysts and promoters. These secondary activators can be other metallic salts or compounds, amines, phosphorus compounds, as well as a multitude of other compounds that have been disclosed in the published literature. Thus, a typical catalyst system for the synthesis of fuel alcohol comprises a metal atom-containing catalyst, a promoter and optionally ligands, solvents and/or secondary activators. A variety of references disclose the synthesis of fuel alcohol from syngas. See, for example, (i) El Sawy, A. H., DOE report DE90010325 and references therein, the entireties of which are incorporated herein by reference; (ii) Courty, Charmette, Raimbault and Travers, Rev. De Institute du Petrole, vol. 45(4), 561-578 (1990), the entireties of which are incorporated herein by reference; and (iii) Klier, Herman, Simmons and Lyman, DOE report DE89009888 and references therein, the entireties of which are incorporated herein by reference. Fuel alcohol synthesis may occur at a variety of reaction conditions. In one embodiment, the fuel alcohol synthesis reaction temperature in the fuel alcohol synthesis zone ranges from about 200° C. to about 500° C., preferably from about 250° C. to about 450° C., and most preferably from about 300° C. to about 400° C. The pressure in the fuel alcohol synthesis zone also may vary widely, although the pressure preferably is in the range of the pressure of the syngas that is directed to the methanol synthesis unit, discussed above. Optionally, the pressure in the fuel alcohol synthesis zone ranges from about 5 to about 20 MPa, preferably from about 6 to about 18 MPa, and most preferably from about 10 to about 15 MPa. Although many different fuel alcohol synthesis catalysts may be utilized in the fuel alcohol synthesis zone to facilitate conversion of the syngas contained therein to fuel alcohol, the fuel alcohol synthesis catalyst preferably comprises a microporous zeolitic material. Thus, in one embodiment, the fuel alcohol is formed by contacting syngas with a fuel alcohol synthesis catalyst comprising a microporous zeolitic material under conditions effective to convert the syngas to fuel alcohol, which is contained in a fuel alcohol-containing stream. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises copper and an oxide of zinc. Additionally, in this embodiment, the fuel alcohol synthesis catalyst preferably comprises an oxide of one or both of chromium and/or aluminum. Specifically, in this embodiment, the fuel alcohol synthesis catalyst preferably comprises one or more of Cu/ZnO/ Cr2O3 and Cu/ZnO/Al2O3. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali promoted. Thus, the fuel alcohol optionally is formed in this aspect of the invention by contacting syngas with a fuel alcohol synthesis catalyst comprising one or more of Cu/ZnO/Cr2O3 and Cu/ZnO/Al2O3, which fuel alcohol synthesis catalyst optionally is alkali promoted, under conditions effective to convert the syngas to the fuel alcohol. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises an oxide of one or more of zinc, chromium, copper, cobalt, and nickel. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali, lanthanum or cerium promoted. Thus, the fuel alcohol optionally is formed in this aspect of the invention by contacting syngas with a fuel alcohol synthesis catalyst under conditions effective to convert the syngas to the fuel alcohol, wherein the fuel alcohol synthesis catalyst comprises an oxide of one or more of zinc, chromium, copper, cobalt, and nickel, which fuel alcohol synthesis catalyst optionally is alkali, lanthanum or cerium promoted. Additionally or alternatively, the fuel alcohol synthesis catalyst comprises a compound comprising molybdenum and preferably sulfur. In this embodiment, it is preferred that the fuel alcohol synthesis catalyst is alkali promoted. Specifically, the fuel alcohol optionally is catalyzed by one or more of MoS2 and Co/MoS2. Thus, the fuel alcohol can be formed by contacting syngas with a fuel alcohol synthesis catalyst under conditions effective to convert the syngas to the fuel alcohol, wherein the fuel alcohol synthesis catalyst comprises one or more of MoS2 and Co/MoS2, and wherein the fuel alcohol synthesis catalyst optionally is alkali promoted. The alkali metal atom component of the catalyst system can come from any of the known ionic compounds of the alkali metals sodium, potassium, lithium, rubidium and cesium. Preferred alkali metal atom components are derived from sodium salts and potassium salts. Illustrative sources thereof include sodium iodide, sodium bicarbonate, sodium carbonate, sodium nitrate, sodium nitrite, sodium sulfate, sodium bisulfate, sodium chromate, sodium permanganate, sodium chlorate, sodium persulfate, sodium tetraborate, sodium bromide, sodium chloride, sodium fluoride, sodium sulfite, sodium hypochlorite, as well as any other ionic salt of sodium. Rather than repeat the individual compound names, the corresponding potassium, lithium, rubidium and cesium salts are illustrative of useful ionic compounds. The concentration of alkali metal atoms in the fuel alcohol synthesis zone optionally is from about 0.00013 to about 1 mole per liter; preferably from about 0.07 to about 0.6 mole per liter. Preferably, hydrogen and carbon monoxide are present in the syngas that is directed to the fuel alcohol synthesis zone. The

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molar ratio of H2:CO in the syngas that is directed to the fuel alcohol synthesis zone can vary from about 20:1 to about 1:20, from about 10:1 to about 1:10, and preferably from about 3:1 to about 1:3. Particularly in continuous operations, but also in batch experiments, the carbon monoxide-hydrogen gaseous mixture may also be used in conjunction with up to 50percent by volume of one or more other gases. These other gases may include one or more inert gases such as nitrogen, argon, neon and the like, or they may include gases that may, or may not, undergo reaction under CO hydrogenation conditions, such as carbon dioxide, hydrocarbons such as methane, ethane, propane and the like, ethers such as dimethyl ether, methylethyl ether and diethyl ether, alkanols such as methanol and acid esters such as methyl acetate. According to the present invention, a fuel alcohol-containing stream is formed, which comprises the fuel alcohol. The fuel alcohol-containing stream preferably comprises two or more alcohols in the C2 to C5 range. Higher alcohols and carboxylic acid esters may also be formed while carrying out the process of this invention. For example, the fuel alcohol-containing stream may include methyl formate, methyl acetate, ethyl acetate, ethyl ether. The major by-products of the process such as the higher molecular weight alcohols and carboxylic acid esters, are, of course, also useful compounds and major articles of commerce. The higher alcohols, the carboxylic acid esters and ethers can easily be separated from one another by conventional means, e.g., fractional distillation in vacuo, if desired. The precise amount and type of components contained in the fuel alcohol-containing stream will vary widely depending on catalyst type, reaction conditions, and syngas composition used. For example, Table I, below, provides three catalyst systems and indicates exemplary product yields and operating conditions. See El Sawy, A. H., DOE report DE90010325, pp. 3-17, 3-18. Product Yields (Wt. percent) and Reaction Conditions of Three Fuel Alcohol Synthesis Systems Process Product Slate Main Catalyst Constituents (anhydrous basis) Cu/Co/Al Zn/Cr/K Cu/ZnO/Al Methanol 57.5 70.0 64.5 Ethanol 28.5 2.5 11.5 C3 alcohols 7.1 3.4 5.2 C4 alcohols 2.8 12.5 7.4 C5+ alcohols 2.5 9.5 7.4 Hydrocarbons 0.3 - 0.02 Esters 0.7 0.1 0.8 Other Oxygenated 0.6 2.0 3.18 Products Total Alcohols 98.4 97.9 96.0 Operating T (° C.) 260-320 350-420 285-300 Operating Pressure 6-10 10-18 6-9 (MPa) Syngas Feed Ratio 2.0-2.5 1.5-2 0.5-1 (H2:CO)Syngas CO2 0.5-3.0 2-6 1.0 Content (Vol. percent) As indicated by Table I, the amount of ethanol contained in the fuel alcohol-containing stream may vary. The fuel alcohol-containing stream preferably comprises at least about 10 weight percent ethanol, more preferably at least about 25 weight percent ethanol and most preferably at least about 35 weight percent ethanol, based on the total weight of the fuel alcohol-containing stream. In terms of ranges, the fuel alcohol-containing stream optionally comprises on the order of from about 5 to about 60 weight percent ethanol, preferably from about 10 to about 50 weight percent ethanol, and most preferably from about 20 to about 40 weight percent ethanol, based on the total weight of the fuel alcoholcontaining stream. The fuel alcohol-containing stream also comprises one or more C3 alcohols, preferably on the order of from about 5 to about 80 weight percent C3 alcohols, preferably from about 10 to about 60 weight percent C3 alcohols, and most preferably from about 15 to about 40 weight percent C3 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C3 alcohols comprise one or more of 1-propanol, 2-propanol, and/or 1,2-propadiol. Additionally or alternatively, the fuel alcohol-containing stream comprises one or more C4 alcohols, preferably on the order of from about 0.1 to about 20 weight percent C4 alcohols, preferably from about I to about 10 weight percent C4 alcohols, and most preferably from about 2 to about 5 weight percent C4 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C4 alcohols comprise one or more of I -butanol; 2-butanol; 1,4-butanediol; 1,3-butanediol; 1,2-butanediol; isobutyl alcohol; sec-butyl alcohol; and t-butyl alcohol. The fuel alcohol-containing stream preferably comprises at least about 5 weight percent C3-C4 alcohols, more preferably at least about 10 weight percent C3-C4 alcohols, and most preferably at least about 15 weight percent C3-C4 alcohols. Optionally, the fuel alcohol-containing stream comprises one or more C5 alcohols, preferably on the order of from about 0.01 to about 10 weight percent C5 alcohols, preferably from about 0.1 to about 5 weight percent C5 alcohols, and most preferably from about 0.1 to about 3 weight percent C5 alcohols, based on the total weight of the fuel alcohol-containing stream. Optionally, the C5 alcohols comprise one or more of 1-pentanol; 2-pentanol; 3pentanol; 1,5-pentanediol; 1,4-pentanediol; 1,3-pentanediol; and 1,2-pentanediol. Additionally, the fuel alcohol-containing stream optionally comprises one or more C6+ alcohols, preferably on the order of from about 0.01 to about 10 weight percent C6+ alcohols, preferably from about 0.1 to about 5 weight percent C6+ alcohols, and most preferably from about 0.1 to about 3 weight percent C6+ alcohols, based on the total weight of the fuel alcohol-containing stream. Ideally, the fuel alcohol-containing stream contains low amounts of methanol, if any. Preferably, the fuel alcohol-containing stream comprises less than 75 weight percent methanol, more preferably less than 65 weight percent methanol, and most preferably less than 60 weight percent methanol, based on the total weight of the fuel alcohol-containing stream. In terms of weight ratios, if the fuel alcohol-containing stream comprises methanol and ethanol, then the weight ratio of methanol to ethanol ranges from about 1 to about 6, more preferably from about 1.5 to about 5, and most preferably from about 2 to about 4. If the fuel alcohol-containing stream comprises ethanol and C3 alcohols, then the weight ratio of ethanol to C3 alcohols preferably ranges from about 1 to about 30, more preferably from about 5 to about 30, and most preferably from about 10 to about 20. The novel process of this invention can be conducted in a batch, semi-continuous or continuous fashion. The catalyst may be initially introduced into the fuel alcohol synthesis zone batchwise, or it may be continuously or intermittently introduced into such a zone during the course of the synthesis reaction. Operating conditions can be adjusted to optimize the formation of the fuel alcohol product, and after recovery of the alcohol and other products, a fraction rich in the catalyst composition may then be recycled to the reaction zone, if desired, and additional products generated. A non-limiting list of preferred reactor

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types for the synthesis of fuel alcohol includes fixed bed, slurry reactors and fluid bed reactors. One can additionally have an inert solvent present in the reaction mixture. A wide variety of substantially inert solvents are useful in the process of this invention including hydrocarbon and oxygenated hydrocarbon solvents. Suitable oxygenated hydrocarbon solvents are compounds comprising carbon, hydrogen and oxygen and those in which the only oxygen atoms present are in ether groups, ester groups, ketone carbonyl groups or hydroxyl groups of alcohols. Generally, the oxygenated hydrocarbon will contain 3 to 12 carbon atoms and preferably a maximum of 3 oxygen atoms. The solvent preferably is substantially inert under reaction conditions, is relatively non-polar and has a normal boiling point of at least 65° C. at atmospheric pressure, and preferably, the solvent will have a boiling point greater than that of ethanol and other oxygen-containing reaction products so that recovery of the solvent by distillation is facilitated. Preferred ester type solvents are the aliphatic and acylic carboxylic acid monoesters as exemplified by butyl acetate, methyl benzoate, isopropyl iso-butyrate, and propyl propionate as well as dimethyl adipate. Useful alcohol-type solvents include monohydric alcohols such as cyclohexanol, 1-hexanol, 2-hexanol, neopentanol, 2-octanol, etc. Suitable ketone-type solvents include, for example, cyclic ketones such as cyclohexanone, 2-methylcyclohexanone, as well as acylic ketones such as 2-pentanone, butanone, acetophenone, etc. Ethers that may be utilized as solvents include cyclic, acyclic and heterocyclic materials. Preferred ethers are the heterocyclic ethers as illustrated by 1,4-dioxane and 1,3-dioxane. Other suitable ether solvents include isopropyl propyl ether, diethylene glycol dibutyl ether, dibutyl ether, ethyl butyl ether, diphenyl ether, heptyl phenyl ether, anisole, tetrahydrofuran, etc. The most useful solvents of all of the above groups include the ethers as represented by monocyclic, heterocyclic ethers such a 1,4-dioxane or p-dioxane, etc. Hydrocarbon solvents, such as hexane, heptane, decane, dodecane, tetradecane, etc. are also suitable solvents for use in this invention. In the practice of this invention, it is also possible to add a small amount of water to the solvent and still obtain satisfactory results. The reaction time varies depending upon the reaction parameters, reactor size and charge, and the individual components employed at the specific process conditions. With hydrogen, Zn/Cr/K, T= 350 - 420 °C , p= 75007.5 - 135014Torr , Conversion of starting material Patent; Janssen, Marcel Johannes; Van Egmond, Cornelis F.; Martens, Luc R.M.; Sher, Jaimes; US2005/107481; (2005); (A1) English View in Reaxys

2-[4-[(6-fluoro-1,2-benzisoxazol-3yl)-1-piperidinyl]ethyl]amine

2 O

–O

K+

O–

2-[2-[4-(6,Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate

Rx-ID: 24644736 View in Reaxys 76/630 Yield

Conditions & References 132 : 2-[2-[4-(6,Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate EXAMPLE 132 2-[2-[4-(6,Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate A mixture of 2-[4-[(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amine (2.0 g, 7.6 mmol), K2 CO3 (1.38 g, 10 mmol) and bromoethyl acetate (1.40 g, 8.3 mmol) in acetonitrile (50 ml) was heated at reflux for 4 hours. At the end, the insolubles were filtered off and rinsed with DCM. The solvent was evaporated down. The crude mixture was purified by flash chromatography over a silica gel column (Sorbsil C-30, 30 g; eluted with 2percent CH3 OH in DCM, 800 ml). The oil (1.15 g) thus obtained was treated with a solution of fumaric acid (358 mg) in ethanol. Crystallization was induced by adding drops of ethyl ether, yield: 1.09 g, m.p.=116°-118° C. Analysis: Calculated for C18 H24 FN3 O3.C4 H4 O4: 56.77percent C 6.06percent H 9.03percent N Found: 56.32percent C 5.97percent H 8.94percent N in ethanol, 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran, acetonitrile Patent; Hoechst Roussel Pharmaceuticals, Inc.; US5605913; (1997); (A1) English View in Reaxys

(v2)

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Ti2+

O–

Ti2+

O–

Rx-ID: 27086712 View in Reaxys 77/630 Yield

Conditions & References

89 %, 85 %

With acetone in toluene, argon atmosphere or vac.; acetone addn. to Ti-complex soln.; solvent removal after 5 h, residue vac.-drying (20°C, 1E-3 mm Hg); elem. anal. Razuvaev, G. A.; Vyshinskaya, L. I.; Vasil'eva, G. A.; Malysheva, A. V.; Rabinovich, A. M.; Journal of General Chemistry USSR (English Translation); vol. 52; (1982); p. 1178 - 1184; Zhurnal Obshchei Khimii; vol. 52; (1982); p. 1338 - 1345 ; (from Gmelin) View in Reaxys O

Rx-ID: 30435770 View in Reaxys 78/630 Yield

Conditions & References 8 :Operating Conditions for the Selective Oxidation of EthanolThe catalyst was tested in a fixed-bed reactor. The flow rates of helium and of oxygen were controlled by a mass flow meter. The gas mixture passed through an evaporator/saturator filled with ethanol. The evaporator was either at ambient temperature or heated by a heater cable. The temperature of the saturator was adjusted and controlled in order to obtain the desired partial pressure of ethanol. The temperature was measured using a thermocouple at the outlet of the saturator.The reaction mixture fed the reactor, which was placed in an oven. The reaction temperature was measured by a thermocouple placed in the catalytic bed.The gaseous effluents were analysed in-line by gas chromatography using a MicroGC equipped with three columns (molecular sieve, Plot U and OV-1).A stream of helium and oxygen passed through the evaporator/saturator, which were adjusted to suitable temperatures that made it possible to obtain the desired ethanol/oxygen/helium composition. The catalyst was mixed with a quadruple amount of silicon carbide in the glass reactor.Calibration of the MicroGC was carried out with reference gas mixtures, and the condensable products were calibrated using the evaporator/saturator. EXAMPLE 8According to the Invention150 mg of the MFM3-MS catalyst (supplied by MAPCO) were mixed with 600 mg of silicon carbide and were charged into the reactor.The catalyst was activated at a temperature of 340° C. under a helium/oxygen mixture (48 Nml*min-1/12 Nml*min-1) for 12 hours. Next, the temperature was decreased to 200° C. and the data were recorded. After stabilization, the efficiency of the catalyst was tested. After acquisition of the data, the temperature of the catalyst was increased to the following temperature: 200° C. then 230° C. and 260° C., where the data were recorded.The flow rates of oxygen and helium were respectively 4.6 and 41 Nml*min-1 and the temperature of the saturator was adjusted to obtain a molar fraction of ethanol of 30percent, ethanol/O2/He=30/7/63. 500 ppm (vol) of SO2 were added to the gas stream.The results as regards the conversions and selectivities obtained during the catalytic oxidation of ethanol, expressed as follows: A=acetaldehyde; DEE=1,1diethoxyethane; EE=ethyl ether; EA=ethyl acetate; AA=acetic acid; E=ethylene; CO=carbon monoxide; CO2=carbon dioxide, are given in table 3. With sulfur dioxide, oxygen, α6H-SiC, T= 260 °C , Inert atmosphere, Gas phase, Product distribution / selectivity Patent; Arkema France; US2011/71322; (2011); (A1) English View in Reaxys

I O

Rx-ID: 40975852 View in Reaxys 79/630 Yield

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nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. , Time= 5h, T= 170 °C , p= 760.051Torr , Flow reactor Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys 2.3. Ethanol carbonylation flow reactor General procedure: Gas-phase reactions were carried out in quartz down flow microreactors in an Altamira Instruments BenchCAT 4000R-HP. Mixtures of ethanol and ethyl iodide co-catalyst were delivered via liquid syringe pump (KD Scientific KDS-100) at total liquid flow rates of 2-5 lL/min. The ethanol-to-ethyl iodide ratio was controlled in the range of 5-100:1. The liquid feed was vaporized in line with CO reactant. CO-to-ethanol molar ratios varied from 2 to 18:1, and CO flow rates were varied between 5 mL/min and 30 mL/min. The catalyst bed consisted of 0.1–1.5 g of catalyst held in place by quartz wool, and the reactions were conducted at reactor temperatures of 150–210 °C and nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. With 1 wtpercent Rh/Na13X zeolite catalyst, Time= 5h, T= 170 °C , p= 760.051Torr , Flow reactor, Catalytic behavior, Concentration, Pressure Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys 2.3. Ethanol carbonylation flow reactor General procedure: Gas-phase reactions were carried out in quartz down flow microreactors in an Altamira Instruments BenchCAT 4000R-HP. Mixtures of ethanol and ethyl iodide co-catalyst were delivered via liquid syringe pump (KD Scientific KDS-100) at total liquid flow rates of 2-5 lL/min. The ethanol-to-ethyl iodide ratio was controlled in the range of 5-100:1. The liquid feed was vaporized in line with CO reactant. CO-to-ethanol molar ratios varied from 2 to 18:1, and CO flow rates were varied between 5 mL/min and 30 mL/min. The catalyst bed consisted of 0.1–1.5 g of catalyst held in place by quartz wool, and the reactions were conducted at reactor temperatures of 150–210 °C and nominally at atmospheric pressure. No pretreatment was performed on the catalyst bed unless otherwise stated. Weight hourly space velocities (WHSVs) were obtained from total mass flow rate divided by mass of catalyst. , Time= 5h, T= 170 °C , p= 760.051Torr , Flow reactor, Catalytic behavior, Reagent/catalyst Yacob, Sara; Park, Sunyoung; Kilos, Beata A.; Barton, David G.; Notestein, Justin M.; Journal of Catalysis; vol. 325; (2015); p. 1 - 8 View in Reaxys

Rx-ID: 41795654 View in Reaxys 80/630 Yield

Conditions & References Ethanol (analytical grade, GOST 596493) was used without preliminary purification. Ethanol conversion was studied on a PID Eng&Tech microcatalytic batch setup with the stationary catalyst bed17 in the reactor volume (10 cm3 volume) (9.12 mm internal diameter, 153 mm length). The catalyst samples of 10cm3 were used. Ethanol conversion was studied under optimum conditions8: inargon at a pressure of 5 atm, temperature330°C, and space velocity of the substrate 0.6 h–1. Gaseous reaction products were analyzed on line on a gas chromatograph,and hydrocarbon gases 1—5 were analyzedon a Kristall-4000M chromatograph (flame ionization detector, HP PLOT/Al2O3 column). The content of , 2, and 2 was determinedon a Kristall-4000 chromatograph (thermal conductivity detector, CKT column). and low CO concentrations(<0.4 vol.percent) were determined using a Riken-Keiki gas analyzerwith the IRcell (model RI 550A). Liquid organic reaction products in the aqueous and organic phases were identified by the MS/GC method using MSD 6973 (Agelent) and Automass150 (Delsi Nermag) instruments with an ionization energy of 70 eV and asample volume of 1 L. The quantitativecontent of organic substances was determined by GLC on a Varian 3600 instrument. The content of ethanol in the aqueous phase was determined using MS/GC from the ratio of integralsignals of alcohol and water by the absolute calibration method. With Re—W/Al2O3, T= 330 °C , p= 3800.26Torr , Catalytic behavior, Reagent/catalyst

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Zharova; Chistyakov; Zavelev; Kriventsov; Yakimchuk; Kryzhovets; Petrakova; Drobot; Tsodikov; Russian Chemical Bulletin; vol. 64; nb. 2; (2015); p. 337 - 345; Izv. Akad. Nauk, Ser. Khim.; vol. 64; nb. 2; (2015); p. 337 345,9 View in Reaxys OH

Rx-ID: 7053546 View in Reaxys 81/630 Yield

Conditions & References With sulfuric acid, T= 130 °C , und Gleichgewicht Pease; Yung; Journal of the American Chemical Society; vol. 46; (1924); p. 2400 View in Reaxys With aluminum oxide, T= 250 °C , Gleichgewicht Clark; Graham; Winter; Journal of the American Chemical Society; vol. 47; (1925); p. 2753 View in Reaxys With aluminum oxide, T= 275 °C , Gleichgewicht Pease; Yung; Journal of the American Chemical Society; vol. 46; (1924); p. 2400 View in Reaxys With sulfuric acid, wird das gebildete Wasser mit dem Aether zugleich abdestilliert Williamson; Justus Liebigs Annalen der Chemie; vol. 81; (1852); p. 77 View in Reaxys Williamson; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 40; (1854); p. 98; Justus Liebigs Annalen der Chemie; vol. 77; (1851); p. 38 View in Reaxys With potassium alum, T= 215 - 233 °C , Gleichgewicht Jatkar; Watson; Journal of the Indian Institute of Science, Section A; vol. 9; p. 106; Chem. Zentralbl.; vol. 97; nb. II; (1926); p. 2767 View in Reaxys T= 120 - 236 °C , Gasphase, Equilibrium constant Valentin; Journal of the Chemical Society; (1950); p. 498 View in Reaxys

OH O

2 O

–O

K+

O–

NH O

Rx-ID: 25032870 View in Reaxys 82/630 Yield

Conditions & References 6.d : (d) (d) 3,3-Dimethyl-6-ethoxy-indolin-2-one (starting material): 8.3 g of the product of step (c), 38.8 g K2 CO3 and 22.7 ml ethyl iodide in 300 ml acetone are heated under reflux for 24 hours. The obtained reaction mixture is filtered and evaporated and the residue taken up in ethyl acetate. The title compound is obtained after shaking 2x with water, drying over Mg2 SO4, concentration and dilution with ethyl-ether: M.P.=175°-176° C. in ethyl acetate, acetone Patent; Sandoz Ltd.; US4622336; (1986); (A1) English View in Reaxys

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(v2)

Rx-ID: 27086709 View in Reaxys 83/630 Yield

Conditions & References

84 %, 87 %

With benzophenone in toluene, argon atmosphere or vac.; benzophenone addn. to Zr-complex soln.; solvent removal after 5 h, residue vac.-drying (20°C, 1E-3 mm Hg); elem. anal. Razuvaev, G. A.; Vyshinskaya, L. I.; Vasil'eva, G. A.; Malysheva, A. V.; Rabinovich, A. M.; Journal of General Chemistry USSR (English Translation); vol. 52; (1982); p. 1178 - 1184; Zhurnal Obshchei Khimii; vol. 52; (1982); p. 1338 - 1345 ; (from Gmelin) View in Reaxys

F F

F P–

FF F

F F FF F

O+

Cl –

N+

F F

F P–

F F

N+

F F F

Rx-ID: 28129754 View in Reaxys 84/630 Yield 98.9 %

Conditions & References 10 :Example 101-Ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate A mixture of 1.12 g (7.64 mmol) of 1-ethyl-3-methylimidazolium chloride and 4.19 g (7.64 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 70-80° C. (temperature of the oil bath) and stirred for three hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 70° C. (temperature of the oil bath), giving 4.20 g of a liquid. The yield of 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate is 98.9percent, based on the 1-ethyl-3-methylimidazolium chloride employed. The product is investigated by NMR spectroscopy.1H NMR spectrum, ppm: 1.47 t (CH3), 3.84 s (CH3), 4.18 q (CH2), 7.34 m (CH), 7.39 m (CH), 8.43 br. s. (CH); J3 H,H=7.3 Hz.19F NMR spectrum, ppm: -43.54 dm (PF), -79.60 m (CF3), -81.29 m (2CF3), -86.96 dm (PF2), -115.03 dm (CF2), -115.55 dm (2CF2); J1 P,F=889 Hz, J1 P,F=906 Hz, J2 P,F=84 Hz, J2 P,F=106 Hz.31P NMR spectrum, ppm: -149.0 d,t,m. , Time= 3h, T= 80 °C , Product distribution / selectivity Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys

(v3)

6Li (v3) (v5)

(v3) 6Li (v5)

(v3)

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(v3)

6Li

(v2)

6Li

(v3) (v3) 6Li (v5)

(v3)

(v5)

(v3)

Rx-ID: 28680815 View in Reaxys 85/630 Yield

Conditions & References in deuterated toluene, T= -70 °C Knorr, Rudolf; Menke, Thomas; Ferchland, Kathrin; Mehlstaeubl, Johann; Stephenson, David S.; Journal of the American Chemical Society; vol. 130; nb. 43; (2008); p. 14179 - 14188 View in Reaxys O

Rx-ID: 33032255 View in Reaxys 86/630 Yield

Conditions & References With TiF4 in chloroform-d1, dichloromethane, Time= 96h, T= 24.84 °C Marchetti, Fabio; Pampaloni, Guido; Biancalana, Lorenzo; Inorganica Chimica Acta; vol. 385; (2012); p. 135 139 View in Reaxys

Rx-ID: 40651640 View in Reaxys 87/630 Yield

Conditions & References

21.6 %

With Hf(3.0 wtpercent)Zn(0.5 wtpercent)-silica supported catalyst, Time= 3.5h, T= 300 - 360 °C , Reagent/catalyst De Baerdemaeker, Trees; Feyen, Mathias; Müller, Ulrich; Yilmaz, Bilge; Xiao, Feng-Shou; Zhang, Weiping; Yokoi, Toshiyuki; Bao, Xinhe; Gies, Hermann; De Vos, Dirk E.; ACS Catalysis; vol. 5; nb. 6; (2015); p. 3393 3397 View in Reaxys

FF F F

F F N+

F (v5)

(v5)F

F F

(v5)

F (v5)

F F

F (v5)F

F F

Pt–

(v6)

N F

(v3)

N+

(v6)

FF F F

F (v2) Pt–

(v6)

F F

(v2)

(v3)

Ag N

F F

(v4)

F F

Rx-ID: 26406230 View in Reaxys 88/630 Yield 79 %

Conditions & References in dichloromethane, Addn. to a CH2Cl2 soln. of Pt-compd. of an equimolar amt. of PPh3 and stirring of mixt. (exclusion of light, room temp., 30 min).; Evapn. of soln. to dryness.

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Uson, Rafael; Fornies, Juan; Tomas, Milagros; Casas, Jose M.; Cotton, Albert F.; et al.; Organometallics; vol. 7; (1988); p. 2279 - 2285 ; (from Gmelin) View in Reaxys F

-1

F F FF F

F P–

F F FF F

O+

(v4)

B FF

N+

F F

P–

N+ F

F B

Rx-ID: 28129750 View in Reaxys 89/630 Yield

Conditions & References

90.3 %

11 :Example 111-Ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate A mixture of 0.54 g (2.73 mmol) of 1-ethyl-3-methylimidazolium tetrafluoroborate and 1.50 g (2.74 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 100° C. (temperature of the oil bath) and stirred for ten hours under a nitrogen atmosphere. Volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 100° C. (temperature of the oil bath), giving 1.37 g of a liquid. The yield of 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate is 90.3percent, based on the 1-ethyl-3-methylimidazolium tetrafluoroborate employed. The product is investigated by NMR spectroscopy.NMR data: see Example 10 , Time= 10h, T= 100 °C , Product distribution / selectivity Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys

-1

F F FF F

F P–

F F FF F

O+

CH + N

F F (v6) F P F F F

F F F

F F

P–

F F

N+

F F

P FF F

Rx-ID: 28129752 View in Reaxys 90/630 Yield

Conditions & References

98.7 %

12 :Example 121-Ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate A mixture of 1.73 g (6.75 mmol) of 1-ethyl-3-methylimidazolium hexafluoro-phosphate and 3.70 g (6.75 mmol) of triethyloxonium tris(pentafluoroethyl)trifluorophosphate from Example 1 is heated to 100° C. (temperature of the oil bath) and stirred for ten hours under a nitrogen atmosphere. The volatile constituents are pumped off over the course of one hour under reduced pressure (7 Pa) at 100° C. (temperature of the oil bath), giving 3.71 g of a liquid. The yield of 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate is 98.7percent, based on the 1-ethyl-3-methylimidazolium hexafluorophosphate employed. The product is investigated by NMR spectroscopy.NMR data: see Example 10 , Time= 10h, T= 100 °C , Product distribution / selectivity Patent; Ignatyev, Nikolai (Mykola); Bissky, German; Willner, Helge; US2009/36628; (2009); (A1) English View in Reaxys

OH O

Rx-ID: 29884456 View in Reaxys 91/630

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Yield

Conditions & References With oxygen, T= 400 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys

Rx-ID: 29884458 View in Reaxys 92/630 Yield

Conditions & References With Li2O/mixed oxides of ceria on alumina support, T= 400 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys O

Rx-ID: 33032256 View in Reaxys 93/630 Yield

Conditions & References Stage 1: With TiF4 in chloroform-d1, dichloromethane, T= 80 °C Stage 2: With water, Time= 1h, T= 24.84 °C Marchetti, Fabio; Pampaloni, Guido; Biancalana, Lorenzo; Inorganica Chimica Acta; vol. 385; (2012); p. 135 139 View in Reaxys

Rx-ID: 38876420 View in Reaxys 94/630 Yield

Conditions & References With water, Time= 6h, T= 500 °C , p= 760.051Torr , Flow reactor Marcos; Lucrdio; Assaf; RSC Advances; vol. 4; nb. 83; (2014); p. 43839 - 43849 View in Reaxys OH

Rx-ID: 40651642 View in Reaxys 95/630 Yield

Conditions & References With Hf(3.0 wtpercent)-silica supported catalyst, Time= 3.5h, T= 300 - 360 °C , Reagent/catalyst De Baerdemaeker, Trees; Feyen, Mathias; Müller, Ulrich; Yilmaz, Bilge; Xiao, Feng-Shou; Zhang, Weiping; Yokoi, Toshiyuki; Bao, Xinhe; Gies, Hermann; De Vos, Dirk E.; ACS Catalysis; vol. 5; nb. 6; (2015); p. 3393 3397 View in Reaxys

2-amino-Δ2 -oxazolin-4-one

HO O

Rx-ID: 24973577 View in Reaxys 96/630 Yield

Conditions & References 8.B : 2-Dimethylamino-Δ2 -oxazolin-4-one Ethyl glycolate (50.2 g, 0.48 mol) was added to the reaction mixture dropwise over 1 hr. and the mixture was allowed to stir overnight at room temperature. The desired 2-amino-Δ2 -oxazolin-4-one (42.3 g, 88percent) was collected by filtration and triturated with ethanol and then with diethylether: mp 245°-246° C. 2-Amino-Δ2 -oxazolin-4-one (5.0 g, 50 mmol) was slurried in ethanol (100 ml) at 60° C.

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Patent; Pfizer Inc.; US4584385; (1986); (A1) English View in Reaxys

(v5) (v5) (v5) (v5)

S P

(v3)

Yb O

(v11)

(v5) (v5) (v5)(v5)

(v5) (v5) (v5) (v5)

S S (v5) Yb (v11)P

(v5) (v5) (v5)

Rx-ID: 26367971 View in Reaxys 97/630 Yield

Conditions & References

96 %

in toluene, stirring, 2 h, under N2; concn., cooling to -10°C; elem. anal. Berg, David J.; Andersen, Richard A.; Zalkin, Allan; Organometallics; vol. 7; (1988); p. 1858 - 1863 ; (from Gmelin) View in Reaxys

OH O

Rx-ID: 29884457 View in Reaxys 98/630 Yield

Conditions & References With oxygen, T= 300 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys

Rx-ID: 29884459 View in Reaxys 99/630 Yield

Conditions & References With oxygen, T= 400 °C , p= 760.051Torr , Inert atmosphere Lippits; Nieuwenhuys; Catalysis Today; vol. 154; nb. 1-2; (2010); p. 127 - 132 View in Reaxys Rx-ID: 38624232 View in Reaxys 100/630

Yield

Conditions & References 17 : Example 9 Conversion of Ethanol to n-Butanol Using a Ca-Pyrophosphate/Cu Catalyst Example 17 Direct Synthesis of Higher Alcohols from Ethanol [0198] Catalysts were tested for higher alcohol synthesis reactions in a fixed bed reactor operating at about 200-300° C. and about 1-35 atm. Catalysts were reduced in a stream of H2 at a temperature between 175° C. and 240° C. prior to use in reactions. [0199] Table 11 shows the reactor effluent composition using two different supported catalysts at different temperatures. The first catalyst was a mixture of CuO and MgO co-impregnated onto a SiO2 support and the second was CuO, ZrO2 and Al2O3 co-impregnated onto an Al2O3 support. The reactor effluent composition shown in Table 11 resulted from the use of 5.0 g catalyst with a 0.10 ml/min ethanol feed at 500 psig. As expected, increasing temperature also increased the conversion of ethanol to higher alcohols. Significant amounts of acetaldehyde and butyraldehyde were also observed, but no crotonaldehyde was observed in the reactor effluent. In Table 11, the “hexanols” include both 1-hexanol and 2-ethyl butanol, and the “octanols” include 1-octanol and 2-ethyl hexanol. 0200] FIG. 13 shows a typical product distribution from the CuO/MgO on SiO2 catalyst. Including the intermediates acetaldehyde and butyraldehyde along with all of the product alcohols, the overall reaction selectivity is above 85percent (the percent of the total ethanol consumed that is converted into the desired product or reaction intermediates). Other reaction products include mostly esters such as ethyl acetate, butyl acetate, and ethyl butyrate, although some 2-butanone and 2-butanol are also present in the reactor effluent. The product distribution using the CuO/ZrO2/Al2O3 on Al2O3 catalyst, shown in FIG. 14, displays a similar breakdown of reaction byproducts, except a significant amount of diethyl ether is produced over this catalyst.

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With CuO/ZrO2 on Al2O3 , hydrogen, T= 300 °C , Temperature Patent; Greenyug, LLC; GADEWAR, Sagar B.; VICENTE, Brian Christopher; STOIMENOV, Peter K.; JULKA, Vivek; US2014/235901; (2014); (A1) English View in Reaxys O– K+

I O

Rx-ID: 631701 View in Reaxys 101/630 Yield

Conditions & References With ammonia White; Morrison; Anderson; Journal of the American Chemical Society; vol. 46; (1924); p. 967 View in Reaxys O

O O O

Rx-ID: 758063 View in Reaxys 102/630 Yield

Conditions & References With methanol, boron trifluoride, mercury(II) oxide, anschliessend Behandeln mit Pentin-(1) und Erwaermen des Reaktionsgemisches auf Siedetemperatur Hennion; Nieuwland; Journal of the American Chemical Society; vol. 56; (1934); p. 1802 View in Reaxys O

Rx-ID: 1895930 View in Reaxys 103/630 Yield

Conditions & References With water, pentasil zeolite in gas, T= 200 °C , p= 3677.5Torr , other pressure, other temp., other catalyst, Product distribution Eguchi, Koichi; Tokiai, Takeo; Kimura, Yoshio; Arai, Hiromichi; Chemistry Letters; (1986); p. 567 - 570 View in Reaxys

Rx-ID: 23228637 View in Reaxys 104/630 Yield

Conditions & References 1; 2; 3 :The catalyst employed was 12-tungstosilicic heteropolyacid supported on Grace 57 silica at a catalyst loading of 140 grams per litre. The experiment involved start-up and initial operation within standard parameters to obtain a steady baseline activity and impurity make rates. The total system pressure was then varied, by adjusting the recycle compressor discharge pressure, while maintaining other variables constant. The shutdown involved taking off feeds, reducing system pressure to atmospheric, and cooling the unit to ambient temperature, using a standard operating procedure designed to protect the catalyst. A summary of the key operating conditions and results is given in Table 1. As can be noted from Table 1, the effect of varying pressure over the experimental range had negligible impact on catalyst productivity of ethyl acetate at a constant reactor inlet temperature. The effect of pressure was also noted to be minor towards the make-rates of the major by-products in the process; namely ethanol and diethyl ether. It will be noted that operation at 9 barg (Comparative Example 3) provides relatively high make-rates of both MEK and acetaldehyde, while operation in accordance with the present invention at, respectively 11 and 13 barg

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(Examples 1 and 2), resulted in significant decrease in the concentrations of both these byproducts. The response to pressure of these materials is displayed on Figure 2 of the Drawings. The make rates of a variety of other minor reaction by-products were also observed to change as a result of changes in the reaction pressure. The reaction produces a range of hydrocarbon impurities at similar levels, at concentrations of up to 1000 ppm in the crude product stream. These impurities range mainly from C4 to C8 carbon numbers in chain length. However, they can grow in chain length up to C20+ upon recycle through the reactor train. These hydrocarbons may take the forms of saturated or unsaturated, branched or linear species; i. e. 2-methylpentane, 3-methylpentane, 2-methylhexane, 2, 3-DIMETHYLPENTANE, 3-methylhexane, trimethylpent-2-ene, and 2-methyl-2-heptene, have all been identified as well as many other analogous species. In comparing analysis of the 9 barg and 13 barg operation product streams, by FID gas chromatography, it is noted that the reduction in these by-products is significant. In the majority of cases, the measured component level at the higher pressure operation represents only 10percent of that obtained at the lower pressure, and in some cases, as low as 1percent. This difference is illustrated by comparison of Figures 3 and 4 which show Gas Chromatograms of the crude product streams. Significant reduction of other oxygenated hydrocarbon by-products also occurs at 13 barg operation, including but not limited to; acetone (reduced by 90percent), ethyl formate (reduced by 90percent), 3-pentanone (reduced by 90percent), and ethyl propionate (reduced by 50percent). Not all of the process impurities in the stream have been identified. The heavier hydrocarbon species, up to C20+, also undergo significant overall reduction at higher pressure, being measured at 40percent of the lower pressure value, also by FID gas chromatography, although no distinction is made between the individual components in this measurement. As the aforementioned impurities predominantly originate from an ethylene precursor, the operation of the process at higher pressure improves the catalyst selectivity based on ethylene by inhibiting the formation of these species. Since the process must typically remove the majority of these components by means of a purge stream, the benefit of higher pressure operation will allow process operation with significant reduction or elimination of some or all of these purge streams. It is reasonable to suppose that further increases in pressure could extend the benefit further. The reductions in acetaldehyde and methyl ethyl ketone for example enable extended catalyst life as this material has previously been identified as a catalyst deactivation precursor. Similarly 2-butanone. The hydrocarbon species will also play a role in catalyst deactivation by providing a source of coke for the catalyst surface and hence providing a barrier between the reactants and the catalyst active sites as coke formation increases. It is therefore believed that significant reduction of these species will allow extension of catalyst life and deliver commercial benefit. With water, 12-tungstosilicic heteropolyacid supported on Grace 57 silica, T= 172 °C , p= 6750.68 - 9750.98Torr , Product distribution / selectivity Patent; BP CHEMICALS LIMITED; WO2005/23747; (2005); (A1) English View in Reaxys

P2Zn 3

H 2O2Zn

Rx-ID: 26361100 View in Reaxys 105/630 Yield

Conditions & References

0 %, 0 %, 0%

With ethanol, oxygen in ethanol, Kinetics, chromy. Dorfman, Ya. A.; Petrova, T. V.; Sagandykova, R. R.; Ibraimova, Zh. U.; Levina, L. V.; Journal of General Chemistry USSR (English Translation); vol. 59; (1989); p. 1291 - 1292; Zhurnal Obshchei Khimii; vol. 59; (1989); p. 1452 1454 ; (from Gmelin) View in Reaxys With ethanol, oxygen, copper dichloride in ethanol, Kinetics, chromy. Dorfman, Ya. A.; Petrova, T. V.; Sagandykova, R. R.; Ibraimova, Zh. U.; Levina, L. V.; Journal of General Chemistry USSR (English Translation); vol. 59; (1989); p. 1291 - 1292; Zhurnal Obshchei Khimii; vol. 59; (1989); p. 1452 1454 ; (from Gmelin) View in Reaxys

(v5) (v5) (v5) (v5)

(v3)

Yb O

(v11)

(v5) (v5) (v5)(v5)

(v5) (v5) (v5)

P P

(v5)

S Yb S P

(v11)

(v5) (v5) (v5)

Rx-ID: 26367970 View in Reaxys 106/630

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Yield

Conditions & References

81 %

OH F F

F O

O S FF

Rx-ID: 26755154 View in Reaxys 107/630 Yield

Conditions & References With NaF, with excess of NaF, 25°C, 3 h Kitazume; Shreeve; Journal of the American Chemical Society; vol. 99; (1977); p. 4194 View in Reaxys Kitazume, T.; Shreeve, J. M.; J. Inorg. Chem.; vol. 17; (1978); p. 2173 - 2176 View in Reaxys vol. F: PerFHalOrg.SVol.3; 6.2.2, page 1 - 48 ; (from Gmelin) View in Reaxys

F HO

SiH

F F

Rx-ID: 31827265 View in Reaxys 108/630 Yield

Conditions & References HFIP: Hexafluoroisopropanol TIPS: triisopropylsilane TFA: trifluoroacetic acid Et2O: diethylether Patent; Novo Nordisk A/S; US2011/275559; (2011); (A1) English View in Reaxys

H 3Si

SiH

Rx-ID: 4354670 View in Reaxys 109/630 Yield

Conditions & References With (PPh3)(CO)4MnC(O)CH3 in benzene-d6, Time= 0.25h, T= 24 °C , other organic esters; other catalysts; var. reaction time; catalytic hydrosilation, Mechanism Mao, Zhibiao; Gregg, Brian T.; Cutler, Alan R.; Journal of the American Chemical Society; vol. 117; nb. 40; (1995); p. 10139 - 10140 View in Reaxys O

O OH

Rx-ID: 5319879 View in Reaxys 110/630 Yield

Conditions & References With MgyAlOx in various solvent(s), T= 299.85 °C , p= 760Torr , Condensation, dehydrogenation, Product distribution, Further Variations: Reagents, time

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Di Cosimo; Apesteguia; Gines; Iglesia; Journal of Catalysis; vol. 190; nb. 2; (2000); p. 261 - 275 View in Reaxys O

O S

Rx-ID: 26182370 View in Reaxys 111/630 Yield

Conditions & References With sulfur dioxide in water, byproducts: H2SO4; aq. or abs. ethanol, 150-200°C Pagliani, S.; Ber.; vol. 11; (1878); p. 155 View in Reaxys Pagliani, S.; Gazzetta Chimica Italiana; vol. 8; (1878); p. 101 - 104 ; (from Gmelin) View in Reaxys With sulfur dioxide in ethanol, byproducts: H2SO4; 150-200°C Pagliani, S.; Ber.; vol. 11; (1878); p. 155 View in Reaxys Pagliani, S.; Gazzetta Chimica Italiana; vol. 8; (1878); p. 101 - 104 ; (from Gmelin) View in Reaxys With SO2 in water, byproducts: H2SO4; aq. or abs. ethanol, 150-200°C vol. S: MVol.B2; 3.1.1, page 583 - 595 ; (from Gmelin) View in Reaxys With SO2 in ethanol, byproducts: H2SO4; 150-200°C vol. S: MVol.B2; 3.1.1, page 583 - 595 ; (from Gmelin) View in Reaxys Cl (v3) Cl –

(v3)

+ 2 H 2O CrOH OH 2 H 2O (v6) (v3) Cl

(v3)

Cr 2O3

Rx-ID: 26401920 View in Reaxys 112/630 Yield 63 %

Conditions & References in ethanol, byproducts: chlorethyl; react. in closed tube at 150-160 °C, 8h; Alphen, J. van; Rec. Trav. chim.; vol. 49; (1930); p. 754 - 761 ; (from Gmelin) View in Reaxys

63 %

in ethanol, byproducts: chlorethyl; react. in closed tube at 150-160 °C, 8h; vol. Cr: MVol.B; 116, page 238 - 240 ; (from Gmelin) View in Reaxys -1 F H

(v4)

(v5) (v5) H(v5) (v4) (v5) C –H

Na +

ONMo C – (v8) N

(v4)

B– F Na + F

O+ (v3)

(v5)H(v5) (v4) (v5)C H – H (v5) H H

F F

B FF

Mo+ (v4) ON C – (v8)

N+

(v3)

Rx-ID: 27602497 View in Reaxys 113/630

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Yield

Conditions & References

80 %

in acetonitrile, under N2, Mo complex dissolved in MeCN, added Et3OBF4, stirred for 0.5 h at room temp.; solvent evapd. in vac., added C6H6, filtered, solvent removed, dried invac., recrystd. from hexane with small quantity of CH2Cl2 at -50°C, elem. anal. Behrens, Helmut; Landgraf, Guenter; Merbach, Peter; Moll, Matthias; Trummer, Karl-Heinz; Journal of Organometallic Chemistry; vol. 253; nb. 2; (1983); p. 217 - 230 ; (from Gmelin) View in Reaxys O O

Rx-ID: 31417040 View in Reaxys 114/630 Yield

Conditions & References With Cp*Si(1+)* B(C6F5)4(1-) in dichloromethane-d2, Time= 144h, T= -30 °C , Inert atmosphere Leszczynska, Kinga; Mix, Andreas; Berger, Raphael J. F.; Rummel, Britta; Neumann, Beate; Stammler, HansGeorg; Jutzi, Peter; Angewandte Chemie - International Edition; vol. 50; nb. 30; (2011); p. 6843 - 6846 View in Reaxys O OH

O O

Rx-ID: 32644989 View in Reaxys 115/630 Yield

Conditions & References With aluminum oxide, Time= 8h, T= 150 °C , p= 18751.9Torr , Inert atmosphere Guilera; Bringue; Ramirez; Iborra; Tejero; Applied Catalysis A: General; vol. 413-414; (2012); p. 21 - 29 View in Reaxys

Rx-ID: 38876419 View in Reaxys 116/630 Yield

Conditions & References With water, Time= 6h, T= 500 °C , p= 760.051Torr , Flow reactor Marcos; Lucrdio; Assaf; RSC Advances; vol. 4; nb. 83; (2014); p. 43839 - 43849 View in Reaxys

Rx-ID: 39637604 View in Reaxys 117/630 Yield

Conditions & References With magnesium oxide, T= 399.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor Janssens, Wout; Makshina, Ekaterina V.; Vanelderen, Pieter; De Clippel, Filip; Houthoofd, Kristof; Kerkhofs, Stef; Martens, Johan A.; Jacobs, Pierre A.; Sels, Bert F.; ChemSusChem; vol. 8; nb. 6; (2015); p. 994 - 1008 View in Reaxys

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O N H

HN HCl

N N

Rx-ID: 41961048 View in Reaxys 118/630 Yield

Conditions & References 88 : (1R,5S)-3-{2-[(1-methyl-1H-pyrazol-4-yl)amino]pyrimidin-4-yl}-N-(propan-2-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide Example 88 (1R,5S)-3-{2-[(1-methyl-1H-pyrazol-4-yl)amino]pyrimidin-4-yl}-N-(propan-2-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide The title compound was prepared according to the method described for Example 85 using N-isopropyl-1H-imidazole-1-carboxamide (Preparation 81) and 4-((1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl)-N-(1-methyl-1H-pyrazol-4yl)pyrimidin-2-amine hydrochloride (Preparation 19). Following chromatography the residue was dissolved in DCM, precipitated by the addition of diethylether and filtered. LCMS Rt=0.61 minutes; MS m/z 371 [M+H]+ Patent; PFIZER INC.; Fensome, Andrew; Gopalsamy, Ariamala; Gerstenberger, Brian S.; Efremov, Ivan Viktorovich; Wan, Zhao-Kui; Pierce, Betsy; Telliez, Jean-Baptiste; Trujillo, John I.; Zhang, Liying; Xing, Li; (104 pag.); US2016/52930; (2016); (A1) English View in Reaxys

O S

O B2O3

Rx-ID: 26350006 View in Reaxys 119/630 Yield

Conditions & References With ethanol in ethanol, soln. of B2O3*2SO3 in ethanol Pictet; Karl; Arch. Sci. Phys. Nat.; vol. 26; nb. 4; (1908); p. 447 View in Reaxys Pictet; Karl; Bulletin de la Societe Chimique de France; vol. 3; nb. 4; (1908); p. 1121 View in Reaxys vol. B: MVol.; 12.5, page 134 - 134 ; (from Gmelin) View in Reaxys

Rx-ID: 38876418 View in Reaxys 120/630 Yield

Conditions & References With water, Time= 6h, T= 500 °C , p= 760.051Torr , Flow reactor Marcos; Lucrdio; Assaf; RSC Advances; vol. 4; nb. 83; (2014); p. 43839 - 43849 View in Reaxys

Rx-ID: 1873915 View in Reaxys 121/630 Yield

Conditions & References

21 %, 7 %, With hydrogen, ruthenium-cobalt, iodine, Time= 3h, T= 170 °C , p= 315025Torr , other promoter, other pressure, oth15 % er temperature, Product distribution

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Jenner, Gerard; Journal of Organometallic Chemistry; vol. 346; (1988); p. 237 - 252 View in Reaxys

diethylacetal

Rx-ID: 6918332 View in Reaxys 122/630 Yield

Conditions & References With hydrogen, nickel, T= 210 °C , Hydrogenation Cabanac; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 188; (1929); p. 1258 View in Reaxys

O Ti

(v4)

O2Ti

Rx-ID: 26507373 View in Reaxys 123/630 Yield

Conditions & References

10 %, 58 %, 32 %

in gas, byproducts: C2H4; decomposition at a pressure of ca. 0.01 mm of Hg at 550°C; further compound: H2 was obtained with a yield of <0.5percent; org. compounds collected in a liquid-N2 trap; NMR; GC; mass spectra Nandi, Manish; Rhubright, Doug; Sen, Ayusman; Inorganic Chemistry; vol. 29; (1990); p. 3065 - 3066 ; (from Gmelin) View in Reaxys

33 %, 38 %, 29 %

in gas, byproducts: C2H4; decomposition at a pressure of ca. 0.01 mm of Hg at 700°C; further compound: H2 was obtained with a yield of <0.5percent; org. compounds collected in a liquid-N2 trap; NMR; GC; mass spectra Nandi, Manish; Rhubright, Doug; Sen, Ayusman; Inorganic Chemistry; vol. 29; (1990); p. 3065 - 3066 ; (from Gmelin) View in Reaxys

Rx-ID: 35304537 View in Reaxys 124/630 Yield

Conditions & References With pyridine, γ-Al2O3, T= 214.84 °C , p= 760.051Torr , Inert atmosphere, Kinetics, Mechanism, Pressure DeWilde, Joseph F.; Chiang, Hsu; Hickman, Daniel A.; Ho, Christopher R.; Bhan, Aditya; ACS Catalysis; vol. 3; nb. 4; (2013); p. 798 - 807 View in Reaxys OH

Rx-ID: 41578358 View in Reaxys 125/630 Yield

Conditions & References , Time= 3h, T= 320 °C , Inert atmosphere Han, Zheng; Li, Xiang; Zhang, Minhua; Liu, Zongzhang; Gao, Meixiang; RSC Advances; vol. 5; nb. 126; (2015); p. 103982 - 103988 View in Reaxys O

Rx-ID: 637343 View in Reaxys 126/630 Yield

Conditions & References With triethylsilane, perchloric acid in acetonitrile, T= 24.9 °C , Rate constant

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Fukuzumi, Shunichi; Fujita, Morifumi; Chemistry Letters; (1991); p. 2059 - 2062 View in Reaxys With pumice stone, hydrogen, T= 90 - 170 °C Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys With fire-clay, hydrogen, T= 90 - 170 °C Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys With infusorial earht, hydrogen, T= 90 - 170 °C Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys With hydrogen, nickel, T= 90 - 170 °C Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys With hydrogen, iron, T= 90 - 170 °C Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys With hydrogen, platinum, T= 90 - 170 °C Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys With triethylsilane, perchloric acid in acetonitrile, T= 24.9 °C Fukuzumi, Shunichi; Fujita, Morifumi; Chemistry Letters; (1991); p. 2059 - 2062 View in Reaxys

O+

Rx-ID: 2430183 View in Reaxys 127/630 Yield

Conditions & References With H3[PW12O40], ethanol, T= 129.9 °C , Rate constant Lee, Kwan Young; Arai, Takeo; Nakata, Shin-Ichi; Asaoka, Sachio; Okuhara, Toshio; Misono, Makoto; Journal of the American Chemical Society; vol. 114; nb. 8; (1992); p. 2836 - 2842 View in Reaxys OH

dimethyl ether ; methylethyl ether Rx-ID: 7074547 View in Reaxys 128/630

Yield

Conditions & References With methanol, sodium alum, T= 185 °C Mailhe; de Godon; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 170; (1920); p. 329; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;27; (1920); p. 121 View in Reaxys

80/278

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-1 F (v4)

B FF

O+

Rx-ID: 29189888 View in Reaxys 129/630 Yield

Conditions & References With water D'Ulivo, Alessandro; Pagliano, Enea; Onor, Massimo; Pitzalis, Emanuela; Zamboni, Roberto; Analytical Chemistry; vol. 81; nb. 15; (2009); p. 6399 - 6406 View in Reaxys OH O

Rx-ID: 30093973 View in Reaxys 130/630 Yield

Conditions & References With aluminum oxide, oxygen, T= 250 °C Lippits; Nieuwenhuys; Journal of Catalysis; vol. 274; nb. 2; (2010); p. 142 - 149 View in Reaxys With aluminum oxide, oxygen, T= 300 °C Lippits; Nieuwenhuys; Journal of Catalysis; vol. 274; nb. 2; (2010); p. 142 - 149 View in Reaxys

Rx-ID: 41578355 View in Reaxys 131/630 Yield

Conditions & References , T= 350 °C , Inert atmosphere Han, Zheng; Li, Xiang; Zhang, Minhua; Liu, Zongzhang; Gao, Meixiang; RSC Advances; vol. 5; nb. 126; (2015); p. 103982 - 103988 View in Reaxys

Rx-ID: 41578357 View in Reaxys 132/630 Yield

S O

Rx-ID: 251178 View in Reaxys 133/630 Yield

Conditions & References With MPPA, T= -15 °C Boehme; Greve; Chemische Berichte; vol. 85; (1952); p. 409,415

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View in Reaxys O

Rx-ID: 1878331 View in Reaxys 134/630 Yield

Conditions & References

11 % Chro- With oxygen, 4-PVP-chloranil, Ambient temperature, Irradiation, PO2 : 7.0 cm Hg, PEtOH: 3.5 cm Hg, wave length-demat., 24 % pendence of the initial rate of product formation, Product distribution, Mechanism Chromat. Naito, Shuichi; Tamaru, Kenzi; Zeitschrift fuer Physikalische Chemie (Muenchen, Germany); vol. 126; (1981); p. 247 - 250 View in Reaxys With HSi-FAU zeolite, oxygen, molybdenum(VI) oxide, T= 159.85 °C , Product distribution, Further Variations: Reagents Okamoto, Yasuaki; Oshima, Nobuyuki; Kobayashi, Yasuhiro; Terasaki, Osamu; Kodaira, Tetsuya; Kubota, Takeshi; Physical Chemistry Chemical Physics; vol. 4; nb. 12; (2002); p. 2852 - 2862 View in Reaxys With oxygen, T= 179.84 °C , Kinetics, Reagent/catalyst Nair, Hari; Baertsch, Chelsey D.; Journal of Catalysis; vol. 258; nb. 1; (2008); p. 1 - 4 View in Reaxys With water, T= 249.84 °C , Flow reactor, Inert atmosphere, Catalytic behavior Riani, Paola; Garbarino, Gabriella; Lucchini, Mattia Alberto; Canepa, Fabio; Busca, Guido; Journal of Molecular Catalysis A: Chemical; vol. 383-384; (2014); p. 10 - 16 View in Reaxys

(v2)

(v3)

Rx-ID: 27086710 View in Reaxys 135/630 Yield

Conditions & References With hydrogenchloride in toluene, byproducts: C6H6, H2; argon atmosphere or vac.; 6 N HCl addn. to Zr-complex soln., org. layersepn. from aq. layer; GLC Razuvaev, G. A.; Vyshinskaya, L. I.; Vasil'eva, G. A.; Malysheva, A. V.; Rabinovich, A. M.; Journal of General Chemistry USSR (English Translation); vol. 52; (1982); p. 1178 - 1184; Zhurnal Obshchei Khimii; vol. 52; (1982); p. 1338 - 1345 ; (from Gmelin) View in Reaxys

(v2)

(v3)

Rx-ID: 27086713 View in Reaxys 136/630 Yield

Conditions & References With hydrogenchloride in toluene, byproducts: C6H6, H2; argon atmosphere or vac.; 6 N HCl addn. to Ti-complex soln., org. layersepn. from aq. layer; GLC Razuvaev, G. A.; Vyshinskaya, L. I.; Vasil'eva, G. A.; Malysheva, A. V.; Rabinovich, A. M.; Journal of General Chemistry USSR (English Translation); vol. 52; (1982); p. 1178 - 1184; Zhurnal Obshchei Khimii; vol. 52; (1982); p. 1338 - 1345 ; (from Gmelin) View in Reaxys

H2 C Ti

(v2)

C H2

Ti Cl

(v3)

Rx-ID: 27086726 View in Reaxys 137/630

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Yield

Conditions & References With hydrogenchloride in toluene, byproducts: C6H5CH3, H2; argon atmosphere or vac.; 6 N HCl addn. to Ti-complex soln., org. layersepn. from aq. layer; GLC Razuvaev, G. A.; Vyshinskaya, L. I.; Vasil'eva, G. A.; Malysheva, A. V.; Rabinovich, A. M.; Journal of General Chemistry USSR (English Translation); vol. 52; (1982); p. 1178 - 1184; Zhurnal Obshchei Khimii; vol. 52; (1982); p. 1338 - 1345 ; (from Gmelin) View in Reaxys O

Rx-ID: 40301247 View in Reaxys 138/630 Yield

Conditions & References With nitrogen, T= 149.84 °C , p= 18751.9Torr , Autoclave, Temperature, Reagent/catalyst Guilera; Ramrez; Fit; Tejero; Cunill; Catalysis Science and Technology; vol. 5; nb. 4; (2015); p. 2238 - 2250 View in Reaxys

Rx-ID: 41578354 View in Reaxys 139/630 Yield

Conditions & References , T= 350 °C , Inert atmosphere, Reagent/catalyst Han, Zheng; Li, Xiang; Zhang, Minhua; Liu, Zongzhang; Gao, Meixiang; RSC Advances; vol. 5; nb. 126; (2015); p. 103982 - 103988 View in Reaxys

Rx-ID: 41578356 View in Reaxys 140/630 Yield

Rx-ID: 42041837 View in Reaxys 141/630 Yield

Conditions & References With boron nitride, Time= 0.75h, T= 50 - 400 °C Cassinelli, Wellington H.; Martins, Leandro; Magnani, Marina; Pulcinelli, Sandra H.; Briois, Valrie; Santilli, Celso V.; RSC Advances; vol. 6; nb. 25; (2016); p. 20453 - 20457 View in Reaxys

Br–+Mg

Rx-ID: 59499 View in Reaxys 142/630

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Yield

Conditions & References With AgBr Joseph; Gardner; Journal of Organic Chemistry; vol. 5; (1940); p. 60,64 View in Reaxys Bickley; Gardner; Journal of Organic Chemistry; vol. 5; (1940); p. 126,130, 131 View in Reaxys Br

Rx-ID: 93228 View in Reaxys 143/630 Yield

Conditions & References With mercury(II) oxide, schon bei laengerer Bestrahlung mit Sonnenlicht Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 411 View in Reaxys With water Frankland; Justus Liebigs Annalen der Chemie; vol. 71; (1849); p. 203; Justus Liebigs Annalen der Chemie; vol. 85; (1853); p. 360 View in Reaxys Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 411 View in Reaxys Nef; Justus Liebigs Annalen der Chemie; vol. 298; (1897); p. 322; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 50 View in Reaxys

O O

Rx-ID: 799327 View in Reaxys 144/630 Yield

Conditions & References anschliessend Behandeln mit wss.HCl und Erhitzen der wss.Reaktionsloesung Haller; Schaffer; Journal of the American Chemical Society; vol. 61; (1939); p. 2175 View in Reaxys -1 -1

(v4)

B FF

(v4)

O O+

B FF

O+ O

Rx-ID: 1522451 View in Reaxys 145/630 Yield

Conditions & References in dichloromethane-d2, T= 25 °C , Equilibrium constant, Rate constant Wiberg, Kenneth B.; Waldron, Boy F.; Journal of the American Chemical Society; vol. 113; nb. 20; (1991); p. 7705 - 7709 View in Reaxys

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-1

(v4)

B F FF

(v4)

O+

B FF

O C+ O

Rx-ID: 1536118 View in Reaxys 146/630 Yield

-1

(v4)

CH 2

B FF

O C H2

O+

B FF

C+ O O

Rx-ID: 1706506 View in Reaxys 147/630 Yield

Conditions & References in dichloromethane-d2, T= 25 °C , Equilibrium constant Wiberg, Kenneth B.; Waldron, Boy F.; Journal of the American Chemical Society; vol. 113; nb. 20; (1991); p. 7705 - 7709 View in Reaxys

N+

I–

O–

O N+

S OO

Rx-ID: 2429633 View in Reaxys 148/630 Yield

Conditions & References

87 %

With diethyl sulphate, Time= 0.5h, T= 100 °C , Product distribution Vompe, A. F.; Meshki, L. M.; Journal of Organic Chemistry USSR (English Translation); vol. 17; (1981); p. 1551 1554; Zhurnal Organicheskoi Khimii; vol. 17; nb. 8; (1981); p. 1735 - 1739 View in Reaxys

87 %

With diethyl sulphate, Time= 0.5h, T= 100 °C Vompe, A. F.; Meshki, L. M.; Journal of Organic Chemistry USSR (English Translation); vol. 17; (1981); p. 1551 1554; Zhurnal Organicheskoi Khimii; vol. 17; nb. 8; (1981); p. 1735 - 1739 View in Reaxys -1

-1

F (v4)

B FF

(v4)

O+

B FF

C+

Rx-ID: 2899228 View in Reaxys 149/630 Yield

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View in Reaxys -1

-1

(v4)

B FF

O O

O+

B FF

O+

Rx-ID: 3876681 View in Reaxys 150/630 Yield

N–

O 6Li+

racemate

6Li+

racemate

Rx-ID: 4726887 View in Reaxys 151/630 Yield

Conditions & References in toluene, pentane, T= -80 °C , Equilibrium constant Remenar, Julius F.; Lucht, Brett L.; Collum, David B.; Journal of the American Chemical Society; vol. 119; nb. 24; (1997); p. 5567 - 5572 View in Reaxys

Rx-ID: 28781265 View in Reaxys 152/630 Yield

Conditions & References

> 95 %Spectr.

With [Cp*IrCl2(C(NBuCHCHNBu))], silver trifluoromethanesulfonate, Time= 12h, T= 110 °C Prades, Amparo; Corberan, Rosa; Poyatos, Macarena; Peris, Eduardo; Chemistry - A European Journal; vol. 14; nb. 36; (2008); p. 11474 - 11479 View in Reaxys

Rx-ID: 31642768 View in Reaxys 153/630 Yield

Conditions & References With cesium hydroxide monohydrate, tungsten hexachloride, Time= 20h, T= 140 - 240 °C , Autoclave Guo, Chongshen; Yin, Shu; Yan, Mei; Sato, Tsugio; Journal of Materials Chemistry; vol. 21; nb. 13; (2011); p. 5099 - 5105 View in Reaxys

Rx-ID: 33153008 View in Reaxys 154/630 Yield

Conditions & References With zeolite beta CP 814 C catalyst (Si/Al2 38, Zeolyst), T= 149.84 °C

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Radhakrishnan, Sambhu; Franken, Joris; Martens, Johan A.; Green Chemistry; vol. 14; nb. 5; (2012); p. 1475 1479 View in Reaxys O

Rx-ID: 3916819 View in Reaxys 155/630 Yield

Conditions & References With hydrogen, iron RFC, T= 280 - 300 °C , p= 15001.2 - 22501.8Torr , Product distribution, Mechanism Kliger, G. A.; Lesik, O. A.; Marchevskaya, E. V.; Mikaya, A. I.; Zaikin, V. G.; et al.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 23; nb. 2; (1987); p. 161 - 164; Khimiya Geterotsiklicheskikh Soedinenii; vol. 23; nb. 2; (1987); p. 195 - 198 View in Reaxys

O O

Rx-ID: 4671015 View in Reaxys 156/630 Yield

Conditions & References

2.01 mmol, With 4 A molecular sieve, sodium ethanolate, (3-cumenyl-5-Me-pyrazolyl)3-borate-Zn-OH, Time= 20h, T= 150 °C , 0.05 mmol, p= 75006Torr , var. of catalyst, reagent, pressure, temp., time, without NaOEt, Product distribution 0.98 mmol Ruf, Michael; Schell, Friedrich Alexander; Walz, Rainer; Vahrenkamp, Heinrich; Chemische Berichte; vol. 130; nb. 1; (1997); p. 101 - 104 View in Reaxys O O

Rx-ID: 4922346 View in Reaxys 157/630 Yield

Conditions & References

95 % Chromat.

With sodium in various solvent(s), Time= 8h, T= 254 °C , Product distribution Yu, Zhengkun; Verkade, John G.; Tetrahedron Letters; vol. 39; nb. 18; (1998); p. 2671 - 2674 View in Reaxys

Rx-ID: 5278676 View in Reaxys 158/630 Yield

Conditions & References With hydrogen, rhenium, sibunite, Time= 5h, T= 230 °C , p= 22501.8Torr , Catalytic hydrogenation, Product distribution, Further Variations: Catalysts, Temperatures Ryashentseva; Avaev; Russian Chemical Bulletin; vol. 48; nb. 5; (1999); p. 998 - 1000 View in Reaxys N

N O

CO2 Rx-ID: 5728214 View in Reaxys 159/630

Yield

Conditions & References With air, zeolite H-Nu-10, ammonia, Time= 18h, T= 350 °C , Further byproducts given Le Febre; Hoefnagel; Van Bekkum; Recueil des Travaux Chimiques des Pays-Bas-Journal of the Royal Netherlands; vol. 115; nb. 11-12; (1996); p. 511 - 518 View in Reaxys

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CO2

Rx-ID: 5728215 View in Reaxys 160/630 Yield

aluminium oxide

Rx-ID: 6945961 View in Reaxys 161/630 Yield

Conditions & References T= 250 - 350 °C Clark; Graham; Winter; Journal of the American Chemical Society; vol. 47; (1925); p. 2753 View in Reaxys Pease; Yung; Journal of the American Chemical Society; vol. 46; (1924); p. 395 View in Reaxys Alvorado; Journal of the American Chemical Society; vol. 50; (1928); p. 790 View in Reaxys Senderens; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 35; (1924); p. 1144 View in Reaxys

(v5) (v5) (v5) (v5)

(v5) (v5) (v5)

(v3)

Yb O

(v11)

N (v5)

(v5) (v5) (v5)(v5)

(v5)

Yb S

(v11) N

(v5) (v5) (v5)

Rx-ID: 26367984 View in Reaxys 162/630 Yield

Conditions & References in pentane, stirring, 2 h, under N2; filtn., concn., cooling to -10°C; IR Berg, David J.; Andersen, Richard A.; Zalkin, Allan; Organometallics; vol. 7; (1988); p. 1858 - 1863 ; (from Gmelin) View in Reaxys

Rx-ID: 29107656 View in Reaxys 163/630 Yield

Conditions & References With Amberlyst 15, Time= 1h, T= 60 °C Kovalchuk; Kochkin; Sfihi; Zaitsev; Fraissard; Journal of Catalysis; vol. 263; nb. 2; (2009); p. 247 - 257 View in Reaxys

OH OH

O OH

HO HO

Rx-ID: 29315733 View in Reaxys 164/630 Yield

Conditions & References With Amberlyst A-15 resin, Time= 6h, T= 159.84 °C Pariente, Stephane; Tanchoux, Nathalie; Fajula, Franois; Green Chemistry; vol. 11; nb. 8; (2009); p. 1256 - 1261 View in Reaxys

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2016-05-04 01:50:52

Rx-ID: 33153009 View in Reaxys 165/630 Yield

Conditions & References With water, T= 149.84 °C Radhakrishnan, Sambhu; Franken, Joris; Martens, Johan A.; Green Chemistry; vol. 14; nb. 5; (2012); p. 1475 1479 View in Reaxys

Rx-ID: 33153010 View in Reaxys 166/630 Yield

Conditions & References With zeolite beta CP 814 C catalyst (Si/Al2 38, Zeolyst), T= 149.84 °C Radhakrishnan, Sambhu; Franken, Joris; Martens, Johan A.; Green Chemistry; vol. 14; nb. 5; (2012); p. 1475 1479 View in Reaxys

O O

Rx-ID: 33153011 View in Reaxys 167/630 Yield

Rx-ID: 39637605 View in Reaxys 168/630 Yield

Conditions & References With 0Ag/MgO-SiO2, T= 399.84 °C , p= 760.051Torr , Inert atmosphere, Flow reactor Janssens, Wout; Makshina, Ekaterina V.; Vanelderen, Pieter; De Clippel, Filip; Houthoofd, Kristof; Kerkhofs, Stef; Martens, Johan A.; Jacobs, Pierre A.; Sels, Bert F.; ChemSusChem; vol. 8; nb. 6; (2015); p. 994 - 1008 View in Reaxys With Zr-containing molecular sieve (Si/Zr = 200) doped with silver, Time= 3h, T= 319.84 °C , Gas phase, Reagent/ catalyst Sushkevich, Vitaly L.; Ivanova, Irina I.; Taarning, Esben; Green Chemistry; vol. 17; nb. 4; (2015); p. 2552 - 2559 View in Reaxys Stage 1: With Cu/SiO2, Gas phase Stage 2:Catalytic behavior, Reagent/catalyst Klein, Alexander; Keisers, Kristina; Palkovits, Regina; Applied Catalysis A: General; vol. 514; (2016); p. 192 202 View in Reaxys

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Rx-ID: 92757 View in Reaxys 169/630 Yield

Conditions & References T= 200 °C Reynoso; Annales de Chimie (Cachan, France); vol. &lt;3&gt; 48; (1856); p. 411 View in Reaxys Geschwindigkeit v.Halban; Gast; Zeitschrift fuer Physikalische Chemie, Stoechiometrie und Verwandtschaftslehre; vol. 91; (1916); p. 598 View in Reaxys O– Na +

I O

Rx-ID: 631715 View in Reaxys 170/630 Yield

Conditions & References With ethanol, Geschwindigkeit Marshall; Acree; Journal of Physical Chemistry; vol. 19; (1915); p. 596 View in Reaxys With ethanol Bishop; Journal of the Society of Chemical Industry, London; vol. 43; (1924); p. 23 T; Chem. Zentralbl.; vol. 95; nb. I; (1924); p. 2678 View in Reaxys NH

H 2N

N H

Rx-ID: 718837 View in Reaxys 171/630 Yield

Conditions & References With disulfur dichloride Ishikawa; Scientific Papers of the Institute of Physical and Chemical Research (Japan); vol. 7; p. 242; Chem. Zentralbl.; vol. 99; nb. I; (1928); p. 1763 View in Reaxys Ishikawa; Scientific Papers of the Institute of Physical and Chemical Research (Japan); vol. 3; p. 150; Chem. Zentralbl.; vol. 96; nb. II; (1925); p. 2206 View in Reaxys With sulfuryl dichloride Ishikawa; Scientific Papers of the Institute of Physical and Chemical Research (Japan); vol. 7; p. 242; Chem. Zentralbl.; vol. 99; nb. I; (1928); p. 1763 View in Reaxys Ishikawa; Scientific Papers of the Institute of Physical and Chemical Research (Japan); vol. 3; p. 150; Chem. Zentralbl.; vol. 96; nb. II; (1925); p. 2206 View in Reaxys

Rx-ID: 1895933 View in Reaxys 172/630 Yield

Conditions & References With water, proton-exchanged ferrierite-type zeolite, T= 199.9 °C , p= 760Torr , various proton-exchanged zeolites, Product distribution

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Iwamoto, Masakazu; Tajima, Masahiro; Kagawa, Shuichi; Journal of the Chemical Society, Chemical Communications; nb. 4; (1985); p. 228 - 230 View in Reaxys O C

O O

Rx-ID: 3347851 View in Reaxys 173/630 Yield

Conditions & References

135.2 mmol, 4.5 mmol, 3.3 mmol, 55.0 mmol, 22.1 mmol, 29.3 mmol

With Rhodium trichloride, hydrogen, methyl iodide, dicarbonyldiiodorhodate(I) anion, T= 170 °C , p= 60004.8Torr , var. temp.; H2/CO ratio and catalysts (chlorocarbonylrhodium; carbonylrhodium), Product distribution, Mechanism Raspolli Galletti, A.M.; Braca, G.; Sbrana, G.; Journal of Organometallic Chemistry; vol. 356; (1988); p. 221 - 232 View in Reaxys

Rx-ID: 4865275 View in Reaxys 174/630 Yield

Conditions & References With air, molecular sieve, T= 249.9 °C , mechanism, Eapp, var. temp, pressure of EtOH, and catalyst pretreatment, Product distribution, Kinetics, Rate constant Kannan; Sen; Sivasanker; Journal of Catalysis; vol. 170; nb. 2; (1997); p. 304 - 310 View in Reaxys OH

MgCl2

Rx-ID: 6672795 View in Reaxys 175/630 Yield

Conditions & References T= 370 °C , p= 220652Torr Ipatieff; Monroe; Journal of the American Chemical Society; vol. 66; (1944); p. 1630 View in Reaxys OH

alkylenene Rx-ID: 7068652 View in Reaxys 176/630

Yield

Conditions & References With sulfuric acid Berthelot; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1867); p. 350; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1869); p. 330 View in Reaxys Serullas; Annales de Chimie (Cachan, France); vol. &lt;2&gt;39; (1828); p. 152; ; vol. 9; p. 252 View in Reaxys

silver salt of β-naphthylnitramine

Rx-ID: 8130508 View in Reaxys 177/630

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2016-05-04 01:50:52

Yield

Conditions & References With methyl iodide Bamberger; Dietrich; Chemische Berichte; vol. 30; (1897); p. 1252,1254 View in Reaxys Boecking; View in Reaxys

H P

ClCu

Cl 2Cu

Cl 2Cu( 1-)

O P

Rx-ID: 26100377 View in Reaxys 178/630 Yield

Conditions & References With ethanol in acetonitrile, Kinetics, continnous-flow apparatus, passge of PH3/Ar mixt.; gas chrommatographie anal. Dorfman, Ya. A.; Levina, L. V.; Petrova, T. V.; Emel'yanova, V. S.; Polimbetova, G. S.; Journal of General Chemistry USSR (English Translation); vol. 59; (1989); p. 1292 - 1293; Zhurnal Obshchei Khimii; vol. 59; (1989); p. 1454 1455 ; (from Gmelin) View in Reaxys

3 Al3+

2 Br– 1.5 O

H H H

O–

Rx-ID: 26173508 View in Reaxys 179/630 Yield

Conditions & References With air, standing on wet air decomposes Funk, H.; Schormueller, J.; Z. Anorg. Chem.; vol. 199; (1931); p. 96 ; (from Gmelin) View in Reaxys With air, standing on wet air decomposes vol. Al: MVol.B1; 7.5.3.3, page 300 - 301 ; (from Gmelin) View in Reaxys

3 Al3+

Br–

H 8 H H

O–

Rx-ID: 26173795 View in Reaxys 180/630 Yield

Conditions & References With air, on moist air decomposes, firstly ether, next acetic acid formed Funk, H.; Schormueller, J.; Z. Anorg. Chem.; vol. 199; (1931); p. 95 ; (from Gmelin) View in Reaxys With air, on moist air decomposes, firstly ether, next acetic acid formed vol. Al: MVol.B1; 7.5.3.3, page 300 - 301 ; (from Gmelin) View in Reaxys

(v5)(v5) (v5) (v5) (v5)

Yb (v3) (v12) Cl O

(v5)

(v5) (v5)(v5) (v5)

(v5)

Yb Cl

(v3)

(v7)Cl

(v5)

Rx-ID: 26490783 View in Reaxys 181/630

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Yield

Conditions & References in benzene-d6, under N2, 23°C, color change purple-blue, light blue, 1 h; not isolated, detected by (1)H-NMR Finke, R. G.; Keenan, S. R.; Watson, P. L.; Organometallics; vol. 8; (1989); p. 263 - 277 ; (from Gmelin) View in Reaxys in toluene, Kinetics, under N2, 22°C; not isolated, detected by UV/VIS Finke, R. G.; Keenan, S. R.; Watson, P. L.; Organometallics; vol. 8; (1989); p. 263 - 277 ; (from Gmelin) View in Reaxys 2 Cl –

(v2)

H O

Rx-ID: 26649592 View in Reaxys 182/630 Yield

Conditions & References in neat (no solvent), decomposition on heating; Prandl, W.; Hess, L.; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 82; (1913); p. 103 - 129 ; (from Gmelin) View in Reaxys in neat (no solvent), decomposition on heating; vol. V: MVol.B2; 177, page 744 - 746 ; (from Gmelin) View in Reaxys

O I2Mg

Rx-ID: 628943 View in Reaxys 183/630 Yield

Conditions & References T= 190 °C Menschutkin,B.; ; vol. 52; (1907); p. 15 View in Reaxys Menschutkin,B.; Chem. Zentralbl.; vol. 77; nb. I; (1906); p. 335,742 View in Reaxys T= 10 °C , Geschwindigkeit im Hochvakuum Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys T= 100 °C , p= 40 - 60Torr , Geschwindigkeit Meisenheimer; Casper; Chemische Berichte; vol. 54; (1921); p. 1663 View in Reaxys

SiH

Si O

Rx-ID: 1228385 View in Reaxys 184/630 Yield

Conditions & References With triethylsilane, nickel dichloride Bourhis,R.; Frainnet,E.; Journal of Organometallic Chemistry; vol. 86; (1975); p. 205 - 218 View in Reaxys

93/278

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O P

Rx-ID: 1878296 View in Reaxys 185/630 Yield

Conditions & References With anhydrous phosphine, copper dichloride in N,N-dimethyl-formamide, T= 59.9 °C Dorfman, Ya. A.; Levina, L. V.; Petrova, T. V.; Emel'yanova, V. S.; Polimbetova, G. S.; J. Gen. Chem. USSR (Engl. Transl.); vol. 60; nb. 4.1; (1990); p. 837 - 840,736 - 742 View in Reaxys With anhydrous phosphine, iron(III) chloride in N,N-dimethyl-formamide, T= 19.9 °C , ΔS(excit); reaction also with CuCl2, Rate constant, Thermodynamic data Dorfman, Ya. A.; Levina, L. V.; Petrova, T. V.; Emel'yanova, V. S.; Polimbetova, G. S.; J. Gen. Chem. USSR (Engl. Transl.); vol. 60; nb. 4.1; (1990); p. 837 - 840,736 - 742 View in Reaxys O

Rx-ID: 1878346 View in Reaxys 186/630 Yield

Conditions & References

19.5 %, 41.4 %

With air, aluminium trifluoride, gold, Time= 0.0227778h, T= 299.9 °C , various catalyst, temperature, Product distribution Kazakova, G. D.; Komolova, L. F.; Nefedov, B. K.; Mardashev, Yu. S.; Russian Journal of Physical Chemistry; vol. 57; nb. 1; (1983); p. 131 - 132; Zhurnal Fizicheskoi Khimii; vol. 57; nb. 1; (1983); p. 221 - 223 View in Reaxys O

Rx-ID: 1878348 View in Reaxys 187/630 Yield

Conditions & References With oxygen, MoO3 upon silica gel, T= 179.9 °C , var. Mo conc. of cat., Product distribution, Rate constant Ono, Takehido; Anpo, Masakazu; Kubokawa, Yutaka; Journal of Physical Chemistry; vol. 90; nb. 20; (1986); p. 4780 - 4784 View in Reaxys

92 % Chromat., 2 % Chromat., 5 % Chromat.

With tetrachloromethane, bis(acetylacetonate)oxovanadium, Time= 1h, T= 150 °C Khusnutdinov; Shchadneva; Baiguzina; Lavrentieva; Dzhemilev; Russian Chemical Bulletin; vol. 51; nb. 11; (2002); p. 2074 - 2079 View in Reaxys

H N

N O

Rx-ID: 3916818 View in Reaxys 188/630 Yield 29 %

Conditions & References With ammonia, hydrogen, iron RFC, T= 260 °C , other temp. (250, 255, 280, 290 deg C), Product distribution, Mechanism Kliger, G. A.; Lesik, O. A.; Marchevskaya, E. V.; Mikaya, A. I.; Zaikin, V. G.; et al.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 23; nb. 2; (1987); p. 161 - 164; Khimiya Geterotsiklicheskikh Soedinenii; vol. 23; nb. 2; (1987); p. 195 - 198 View in Reaxys

94/278

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ZnCl2

Rx-ID: 6672021 View in Reaxys 189/630 Yield

Conditions & References T= 150 - 170 °C Kyrides; Journal of the American Chemical Society; vol. 55; (1933); p. 1209,1211 View in Reaxys

Cl Fe Cl

(v3)

Rx-ID: 6672794 View in Reaxys 190/630 Yield

Conditions & References T= 370 °C , p= 220652Torr Ipatieff; Monroe; Journal of the American Chemical Society; vol. 66; (1944); p. 1630 View in Reaxys

CO2 Rx-ID: 7072210 View in Reaxys 191/630

Yield

Conditions & References With water, oxygen, silica gel, molybdenum(VI) oxide in gas, T= 289.9 °C , other temp., other catalysts, Product distribution Zhang, Weimin; Desikan Anantha; Oyama, S. Ted; Journal of Physical Chemistry; vol. 99; nb. 39; (1995); p. 14468 - 14476 View in Reaxys OH

diethanesulfonate Rx-ID: 7073983 View in Reaxys 192/630

Yield

Conditions & References With sulfuric acid Claesson; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 19; (1879); p. 259 View in Reaxys OH

ethanesulfonic acid , isaethionic acid (?) Rx-ID: 7075524 View in Reaxys 193/630

Yield

Conditions & References With sulfuric acid Prunier; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 124; (1897); p. 1028 View in Reaxys OH

ethylene, sulfur dioxide Rx-ID: 7075715 View in Reaxys 194/630

Yield

Conditions & References With sulfuric acid Klar; ; I. 21, 299 View in Reaxys

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H2O

Rx-ID: 7076559 View in Reaxys 195/630 Yield

Conditions & References With calcined aluminium hydroxide in gas, T= 250 °C , influence of water, Kinetics, Rate constant Moravek, Vladimir; Kraus, Milos; Collection of Czechoslovak Chemical Communications; vol. 51; nb. 4; (1986); p. 763 - 773 View in Reaxys

O2Si

Si O

Rx-ID: 26174181 View in Reaxys 196/630 Yield

Conditions & References With aluminium trichloride, decompn. of Si(OC2H5)4 with AlCl3; Stokes, H. N.; American Chemical Journal; vol. 14; (1892); p. 438 - 454 ; (from Gmelin) View in Reaxys With AlCl3, decompn. of Si(OC2H5)4 with AlCl3; vol. Si: MVol.C; 120, page 335 - 337 ; (from Gmelin) View in Reaxys Cl

Si Si

Si N

Si Al

P P

Si N Si

Rx-ID: 26408679 View in Reaxys 197/630 Yield

Conditions & References in hexane, combining (Me3Si)3Al.Et2O-soln. with Ph2PN(SiMe3)2-soln. at -78 °C, warming to 25 °C and stirring for 4 h ; under inert gas; evapn., (31P)-NMR, IR and MS Janik, Jerzy F.; Duesler, Eileen N.; McNamara, William F.; Westerhausen, Matthius; Paine, Robert T.; Organometallics; vol. 8; (1989); p. 506 - 514 ; (from Gmelin) View in Reaxys Cl

Cl Si

O2Si

Rx-ID: 26454129 View in Reaxys 198/630 Yield

Conditions & References With aluminium trichloride, on heating; Stokes, H. N.; American Chemical Journal; vol. 14; (1892); p. 438 - 454 ; (from Gmelin) View in Reaxys With AlCl3, on heating; vol. Si: MVol.C; 137, page 379 - 380 ; (from Gmelin) View in Reaxys

96/278

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Si O

O2Si

Rx-ID: 26454184 View in Reaxys 199/630 Yield

Conditions & References With aluminium trichloride Stokes, H. N.; American Chemical Journal; vol. 14; (1892); p. 438 - 454 ; (from Gmelin) View in Reaxys With AlCl3 vol. Si: MVol.C; 136, page 377 - 379 ; (from Gmelin) View in Reaxys Cl Si Si

Al Si

Si Al

Rx-ID: 26493720 View in Reaxys 200/630 Yield

Conditions & References in toluene, combining (Me3Si)3Al.Et2O-soln. with Ph2PCl-soln. at -78 °C, stirring and warming to 25 °C overnight ; under inert gas; evapn., (31P)-NMR, IR and MS Janik, Jerzy F.; Duesler, Eileen N.; McNamara, William F.; Westerhausen, Matthius; Paine, Robert T.; Organometallics; vol. 8; (1989); p. 506 - 514 ; (from Gmelin) View in Reaxys

(v5)(v5) (v5)

(v5) (v5)(v5) (v5)

(v5) (v5) (v5) (v5)

Cl Cl Yb

Yb (v3) (v12) Cl O

(v7)Cl

(v3)

(v4)

(v5)

Rx-ID: 26625532 View in Reaxys 201/630 Yield

Conditions & References in benzene-d6, Kinetics, color change purple-blue, light blue (1 h) Finke, R. G.; Keenan, S. R.; Watson, P. L.; Organometallics; vol. 8; (1989); p. 263 - 277 ; (from Gmelin) View in Reaxys

OH OH

OH O

O OH

HO HO

Rx-ID: 29315732 View in Reaxys 202/630 Yield

Conditions & References With Amberlyst A-35 resin, Time= 6h, T= 159.84 °C Pariente, Stephane; Tanchoux, Nathalie; Fajula, Franois; Green Chemistry; vol. 11; nb. 8; (2009); p. 1256 - 1261

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View in Reaxys O

Rx-ID: 41478226 View in Reaxys 203/630 Yield

Conditions & References

70 %Spectr.

With [{κ3-N,Si,C-PhB(4,4-dimethyl-2-oxazoline)((4,4-dimethyl-2-oxazoline)SiHPh)(1-mesitylimidazole)}Rh(H)CO] [HB(C6F5)3], phenylsilane in chloroform-d1, Time= 0.5h, T= 25 °C , Inert atmosphere, Schlenk technique, Glovebox, Catalytic behavior, Solvent, Concentration Xu, Songchen; Boschen, Jeffery S.; Biswas, Abhranil; Kobayashi, Takeshi; Pruski, Marek; Windus, Theresa L.; Sadow, Aaron D.; Dalton Transactions; vol. 44; nb. 36; (2015); p. 15897 - 15904 View in Reaxys O– Na +

Rx-ID: 93176 View in Reaxys 204/630 Yield

Conditions & References With ethanol, Geschwindigkeit Marshall; Acree; Journal of Physical Chemistry; vol. 19; (1915); p. 596 View in Reaxys

Rx-ID: 193870 View in Reaxys 205/630 Yield

Conditions & References With sulfuric acid, Npr2: Diamylen; Npr3: Aethylamylketone; Npr4: Methylhexylketon Hartwig; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;23; (1881); p. 449 View in Reaxys

S N

Rx-ID: 364464 View in Reaxys 206/630 Yield

Conditions & References With hydrogen sulfide Lecher; Chemische Berichte; vol. 58; (1925); p. 415 View in Reaxys

H N

H N O

O O

Rx-ID: 512397 View in Reaxys 207/630 Yield

Conditions & References With hydrogenchloride, ethanol Curtius; Sauerberg; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 125; (1930); p. 139,146 View in Reaxys

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S S

Rx-ID: 795456 View in Reaxys 208/630 Yield

Conditions & References With hydrogen sulfide Lecher; Chemische Berichte; vol. 58; (1925); p. 415 View in Reaxys

O C+

9-methyl-xanthydrol

Cl –

2 H

Rx-ID: 8236775 View in Reaxys 209/630 Yield

Conditions & References With hydrogenchloride Atkinson; Heilbron; Journal of the Chemical Society; (1926); p. 682 View in Reaxys

(v5) (v5) (v5) (v5)

(v3)

Yb O

(v11)

(v5) (v5) (v5)(v5)

(v5)(v5) (v5)

(v5) (v5)(v5) (v5)

(v5) (v5) (v5)

Yb (v3) (v12) Cl O

(v5)

(v7)Cl

(v5)

Rx-ID: 26367977 View in Reaxys 210/630 Yield

Conditions & References in benzene-d6, under N2, 23°C, color change green-purple-blue; not isolated, detected by (1)H-NMR Finke, R. G.; Keenan, S. R.; Watson, P. L.; Organometallics; vol. 8; (1989); p. 263 - 277 ; (from Gmelin) View in Reaxys

(v5) (v5) (v5) (v5)

(v3)

Yb O

(v11)

(v5) (v5) (v5)(v5)

(v5) (v5)

(v5)(v5) (v5)

(v5) (v5)

Yb F F

(v5)

(v7)

(v5) (v5)

Yb (v3) (v12) F O

(v5)

Rx-ID: 26552363 View in Reaxys 211/630 Yield

Conditions & References in benzene-d6, under N2, 23°C; not isolated, detected by (1)H-NMR

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Finke, R. G.; Keenan, S. R.; Watson, P. L.; Organometallics; vol. 8; (1989); p. 263 - 277 ; (from Gmelin) View in Reaxys

(v5) (v5) (v5) (v5)

(v3)

Yb O

(v11)

(v5) (v5) (v5)(v5)

(v5) (v5) (v5) (v5)

Br Yb (v12) O

(v5) (v5)

(v5) (v3) (v5) (v5) (v5)

(v5) (v5)

Yb Br Br

(v7)

Rx-ID: 26552364 View in Reaxys 212/630 Yield

Conditions & References in benzene-d6, under N2, 23°C; not isolated, detected by (1)H-NMR Finke, R. G.; Keenan, S. R.; Watson, P. L.; Organometallics; vol. 8; (1989); p. 263 - 277 ; (from Gmelin) View in Reaxys -1

-1

I (v4)

Bi I I

O+

Bi I (v4) I

Rx-ID: 26636936 View in Reaxys 213/630 Yield

Conditions & References in neat (no solvent), decomposition; Meerwein, H.; Battenberg, E.; Gold, H.; Pfeil, E.; Wilfang, G.; J. prakt. Chem. (2); vol. 154; (1939); p. 83 - 156 View in Reaxys vol. Bi: SVol.; 184, page 721 - 722 ; (from Gmelin) View in Reaxys

F HLi

B– HH

Li+

Rx-ID: 26677187 View in Reaxys 214/630 Yield

Conditions & References in diethyl ether, byproducts: LiF; heating at 120-130°C several h, cooling, dissolving in ether, decanting, solvent evapn.; recrystn. from anhydrous ether vol. B: B-Verb.8; 1.2, page 2 - 5 View in Reaxys Becher, H. J.; in: G. Brauer, Handbuch der Praeparativen Anorganischen Chemie, 2. Edn., Vol. 1, Ferdinand Enke, Stuttgart 1960, pp.689/91 ; (from Gmelin) View in Reaxys

Rx-ID: 40295688 View in Reaxys 215/630 Yield 36.7 %, 1.9 %, 0.1 %, 6.4 %, 5.0 %, 2.4 %

Conditions & References With deficient carbonate-containing hydroxyapatites (HapD), T= 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 62.1 percent

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Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys 2.6 %, 0.8 %, 0.2 %, 15.1 %, 1.6 %, 1.4 %

0.4 %, 0.8 %, 0.1 %, 7.1 %, 0.7 %, 0.2 %

0.1 %, 1.8 %, 0.1 %, 6.5 %, 0.6 %, 0.2 %

0.1 %, 0.3 %, 0.2 %, 4.2 %, 0.04 %, 0.04 %

0.02 %, 0.5 %, 0.4 %, 3.7 %, 0.03 %, 0.02 %

With deficient carbonate-containing hydroxyapatites (HapD), T= 350 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 27 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With deficient carbonate-containing hydroxyapatites (HapD), T= 300 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 14.2 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With stoichiometric carbonate-containing hydroxyapatites (Hap), T= 300 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 13 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With carbonated carbonate-containing hydroxyapatites (Hap-CO3), T= 300 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 5.8 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With carbonated carbonate-containing hydroxyapatites (HapNa-CO3), T= 300 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 5.4 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys

Rx-ID: 57376 View in Reaxys 216/630 Yield

Conditions & References With sulfuric acid Norton; Prescott; American Chemical Journal; vol. 6; (1884); p. 243 View in Reaxys

O O

BrClMg

Rx-ID: 537351 View in Reaxys 217/630 Yield

Conditions & References im Hochvakuum Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343

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View in Reaxys T= 10 °C , p= 15Torr , Geschwindigkeit Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys T= 10 °C , Geschwindigkeit im Hochvakuum Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys

O O

Rx-ID: 846446 View in Reaxys 218/630 Yield

Conditions & References With N,N-diethylaniline Patent; Shell Devel. Co.; US2895982; (1956) View in Reaxys

SiH

O Si

Rx-ID: 908037 View in Reaxys 219/630 Yield

Conditions & References With zinc(II) chloride, Time= 25h, Heating Frainnet,E.; Esclamadon,C.; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 254; (1962); p. 1814 - 1816 View in Reaxys O

O+ H

OH +

Rx-ID: 1551946 View in Reaxys 220/630 Yield

Conditions & References T= 24.9 °C , ΔG0, Thermodynamic data Bromilow, J.; Abboud, J. L. M.; Lebrilla, C. B.; Taft, R. W.; Scorrano, G.; Lucchini V.; Journal of the American Chemical Society; vol. 103; nb. 18; (1981); p. 5448 - 5453 View in Reaxys O

N O

O+ H

N OH +

Rx-ID: 1552060 View in Reaxys 221/630 Yield

Rx-ID: 1670663 View in Reaxys 222/630

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Yield

Conditions & References With potassium hydroxide in ethanol, water, T= 100 °C , other temp., other solvent, other reag., Kinetics, Product distribution Flint, A.; Jansen, W.; Journal fuer Praktische Chemie (Leipzig); vol. 331; nb. 5; (1989); p. 709 - 720 View in Reaxys -1 F

-1 (v4)

B FF

(v4)

O+

B FF

N+

Rx-ID: 1855625 View in Reaxys 223/630 Yield

Conditions & References Time= 3h, T= 15 °C Kresze, Guenter; Roessert, Michael; Liebigs Annalen der Chemie; nb. 1; (1981); p. 58 - 64 View in Reaxys -1

-1

(v4)

B FF

O+

B FF

N+

Rx-ID: 1859336 View in Reaxys 224/630 Yield

Conditions & References Time= 3h, T= 15 °C Kresze, Guenter; Roessert, Michael; Liebigs Annalen der Chemie; nb. 1; (1981); p. 58 - 64 View in Reaxys OH O

Rx-ID: 1878290 View in Reaxys 225/630 Yield

Conditions & References With aluminum oxide, T= 26.9 - 626.9 °C , other alcohols; also with Ni/Al2O3 catalyst; var. temp. range, Product distribution Chen, Baoshu; Falconer, John L.; Journal of Catalysis; vol. 144; nb. 1; (1993); p. 214 - 226 View in Reaxys

O+ H

Rx-ID: 1906350 View in Reaxys 226/630 Yield

O+ H

Rx-ID: 1906357 View in Reaxys 227/630 Yield

Conditions & References T= 24.9 °C , ΔG0, Thermodynamic data

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Bromilow, J.; Abboud, J. L. M.; Lebrilla, C. B.; Taft, R. W.; Scorrano, G.; Lucchini V.; Journal of the American Chemical Society; vol. 103; nb. 18; (1981); p. 5448 - 5453 View in Reaxys

H 2N

Rx-ID: 1971080 View in Reaxys 228/630 Yield

Conditions & References With ethanol, copper dichloride, T= 22 °C , further catalysts; pseudo-first-order rate constants for ethanolysis reactions, Rate constant Carpanelli, Corrado; Gaiani, Giovanni; Gazzetta Chimica Italiana; vol. 113; nb. 7/8; (1983); p. 503 - 506 View in Reaxys

N S

H 2N

Rx-ID: 2105979 View in Reaxys 229/630 Yield

Conditions & References With ethanol, copper dichloride, T= 22 °C , pseudo-first-order rate constants for ethanolysis reactions, Rate constant Carpanelli, Corrado; Gaiani, Giovanni; Gazzetta Chimica Italiana; vol. 113; nb. 7/8; (1983); p. 503 - 506 View in Reaxys

NH 2

Rx-ID: 2109424 View in Reaxys 230/630 Yield

NH 2

Rx-ID: 2109425 View in Reaxys 231/630 Yield

N O

NH 2

Rx-ID: 2111685 View in Reaxys 232/630 Yield

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2016-05-04 01:50:52

O O

NH 2

Rx-ID: 2171266 View in Reaxys 233/630 Yield

N O

O O

NH 2

Rx-ID: 2191224 View in Reaxys 234/630 Yield

N S

H 2N

Rx-ID: 2193766 View in Reaxys 235/630 Yield

O+ H

Rx-ID: 2340667 View in Reaxys 236/630 Yield

O+ H

N O

Rx-ID: 2342390 View in Reaxys 237/630 Yield

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Rx-ID: 2612922 View in Reaxys 238/630 Yield

Conditions & References in cyclohexane, T= 20 °C , Equilibrium constant Bellon, Louis; Taft, Robert W.; Abboud, Jose-Luis M.; Journal of Organic Chemistry; vol. 45; nb. 6; (1980); p. 1166 - 1168 View in Reaxys

O+ H

E O+

Rx-ID: 3382681 View in Reaxys 239/630 Yield

O+ H

+HO

Rx-ID: 3383641 View in Reaxys 240/630 Yield

NH 2

Rx-ID: 3577359 View in Reaxys 241/630 Yield

Al2O3

butylenene

Rx-ID: 6210757 View in Reaxys 242/630 Yield

Conditions & References T= 420 °C Quattlebaum; Toussaint; Dunn; Journal of the American Chemical Society; vol. 69; (1947); p. 597 View in Reaxys Br O O

zinc

Br O

Rx-ID: 7059329 View in Reaxys 243/630 Yield

Conditions & References T= 160 °C

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Beyerstedt; McElvain; Journal of the American Chemical Society; vol. 59; (1937); p. 1274 View in Reaxys Br

Rx-ID: 9448917 View in Reaxys 244/630 Yield

Conditions & References With zirconium oxide, copper(II) oxide, T= 250 °C , Product distribution, Further Variations: Reagents, Temperatures Zhou, Xiao-Ping; Yilmaz, Aysen; Yilmaz, Gurkan A.; Lorkovic, Ivan M.; Laverman, Leroy E.; Weiss, Michael; Sherman, Jeffrey H.; McFarland, Eric W.; Stucky, Galen D.; Ford, Peter C.; Chemical Communications; nb. 18; (2003); p. 2294 - 2295 View in Reaxys

(v5)

(v6)ClCl

Rx-ID: 26365872 View in Reaxys 245/630 Yield

Conditions & References 60-70°C Thiele; Wagner; Journal of Organometallic Chemistry; vol. 20; (1969); p. P25,P26 View in Reaxys vol. V: Org.Verb.; 1.3, page 9 - 10 ; (from Gmelin) View in Reaxys

HH (v4) H N

(v4)

H B+H

Cl –

(v4)

N H HH

Rx-ID: 26647112 View in Reaxys 246/630 Yield

Conditions & References in diethyl ether, introduction of NH3 into soln. of (C2H5)2O*BH2Cl Noeth, H.; Beyer, H.; Vetter, H. J.; Chemische Berichte; vol. 97; (1964); p. 110 - 118 ; (from Gmelin) View in Reaxys OH

Rx-ID: 40073772 View in Reaxys 247/630 Yield

Conditions & References With water, hydrogen peroxide in [D3]acetonitrile, Time= 23h, T= 24.84 °C , Catalytic behavior Aratani, Yusuke; Yamada, Yusuke; Fukuzumi, Shunichi; Chemical Communications; vol. 51; nb. 22; (2015); p. 4662 - 4665 View in Reaxys

O ClIMg

Rx-ID: 537306 View in Reaxys 248/630 Yield

Conditions & References T= 10 °C , p= 15Torr , Geschwindigkeit Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys T= 10 °C , Geschwindigkeit im Hochvakuum

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Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys

N OH

NH 2

Rx-ID: 1871462 View in Reaxys 249/630 Yield

Conditions & References

91 %, 70 %, 93.6 % Chromat.

With copper dichloride, Time= 24h, Ambient temperature, other reagent, Product distribution Carpanelli, Corrado; Gaiani, Giovanni; Albini, Adriana; Gazzetta Chimica Italiana; vol. 112; nb. 9/10; (1982); p. 409 - 414 View in Reaxys

Rx-ID: 2899766 View in Reaxys 250/630 Yield

Conditions & References With hydrogen, Rh-Sn, silica gel, Time= 18.5h, p= 37503Torr , var. time and Sn/Rh-rate, Product distribution Mansour, Abdellah El; Candy, Jean P.; Bournonville, Jean P.; Ferretti, Osmar A.; Basset, Jean-Marie; Angewandte Chemie; vol. 101; nb. 3; (1989); p. 360 - 362 View in Reaxys

Al2O3

Rx-ID: 6946422 View in Reaxys 251/630 Yield

Conditions & References T= 420 °C Quattlebaum; Toussaint; Dunn; Journal of the American Chemical Society; vol. 69; (1947); p. 597 View in Reaxys

oxygen

Rx-ID: 7978972 View in Reaxys 252/630 Yield

Conditions & References T= -40 - 25 °C , und andere Produkte: Aethoxy-diaethyl-bismutin, Bi2O3 Calingaert; Soroos; Hnizda; Journal of the American Chemical Society; vol. 64; (1942); p. 392 View in Reaxys

O F F

B– FF

(v3)

Ag+ (v3) (v3)

(v3)

Rx-ID: 26171173 View in Reaxys 253/630 Yield

Conditions & References at room temp., in vac., decompn. Meerwein, H.; Hederich, V.; Wunderlich, K.; Archiv der Pharmazie (Weinheim, Germany); vol. 291; (1958); p. 541 - 554 View in Reaxys vol. Ag: MVol.B6; 1.8.1, page 218 - 218 ; (from Gmelin)

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View in Reaxys

(v3)

B– (v3)

B–

Na +

Rx-ID: 26614131 View in Reaxys 254/630 Yield

Conditions & References at 180°C Krause, E.; Polack, H.; Ber. Dtsch. Chem. Ges.; vol. 59; (1926); p. 777 - 785 View in Reaxys Krause, E.; Ber. Dtsch. Chem. Ges.; vol. 57; (1924); p. 216 - 217 ; (from Gmelin) View in Reaxys at 180°C vol. Na: SVol.3; 3.8.2, page 1248 - 1252 ; (from Gmelin) View in Reaxys

(v2)

(v6)H (v6) H B(v2) (v6) B H (v4) H(v6) B HH B Zn 2 B H BH BB H(v6) (v6) B(v6) H H (v6) B (v6) H (v6)

Rx-ID: 26615007 View in Reaxys 255/630 Yield

Conditions & References decompn. above 130°C Greenwood, N. N.; Travers, N. F.; Journal of the Chemical Society [Section] A: Inorganic, Physical, Theoretical; (1967); p. 880 - 884 ; (from Gmelin) View in Reaxys decompn. above 130°C vol. B: B-Verb.3; 11.9.3, page 198 - 200 ; (from Gmelin) View in Reaxys

Br SbBr Br

Rx-ID: 26632890 View in Reaxys 256/630 Yield

Conditions & References 55 °C Raynaud, A.; Bulletin de la Societe Chimique de France; vol. 27; (1920); p. 411 ; (from Gmelin) View in Reaxys 55 °C vol. Sb: MVol.B2; 12.3, page 480 - 482 ; (from Gmelin) View in Reaxys

O O

Cl 2Mg

Rx-ID: 628945 View in Reaxys 257/630

109/278

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Yield

Conditions & References T= 63 °C , p= 15Torr , Geschwindigkeit Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys

O– Na +

O O

O O O

Rx-ID: 671631 View in Reaxys 258/630 Yield

Conditions & References T= 220 - 230 °C , Produkt 5: Aethanol; Produkt 6: CO Cope; McElvain; Journal of the American Chemical Society; vol. 54; p. 4323 View in Reaxys O

S O

Rx-ID: 1699851 View in Reaxys 259/630 Yield

Conditions & References

17 %, 12 %, 37 %, 16 %

in N,N-dimethyl-formamide, T= 20 °C , electrolysis, oth. solvent, var. cathodes, Product distribution Nonaka; Kihara; Fuchigami; Baizer; Bulletin of the Chemical Society of Japan; vol. 57; nb. 11; (1984); p. 3160 3166 View in Reaxys

H 2N

Rx-ID: 1871418 View in Reaxys 260/630 Yield

Conditions & References

84 %, 80 %, 72 %

With copper dichloride, Time= 24h, Ambient temperature, other catlysts, subst. effects, further solvent, Product distribution Carpanelli, Corrado; Gaiani, Giovanni; Albini, Adriana; Gazzetta Chimica Italiana; vol. 112; nb. 9/10; (1982); p. 409 - 414 View in Reaxys

Rx-ID: 1878330 View in Reaxys 261/630 Yield

Conditions & References With hydrogen, NiOs3(η-C5H5)(μ-H)2(Cu(PPh3))(CO)9, T= 230 °C , other temp., Product distribution Castagno, Fabrizio; Castiglioni, Mario; Sappa, Enrico; Tiripicchio, Antonio; Camellini, Marisa Tiripicchio; et al.; Journal of the Chemical Society, Dalton Transactions: Inorganic Chemistry (1972-1999); (1989); p. 1477 - 1482 View in Reaxys

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-1 F (v4)

B FF

O+

Rx-ID: 2618923 View in Reaxys 262/630 Yield

Conditions & References With potassium hydroxide in various solvent(s), Time= 0.5h, Ambient temperature, Product distribution Olah, George A.; Doggweiler, Hans; Felberg, Jeff D.; Journal of Organic Chemistry; vol. 49; nb. 12; (1984); p. 2116 - 2120 View in Reaxys

ethyl sulfate

Rx-ID: 6918333 View in Reaxys 263/630 Yield

Conditions & References Hydrolysis Patent; Union Carbide and Carbon Corp.; US2050600; (1933) View in Reaxys

B2O3

pumice stone

Rx-ID: 6918338 View in Reaxys 264/630 Yield

Conditions & References T= 330 - 340 °C , p= 18387.7Torr , 1/3 Vol. Wasserdampf Dreyfus; Chem. Zentralbl.; vol. 105; nb. II; (1934); p. 3180 View in Reaxys Patent; Dreyfus; US2084390; (1933) View in Reaxys Patent; Dreyfus; GB408304 View in Reaxys

-1

O O

-1 Cl 2Fe

Rx-ID: 26151612 View in Reaxys 265/630 Yield

Conditions & References loss of ether on heating to 100°C; Manchot, W.; Haas, J.; Ber.; vol. 45; (1912); p. 3052 - 3052 View in Reaxys vol. Fe: MVol.B1; 97, page 219 - 220 ; (from Gmelin) View in Reaxys

O P

Rx-ID: 26153517 View in Reaxys 266/630 Yield

Conditions & References 150°C; isolated by gas cromatography Dolan, D. N.; Nickless, G.; Journal of Chromatography; vol. 37; (1968); p. 1 - 13 ; (from Gmelin)

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View in Reaxys 150°C; isolated by gas cromatography vol. Sn: Org.Verb.1; 1.1.1.1.4.6, page 49 - 52 ; (from Gmelin) View in Reaxys

(v2)

(v6)H (v6) H B(v2) (v6) B H (v4) H(v6) B HH B Cd B B 2 H B H(v6)B (v6) B(v6)H H H (v6) B (v6) H (v6)

Rx-ID: 26612948 View in Reaxys 267/630 Yield

Conditions & References decompn. in vac. Greenwood, N. N.; McGinnety, J. A.; Owen, J. D.; Journal of the Chemical Society; (1972); p. 989 - 992 View in Reaxys vol. B: B-Verb.3; 11.9.3, page 198 - 200 ; (from Gmelin) View in Reaxys

N H

B N

Rx-ID: 26647108 View in Reaxys 268/630 Yield

Conditions & References in diethyl ether, equimolar amts. of (C2H5)2O*BH2Cl and ((CH3)3Si)2NH, strongly exothermic react. Zhigach, A. F.; Sobolev, E. S.; Svitsyn, R. A.; Nikitin, V. S.; Zhurnal Obshchei Khimii; vol. 43; (1973); p. 1949 1953; Zhurnal Obshchei Khimii; vol. 43; (1973); p. 1966 - 1971 ; (from Gmelin) View in Reaxys

OH HO

Rx-ID: 26804710 View in Reaxys 269/630 Yield

Conditions & References in benzene Davies, A. G.; Hook, S. C. W.; Journal of the Chemical Society [Section] C: Organic; (1971); p. 1660 - 1665 View in Reaxys vol. Bi: Org.Verb.; 1.4.1.1.4, page 102 - 103 ; (from Gmelin) View in Reaxys O

S O

Rx-ID: 102246 View in Reaxys 270/630 Yield

Conditions & References Erlenmeyer,E.; Justus Liebigs Annalen der Chemie; vol. 162; (1872); p. 379 View in Reaxys With sodium hydroxide, water, Mechanismus der Bildung Lauder; Green; Transactions of the Faraday Society; vol. 44; (1948); p. 809 View in Reaxys With cupro oxide Recoura; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 148; (1909); p. 1108

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View in Reaxys Lander; Green; Transactions of the Faraday Society; vol. 44; (1948); p. 808 View in Reaxys Al3+ 3

O– O

Rx-ID: 537853 View in Reaxys 271/630 Yield

Conditions & References Tischtschenko; Chem. Zentralbl.; vol. 71; nb. I; (1900); p. 585 View in Reaxys

O O

Br2Mg

Rx-ID: 628944 View in Reaxys 272/630 Yield

Conditions & References T= 25 °C , Geschwindigkeit; im Vakuum Meisenheimer; Casper; Chemische Berichte; vol. 54; (1921); p. 1663 View in Reaxys T= 63 °C , Geschwindigkeit Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys T= 25 °C , Geschwindigkeit Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys T= 10 °C , Geschwindigkeit Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys -1 I

O+

I (v3)

HgI 2

Rx-ID: 26144155 View in Reaxys 273/630 Yield

Conditions & References ambient temp.; 24 h Meerwein, H.; Battenberg, E.; Gold, H.; Pfeil, E.; Willfang, G.; J. Prakt. Chem. (2); vol. 154; (1940); p. 83 - 156 ; (from Gmelin) View in Reaxys ambient temp.; 24 h vol. Hg: MVol.B4; 20.1, page 1544 - 1549 ; (from Gmelin) View in Reaxys O

B F

F O

F B

F O

Rx-ID: 26147944 View in Reaxys 274/630 Yield

Conditions & References Patent; McAda, R. W.; US3597502; (1971); C.A.; vol. 75; (1971); p. 110552 ; (from Gmelin) View in Reaxys

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vol. B: B-Verb.3; 6.5.2, page 129 - 136 ; (from Gmelin) View in Reaxys

C 0.28H 0.63BiO2.5

Rx-ID: 26519187 View in Reaxys 275/630 Yield

Conditions & References byproducts: ethanol Davies, A. G.; Hook, S. C. W.; Journal of the Chemical Society [Section] C: Organic; (1971); p. 1660 - 1665 ; (from Gmelin) View in Reaxys byproducts: ethanol vol. Bi: Org.Verb.; 1.3.3.1.1, page 46 - 55 ; (from Gmelin) View in Reaxys -1

F (v4)

B FF

I O

O+

Rx-ID: 30029810 View in Reaxys 276/630 Yield

Conditions & References With sodium tetrahydroborate, iodine, potassium iodide, sodium hydroxide in dichloromethane, water, toluene, Time= 4.16667h, Kinetics, Temperature, Reagent/catalyst Manion, Bruce A.; Holbein, Bruce E.; Marcone, Massimo F.; Seetharaman, Koushik; Carbohydrate Research; vol. 345; nb. 18; (2010); p. 2698 - 2704 View in Reaxys

CH 2

(v1)

Rx-ID: 169965 View in Reaxys 277/630 Yield

Conditions & References Wijnen; Journal of the American Chemical Society; vol. 80; (1958); p. 2394 View in Reaxys

O– Na +

Rx-ID: 178590 View in Reaxys 278/630 Yield

Conditions & References Beilstein; Justus Liebigs Annalen der Chemie; vol. 112; (1859); p. 123 View in Reaxys

P O

Rx-ID: 2184491 View in Reaxys 279/630 Yield

Conditions & References in chloroform, T= 25 °C , decomposition

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Robinson, Philip L.; Kelly, Jeffery W.; Evans, Slayton A.; Phosphorus and Sulfur and the Related Elements; vol. 26; (1986); p. 15 - 24 View in Reaxys

O O

Rx-ID: 2404423 View in Reaxys 280/630 Yield

Conditions & References With potassium hydroxide, 3-chloro-3-methyl-1-butene in benzene, T= 40 °C , further reagents Esikova, I. A.; Yufit, S. S.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 29; nb. 3; (1980); p. 328 - 335; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; nb. 3; (1980); p. 507 - 514 View in Reaxys

H+

H 2N

H+

Rx-ID: 3137961 View in Reaxys 281/630 Yield

Conditions & References enthalpy and entropy changes for the complex dissociation reaction: ΔH0 D, ΔS0 D, Thermodynamic data Meot-Ner (Mautner), Michael; Journal of the American Chemical Society; vol. 105; nb. 15; (1983); p. 4912 - 4915 View in Reaxys

H+

Rx-ID: 3144483 View in Reaxys 282/630 Yield

O H

H+

H 2N

H+

Rx-ID: 3156846 View in Reaxys 283/630 Yield

O H

H+

Rx-ID: 3157010 View in Reaxys 284/630

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Yield

Conditions & References enthalpy change for the complex dissociation reaction: ΔH0 D, Thermodynamic data Meot-Ner (Mautner), Michael; Journal of the American Chemical Society; vol. 105; nb. 15; (1983); p. 4912 - 4915 View in Reaxys N

N H+

O H+

Rx-ID: 3159894 View in Reaxys 285/630 Yield

Rx-ID: 3450337 View in Reaxys 286/630 Yield

Conditions & References Time= 24h, Heating, Yield given. Yields of byproduct given Nitta; Arakawa; Chemical &amp; pharmaceutical bulletin; vol. 33; nb. 4; (1985); p. 1711 - 1715 View in Reaxys

Rx-ID: 3852147 View in Reaxys 287/630 Yield

Conditions & References With hydrogen, iodine, pressure, temperature effect on products distribution, Mechanism, Product distribution Jenner G.; Tetrahedron Letters; vol. 29; nb. 20; (1988); p. 2445 - 2448 View in Reaxys Cl

Cl O

O Cl

Rx-ID: 4965811 View in Reaxys 288/630 Yield

Conditions & References in cyclohexane, T= 24.9 °C , Equilibrium constant Abraham, Michael H.; Prior, David V.; Schulz, Ronald A.; Morris, Jeffrey J.; Taylor, Peter J.; Journal of the Chemical Society - Faraday Transactions; vol. 94; nb. 7; (1998); p. 879 - 885 View in Reaxys Cl

Cl O

O Cl

Rx-ID: 4965847 View in Reaxys 289/630 Yield

Conditions & References in cyclohexane, T= 24.9 °C , Equilibrium constant

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Abraham, Michael H.; Prior, David V.; Schulz, Ronald A.; Morris, Jeffrey J.; Taylor, Peter J.; Journal of the Chemical Society - Faraday Transactions; vol. 94; nb. 7; (1998); p. 879 - 885 View in Reaxys O

Rx-ID: 5090517 View in Reaxys 290/630 Yield

Conditions & References

10.6 % Chromat., 25.6 % Chromat., 62.2 % Chromat., 0.2 % Chromat., 1.4 % Chromat.

With carbon AZ20-0.5, Time= 2h, T= 179.85 °C , various activated carbons, Product distribution Carrasco-MariI n; Mueden; Moreno-Castilla; Journal of Physical Chemistry B; vol. 102; nb. 46; (1998); p. 9239 9244 View in Reaxys

palladium

Rx-ID: 5802857 View in Reaxys 291/630 Yield

Conditions & References Hydrogenation Jacobs; Cramer; Hanson; Journal of the American Chemical Society; vol. 64; (1942); p. 225 View in Reaxys OH

platinum

Rx-ID: 5802858 View in Reaxys 292/630 Yield

Conditions & References Hydrogenation Jacobs; Cramer; Hanson; Journal of the American Chemical Society; vol. 64; (1942); p. 225 View in Reaxys O

O O

ZnCl2

Rx-ID: 6188342 View in Reaxys 293/630 Yield

Conditions & References bei der Destillation Underwood; Baril; Journal of the American Chemical Society; vol. 57; (1935); p. 2729 View in Reaxys

(v4)

Al O (v3)

Rx-ID: 26109036 View in Reaxys 294/630 Yield

Conditions & References Kinetics, thermal dissociation, above 373 K; products not isolated, reaction monitoring by pressure measurement Yablokov; Mitrofanova; Bulychev; Russian Journal of General Chemistry; vol. 67; nb. 4; (1997); p. 505 - 509 ; (from Gmelin) View in Reaxys

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(v2)

2.5

Rx-ID: 26355732 View in Reaxys 295/630 Yield

Conditions & References thermal decompn. at about 200°C Razuvaev, G. A.; Latyaeva, V. N.; Zateev, B. G.; Kilyakova, G. A.; Doklady Akademii Nauk SSSR; vol. 172; (1967); p. 180 - 182; Doklady Akademii Nauk SSSR; vol. 172; (1967); p. 1337 - 1339 ; (from Gmelin) View in Reaxys thermal decompn. at about 200°C vol. V: Org.Verb.; 1.1.1, page 1 - 3 ; (from Gmelin) View in Reaxys

B– HH

Be2+

BeH 2

B H

H P

Rx-ID: 26615312 View in Reaxys 296/630 Yield

Conditions & References BeH2 sepd. with boiling benzene Patent; Kratzer, R.; Kazimiera, K. J. L.; US3729552; (1973); C.A.; vol. 79; (1973); p. 7578 ; (from Gmelin) View in Reaxys BeH2 sepd. with boiling benzene vol. B: B-Verb.3; 6.5.1, page 117 - 129 ; (from Gmelin) View in Reaxys O

O Mo

(v6)

O Mo SP-4 (v6)

Rx-ID: 26627792 View in Reaxys 297/630 Yield

Conditions & References exclusion of atmospheric moisture; room temp. Obvintseva, I. E.; Yanovskaya, M. I.; Kessler, V. G.; Shifrina, R. R.; Turova, N. Ya.; Russian Journal of Inorganic Chemistry (Translation of Zhurnal Neorganicheskoi Khimii); vol. 34; (1989); p. 1432 - 1435; Zhurnal Neorganicheskoi Khimii; vol. 34; (1989); p. 2505 - 2511 ; (from Gmelin) View in Reaxys

Si N

B H

Cl O

Si N

Rx-ID: 26647109 View in Reaxys 298/630 Yield

Conditions & References <60°C Zhigach, A. F.; Sobolev, E. S.; Svitsyn, R. A.; Nikitin, V. S.; Zhurnal Obshchei Khimii; vol. 43; (1973); p. 1949 1953; Zhurnal Obshchei Khimii; vol. 43; (1973); p. 1966 - 1971 ; (from Gmelin) View in Reaxys <60°C

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vol. B: B-Verb.9; 1.4.3.3, page 41 - 44 ; (from Gmelin) View in Reaxys

Si N

B H

Cl Si

(v2)

H H B B H (v4)H (v4) H (v2)

Rx-ID: 26647110 View in Reaxys 299/630 Yield

Conditions & References 3-fold molar amt. of (C2H5)2O*BH2Cl Zhigach, A. F.; Sobolev, E. S.; Svitsyn, R. A.; Nikitin, V. S.; Zhurnal Obshchei Khimii; vol. 43; (1973); p. 1949 1953; Zhurnal Obshchei Khimii; vol. 43; (1973); p. 1966 - 1971 ; (from Gmelin) View in Reaxys 3-fold molar amt. of (C2H5)2O*BH2Cl vol. B: B-Verb.9; 1.4.3.3, page 41 - 44 ; (from Gmelin) View in Reaxys

O+ C– O

O Cl

N O

Rx-ID: 32682267 View in Reaxys 300/630 Yield

Conditions & References in pentane, T= 21.84 °C , Kinetics Hoijemberg, Pablo A.; Moss, Robert A.; Krogh-Jespersen, Karsten; Journal of Physical Chemistry A; vol. 116; nb. 1; (2012); p. 358 - 363 View in Reaxys

(v3) (v3) Li+ O (v4) – (v3)

(v3)

–

O Li+

(v3) (v3) Li+

C– (v3)

Rx-ID: 34953608 View in Reaxys 301/630 Yield

Conditions & References in deuterated toluene, T= 25 °C , Equilibrium constant, Thermodynamic data, Temperature, Concentration Knorr, Rudolf; Menke, Thomas; Ferchland, Kathrin; Organometallics; vol. 32; nb. 2; (2013); p. 468 - 472 View in Reaxys

Rx-ID: 37232841 View in Reaxys 302/630 Yield

Conditions & References With water, T= 299.84 °C , Flow reactor, Inert atmosphere, Catalytic behavior Riani, Paola; Garbarino, Gabriella; Lucchini, Mattia Alberto; Canepa, Fabio; Busca, Guido; Journal of Molecular Catalysis A: Chemical; vol. 383-384; (2014); p. 10 - 16 View in Reaxys

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O O

Rx-ID: 40924860 View in Reaxys 303/630 Yield

Conditions & References With hierarchical-HZ-5, Time= 2h, T= 99.84 °C , Green chemistry, Catalytic behavior Nandiwale, Kakasaheb Y.; Pande, Ashwini M.; Bokade, Vijay V.; RSC Advances; vol. 5; nb. 97; (2015); p. 79224 - 79231 View in Reaxys

Br–+Mg

Rx-ID: 374647 View in Reaxys 304/630 Yield

Conditions & References Mc Kenzie; Wren; Journal of the Chemical Society; vol. 97; (1910); p. 477 View in Reaxys

OH O Br–+Mg

Rx-ID: 588728 View in Reaxys 305/630 Yield

Conditions & References Mc Kenzie; Wren; Journal of the Chemical Society; vol. 97; (1910); p. 477 View in Reaxys

O N

E N

N Z

O O

Rx-ID: 805869 View in Reaxys 306/630 Yield

Conditions & References Brady; Goldstein; Journal of the Chemical Society; (1927); p. 1961 View in Reaxys Minunni; Vassallo; Gazzetta Chimica Italiana; vol. 26 I; (1896); p. 463 View in Reaxys

O Mg+

Mg+

O (v0)

(v0)

Yield

Rx-ID: 1456847 View in Reaxys 307/630

Conditions & References Ambient temperature, gas phase reaction, ΔGexch, Rate constant, Equilibrium constant, Thermodynamic data

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Operti, Lorenza; Tews, Edward C.; Freiser, Ben S.; Journal of the American Chemical Society; vol. 110; nb. 12; (1988); p. 3847 - 3853 View in Reaxys

S O

O S

O O S

O S

Rx-ID: 1699849 View in Reaxys 308/630 Yield

Conditions & References With sulfur trioxide, Time= 1h, T= 25 °C , var. temp., Product distribution Andrashchuk, N. P.; Moskvichev, Yu. A.; Shapiro, Yu. E.; Shutova, I. V.; Timoshenko, G. N.; Belyaeva, S. S.; Journal of Organic Chemistry USSR (English Translation); vol. 26; nb. 6.1; (1990); p. 1075 - 1079; Zhurnal Organicheskoi Khimii; vol. 26; nb. 6; (1990); p. 1244 - 1249 View in Reaxys

Rx-ID: 1878297 View in Reaxys 309/630 Yield

Conditions & References With B-C1 alumino borate, T= 249.9 °C , var. temp.; diethyl ether, Product distribution Xu, Bo-Qing; Cai, Tian-Xi; Yu, Ji-Hong; Xiao, Feng-Shou; Xu, Ru-Ren; et al.; Journal of the Chemical Society, Chemical Communications; nb. 17; (1992); p. 1228 - 1229 View in Reaxys

Mg+

(v0)

Yield

Rx-ID: 2896899 View in Reaxys 310/630

Conditions & References Ambient temperature, gas phase reaction, ΔGexch, Rate constant, Equilibrium constant, Thermodynamic data Operti, Lorenza; Tews, Edward C.; Freiser, Ben S.; Journal of the American Chemical Society; vol. 110; nb. 12; (1988); p. 3847 - 3853 View in Reaxys OH

Mg+

O (v0)

(v0)

Yield

Rx-ID: 3516768 View in Reaxys 311/630

Mg+

O Mg+

O (v0)

(v0)

Yield

Rx-ID: 3527118 View in Reaxys 312/630

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2016-05-04 01:50:52

HN P

NH 2

H N

H N N H

P O

Rx-ID: 4873077 View in Reaxys 313/630 Yield

Conditions & References in benzene, T= 25 °C , Rate constant Yanchuk; Russian Journal of General Chemistry; vol. 67; nb. 2; (1997); p. 220 - 223 View in Reaxys

HN P

NH 2

H N

H N N H

P O

Rx-ID: 4882134 View in Reaxys 314/630 Yield

Conditions & References in benzene, T= 25 °C , Rate constant Yanchuk; Russian Journal of General Chemistry; vol. 67; nb. 2; (1997); p. 220 - 223 View in Reaxys

OH HO

S OO

H N NH 2

Rx-ID: 6918329 View in Reaxys 315/630 Yield

Conditions & References T= 130 - 300 °C , p= 147102 - 220652Torr Universal Oil Prod. Co; ; (1940); p. 1333 View in Reaxys Patent; Universal Oil Prod. Co.; US2179092; (1932) View in Reaxys

petroleum ether

Rx-ID: 6918335 View in Reaxys 316/630 Yield

Conditions & References T= 25 °C , Geschwindigkeit Gilman et al.; Journal of Organic Chemistry; vol. 19; (1954); p. 1034,1038,1039 View in Reaxys

petroleum ether

Rx-ID: 6918336 View in Reaxys 317/630 Yield

Conditions & References T= 25 °C , Geschwindigkeit Gilman et al.; Journal of Organic Chemistry; vol. 19; (1954); p. 1034,1038,1039 View in Reaxys

petroleum ether

Rx-ID: 6918337 View in Reaxys 318/630

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Yield

Conditions & References T= 25 °C , Geschwindigkeit Gilman et al.; Journal of Organic Chemistry; vol. 19; (1954); p. 1034,1038,1039 View in Reaxys

platinum oxide

Rx-ID: 7058018 View in Reaxys 319/630 Yield

Conditions & References Hydrogenation Ruigh; Major; Journal of the American Chemical Society; vol. 53; (1931); p. 2664,2670 View in Reaxys

O S

SO2

Rx-ID: 7086595 View in Reaxys 320/630 Yield

Conditions & References je nach den Reaktionsbedingungen Bissinger; Kung; Hamilton; Journal of the American Chemical Society; vol. 70; (1948); p. 3941 View in Reaxys

O S

SO2

Rx-ID: 7086597 View in Reaxys 321/630 Yield

Conditions & References je nach den Reaktionsbedingungen Bissinger; Kung; Hamilton; Journal of the American Chemical Society; vol. 70; (1948); p. 3941 View in Reaxys

N O

NH 2

N2 Rx-ID: 8427235 View in Reaxys 322/630

Yield

Conditions & References With Cu(2+), T= 35 °C , Rate constant, Mechanism Iley, Jim; Moreira, Rui; Rosa, Eduarda; Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999); nb. 1; (1991); p. 81 - 86 View in Reaxys

B F

B B F

Rx-ID: 26792755 View in Reaxys 323/630

123/278

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Yield

Conditions & References 120°C, catalyst Koester, R.; Grassberger, M. A.; Liebigs Annalen der Chemie; vol. 719; (1968); p. 169 - 186 View in Reaxys vol. B: B-Verb.9; 6.1, page 258 - 268 ; (from Gmelin) View in Reaxys

B B

Rx-ID: 26792756 View in Reaxys 324/630 Yield

Rx-ID: 40295685 View in Reaxys 325/630 Yield 0.6 %, 1.4 %, 0.8 %, 22.4 %, 0.2 %, 1.1 %, 0.5 %, 0.1 % 0.4 %, 1.6 %, 1.2 %, 15.2 %, 0.2 %, 0.7 %, 0.2 %, 0.3 % 0.2 %, 2.6 %, 1.2 %, 7.7 %, 0.6 %, 0.4 %, 0.2 %, 0.1 % 0.1 %, 1.5 %, 0.7 %, 4.4 %, 0.3 %, 0.1 %, 0.05 %, 0.1 %

Conditions & References With carbonated carbonate-containing hydroxyapatites (Hap-CO3), T= 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 40 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With carbonated carbonate-containing hydroxyapatites (HapNa-CO3), T= 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 26 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With carbonated carbonate-containing hydroxyapatites (HapE-CO3), T= 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 17 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With carbonated carbonate-containing hydroxyapatites (HapE-CO3), T= 350 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 9 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006

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View in Reaxys 0.3 %, 2.3 %, 1.1 %, 4.9 %, 1.2 %, 0.2 %, 0.1 %, 0.2 %

With carbonated carbonate-containing hydroxyapatites (HapE-Na-CO3), T= 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 12 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys

Rx-ID: 40295687 View in Reaxys 326/630 Yield 11.4 %, 3.1 %, 0.2 %, 21.5 %, 2.0 %, 3.3 %, 0.8 %

1.4 %, 2.6 %, 0.1 %, 18.2 %, 1.2 %, 1.2 %, 0.3 %

0.2 %, 0.7 %, 0.5 %, 10.6 %, 0.2 %, 0.3 %, 0.1 %

Conditions & References With stoichiometric carbonate-containing hydroxyapatites (Hap), T= 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 65.1 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With stoichiometric carbonate-containing hydroxyapatites (Hap), T= 350 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 32.2 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys With carbonated carbonate-containing hydroxyapatites (Hap-CO3), T= 350 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 15.2 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys

H 2Si

SiH

Rx-ID: 41478219 View in Reaxys 327/630 Yield

Conditions & References With [{κ3-N,Si,C-PhB(4,4-dimethyl-2-oxazoline)((4,4-dimethyl-2-oxazoline)SiHPh)(1-mesitylimidazole)}Rh(H)CO] [HB(C6F5)3], T= 25 °C , Inert atmosphere, Schlenk technique, Glovebox, Catalytic behavior Xu, Songchen; Boschen, Jeffery S.; Biswas, Abhranil; Kobayashi, Takeshi; Pruski, Marek; Windus, Theresa L.; Sadow, Aaron D.; Dalton Transactions; vol. 44; nb. 36; (2015); p. 15897 - 15904 View in Reaxys

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Rx-ID: 6558 View in Reaxys 328/630 Yield

Conditions & References Schamschurin; ; Univ. 15 <1939> 33, 38; ; (1941); p. 3994 View in Reaxys

–C

N+

O O

Rx-ID: 31231 View in Reaxys 329/630 Yield

Conditions & References Ridi; Gazzetta Chimica Italiana; vol. 71; (1941); p. 462,464 View in Reaxys

O O S

O S OH

Rx-ID: 189585 View in Reaxys 330/630 Yield

Conditions & References T= 140 °C , man destilliert kontinuerlich der gebildete Aether ueber Schroeter; Sondag; Chemische Berichte; vol. 41; (1908); p. 1921; Chem. Zentralbl.; vol. 79; nb. II; (1908); p. 551 View in Reaxys Patent; Schroetter; Sondag; DE200150 View in Reaxys T= 140 °C Schroeter; Sondag; Chemische Berichte; vol. 41; (1908); p. 1921; Chem. Zentralbl.; vol. 79; nb. II; (1908); p. 551 View in Reaxys Schroeter; Sondag; Chemische Berichte; vol. 41; (1908); p. 1921; Chem. Zentralbl.; vol. 79; nb. II; (1908); p. 551 View in Reaxys N

H H 2N

Rx-ID: 600032 View in Reaxys 331/630 Yield

Conditions & References Bucherer; Grolee; Chemische Berichte; vol. 39; (1906); p. 992 View in Reaxys N

Cl H 2N

Rx-ID: 600034 View in Reaxys 332/630 Yield

Conditions & References Bucherer; Grolee; Chemische Berichte; vol. 39; (1906); p. 992

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View in Reaxys O

O C

Rx-ID: 1922730 View in Reaxys 333/630 Yield

Conditions & References With [RuIII(2,4-pentanedionato)3], dicobalt octacarbonyl, methyl iodide, Time= 17.5h, T= 180 °C , other ester; other ruthenium-cobalt, ruthenium and cobalt catalysts, Product distribution Hidai, Masanobu; Koyasu, Yukio; Yokota, Makoto; Orisaku, Masami; Uchida, Yasuzo; Bulletin of the Chemical Society of Japan; vol. 55; nb. 12; (1982); p. 3951 - 3952 View in Reaxys

Rx-ID: 2867680 View in Reaxys 334/630 Yield

Conditions & References With titanium oxide-vanadium oxide, T= 350 °C , var. ratio of reaction partners, var. amounts of reagents, Product distribution, Rate constant WANG, Fey-long; LIN, Yi-hsuan; Chemistry Letters; nb. 9; (1992); p. 1867 - 1868 View in Reaxys O

Rx-ID: 4354363 View in Reaxys 335/630 Yield

Conditions & References With H-clinoptilolite, T= 200 °C , var. temp. and zeolites, Product distribution Shakhtakhtinskii, T. N.; Aliev, A. M.; Kuliev, A. R.; Medzhidova, S. M.; Muradov, M. Kh.; Doklady Chemistry; vol. 343; nb. 4-6; (1995); p. 175 - 178; Doklady Akademii Nauk; vol. 343; nb. 4; (1995); p. 489 - 492 View in Reaxys O

N O

HN P

NH 2

N O

N O O N

N O

O O

NH 2

P Cl

Rx-ID: 4864079 View in Reaxys 336/630 Yield

Conditions & References in benzene, T= 25 °C , Rate constant Yanchuk; Russian Journal of General Chemistry; vol. 67; nb. 2; (1997); p. 220 - 223 View in Reaxys

I O

N H

Na +

H –N

O H 2N

Rx-ID: 5459722 View in Reaxys 337/630

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Yield

Conditions & References Gilman; Avakian; Journal of the American Chemical Society; vol. 67; (1945); p. 349 View in Reaxys -2 OH HO

S OO

(v1)

Cu 2+

(v1)

S O

Rx-ID: 6931649 View in Reaxys 338/630 Yield

Conditions & References T= 60 °C , p= 3677.5 - 4413.05Torr , anschl. Destillieren mit Wasserdampf Patent; Dow Chem. Co.; US2210316; (1937); Fortschr. Teerfarbenfabr. Verw. Industriezweige; 1941 134 View in Reaxys OH

aluminium oxide silicon dioxide

Rx-ID: 7053575 View in Reaxys 339/630 Yield

Conditions & References T= 170 - 465 °C , Kinetics Roy; Bose; ; vol. 11; (1958); p. 3 View in Reaxys Boreskow et al.; Zhurnal Fizicheskoi Khimii; vol. 28; (1954); p. 837; ; (1955); p. 6508 View in Reaxys Schwab et al.; Zeitschrift fuer Elektrochemie und Angewandte Physikalische Chemie; vol. 63; (1959); p. 461 View in Reaxys Toptschiewa et al.; ; vol. 9; (1957); p. 799 View in Reaxys Toptschiewa; Jun-Pin; Doklady Akademii Nauk SSSR; vol. 101; (1955); p. 305; ; (1956); p. 43 View in Reaxys Toptschiewa; Jun-Pin; Zhurnal Fizicheskoi Khimii; vol. 29; (1955); p. 1678,1854,2076; ; (1956); p. 7558,9123,9124 View in Reaxys Balandin et al.; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; (1958); p. 233;engl.Ausg.S.218 View in Reaxys Balaceanu; Jungers; ; vol. 60; (1951); p. 476,492,504 View in Reaxys Shimizu; Nippon Kagaku Zasshi; vol. 79; (1958); p. 291,297; ; (1958); p. 19334 View in Reaxys OH

aluminium oxide

Rx-ID: 7053576 View in Reaxys 340/630 Yield

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View in Reaxys Shimizu; Nippon Kagaku Zasshi; vol. 79; (1958); p. 291,297; ; (1958); p. 19334 View in Reaxys

P purple

Rx-ID: 26426618 View in Reaxys 341/630 Yield

Conditions & References

0 %, 0 %

Oppenheim, A.; Bulletin de la Societe Chimique de France; vol. 1; (1864); p. 163 - 165 View in Reaxys vol. P: MVol.B; 3.6.1, page 329 - 331 ; (from Gmelin) View in Reaxys

O N O O

HO O

HO OH

Rx-ID: 40411510 View in Reaxys 342/630 Yield

Conditions & References With Aeroxide P25 TiO2 in water, Irradiation, Catalytic behavior, Kinetics, Reagent/catalyst Boxi, Siddhartha Sankar; Paria, Santanu; RSC Advances; vol. 5; nb. 47; (2015); p. 37647 - 37668 View in Reaxys

O BrIMg

Rx-ID: 537317 View in Reaxys 343/630 Yield

Conditions & References T= 10 °C , Geschwindigkeit im Hochvakuum Meisenheimer; Piper; Lange; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 147; (1925); p. 343 View in Reaxys OH

Rx-ID: 1878295 View in Reaxys 344/630 Yield

Conditions & References With H3[PW12O40], T= 75 - 130 °C , further temperatures, Mechanism Okuhara, Toshio; Kasai, Atsushi; Hayakawa, Nobukiyo; Misono, Makoto; Yoneda, Yukio; Chemistry Letters; (1981); p. 391 - 394 View in Reaxys

Rx-ID: 2885240 View in Reaxys 345/630 Yield 43 % Chromat., 32 % Chromat., 19 % Chromat.,

Conditions & References With low-valent titanium, T= 300 °C , var. temp., Product distribution Malinowski, M.; Dams, R.; Geise, H.J.; Bulletin des Societes Chimiques Belges; vol. 94; nb. 2; (1985); p. 93 - 96 View in Reaxys

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5 % Chromat., 2 % Chromat. O C

O O

2H 2H

O 2H

O O

Rx-ID: 3989450 View in Reaxys 346/630 Yield

Conditions & References

3.0 % Chromat., 1.0 % Chromat., 7.0 % Chromat., 0.3 % Chromat.

With deuterium, Ru(acac)3, methyl iodide, 1.) 150 deg C, 4 h, 14 MPa, CO/D2=2.5; 2.) 170 deg C, 4 h, 10 MPa, CO/D2=2.5; 3.) 200 deg C, 6 h, 8 MPa, CO/D2=1.0; product distribution after successive steps, Product distribution Braca, G.; Galletti, A. M. Raspolli; Sbrana, G.; Lazzaroni, R.; Journal of Organometallic Chemistry; vol. 289; (1985); p. 107 - 116 View in Reaxys

nitrogen

Rx-ID: 5802856 View in Reaxys 347/630 Yield

Conditions & References T= 450 °C , Leiten ueber Thoriumoxyd Briner; Bron; Helvetica Chimica Acta; vol. 15; (1932); p. 1234,1240 View in Reaxys

O Si

CO2, H2O, H2, SiO2

Rx-ID: 6727218 View in Reaxys 348/630 Yield

Conditions & References With Titanium(IV) oxide, T= 132.9 - 458.9 °C , decomposition on TiO2 surface, Product distribution, Mechanism Jurgens; Rogers Jr.; Journal of physical chemistry; vol. 99; nb. 2; (1995); p. 731 - 743 View in Reaxys With water, Titanium(IV) oxide, T= 134.9 - 456.9 °C , decomposition on TiO2 surface, Product distribution, Mechanism Jurgens; Rogers Jr.; Journal of physical chemistry; vol. 99; nb. 2; (1995); p. 731 - 743 View in Reaxys O

H2O, H2, CO2 Rx-ID: 7076528 View in Reaxys 349/630

Yield

Conditions & References With Titanium(IV) oxide, T= 147.9 - 418.9 °C , decomposition on TiO2 surface, Product distribution Jurgens; Rogers Jr.; Journal of physical chemistry; vol. 99; nb. 2; (1995); p. 731 - 743 View in Reaxys

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-1 F (v4)

B FF

O+

usual alkylation products

Si F

Rx-ID: 8428220 View in Reaxys 350/630 Yield

Conditions & References

3.9 %, 2.9 %, 1.2 %, 0.02 %

With cesium fluoride, Product distribution, Mechanism Olah, George A.; Doggweiler, Hans; Felberg, Jeff D.; Journal of Organic Chemistry; vol. 49; nb. 12; (1984); p. 2112 - 2116 View in Reaxys

Rx-ID: 8832520 View in Reaxys 351/630 Yield

Conditions & References With MnAPO-46, Time= 5h, T= 350 °C , Product distribution, Further Variations: Catalysts, Temperatures Cheralathan; Kannan; Palanichamy; Murugesan; Indian Journal of Chemistry - Section A Inorganic, Physical, Theoretical and Analytical Chemistry; vol. 39; nb. 9; (2000); p. 921 - 927 View in Reaxys OH

O HO

Rx-ID: 40295686 View in Reaxys 352/630 Yield

Conditions & References

0.1 %, 1.1 %, 0.5 %, 6.2 %, 0.1 %, 0.1 %, 0.1 %

With carbonated carbonate-containing hydroxyapatites (HapNa-CO3), T= 350 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 9.5 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys

0.2 %, 2.0 %, 0.5 %, 2.9 %, 0.7 %, 0.03 %, 0.3 %

With carbonated carbonate-containing hydroxyapatites (HapE-Na-CO3), T= 350 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Overall yield = 6.8 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys

Si O

Rx-ID: 140451 View in Reaxys 353/630 Yield

Conditions & References T= 100 - 550 °C Frejka; Wiesner; Collection of Czechoslovak Chemical Communications; vol. 23; (1958); p. 1984 View in Reaxys

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O– Na +

Na + O–

Rx-ID: 281463 View in Reaxys 354/630 Yield

Conditions & References T= 160 °C Geuther; Schiele; Journal fuer Praktische Chemie (Leipzig); vol. <2> 4; (1871); p. 445 View in Reaxys Geuther; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1868); p. 513,658 View in Reaxys Geuther; Journal fuer Praktische Chemie (Leipzig); vol. <2> 4; (1871); p. 445 View in Reaxys

Rx-ID: 537391 View in Reaxys 355/630 Yield

Conditions & References T= 90 °C , im Hochvakuum v. Grosse; Chemische Berichte; vol. 59; (1926); p. 2651 View in Reaxys -1 I

O+

I (v3)

Rx-ID: 539862 View in Reaxys 356/630 Yield

Conditions & References T= 25 °C , langsam Meerwein et al.; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;154; (1940); p. 121; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;147; (1937); p. 274 View in Reaxys T= 50 - 60 °C , rasch Meerwein et al.; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;154; (1940); p. 121; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;147; (1937); p. 274 View in Reaxys

Rx-ID: 588556 View in Reaxys 357/630 Yield

Conditions & References T= 95 °C , unter vermindertem Durk Jolibois; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 155; (1912); p. 353 View in Reaxys

O P

O–

Na +

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O O

P O

Rx-ID: 844827 View in Reaxys 358/630 Yield

Conditions & References Rueggeberg; Chernack; Journal of the American Chemical Society; vol. 70; (1948); p. 1803 View in Reaxys

O C

Rx-ID: 2899774 View in Reaxys 359/630 Yield

Conditions & References

34 % Chromat., 25 % Chromat., 20 % Chromat., 10 % Chromat., 5 % Chromat., 1 % Chromat.

With low-valent titanium, T= 200 °C , var. temp., Product distribution Malinowski, M.; Dams, R.; Geise, H.J.; Bulletin des Societes Chimiques Belges; vol. 94; nb. 2; (1985); p. 93 - 96 View in Reaxys

O O

Al2O3

Rx-ID: 5853940 View in Reaxys 360/630 Yield

Conditions & References T= 80 - 90 °C Sigmund; Herschdoerfer; Monatshefte fuer Chemie; vol. 58; (1931); p. 285 View in Reaxys

O O

nickel

pumice stone

Rx-ID: 5853942 View in Reaxys 361/630 Yield

Conditions & References T= 250 - 260 °C , in Quarzroehre Staudinger; Rathsam; Helvetica Chimica Acta; vol. 5; (1922); p. 653 View in Reaxys

O O

Al2O3

O O

Rx-ID: 5854246 View in Reaxys 362/630 Yield

Conditions & References T= 75 °C Sigmund; Herschdoerfer; Monatshefte fuer Chemie; vol. 58; (1931); p. 285 View in Reaxys

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nickel pumice stone

Rx-ID: 6188340 View in Reaxys 363/630 Yield

Conditions & References T= 250 °C Staudinger; Rathsam; Helvetica Chimica Acta; vol. 5; (1922); p. 653 View in Reaxys

anhydrous FeCl3

C O Rx-ID: 6212205 View in Reaxys 364/630

Yield

Conditions & References T= 150 °C van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys OH

aqueous Al2O3

Rx-ID: 6918331 View in Reaxys 365/630 Yield

Conditions & References T= 250 °C Munro; Horn; Canadian Journal of Research; vol. 12; (1935); p. 707; Chem. Zentralbl.; vol. 106; nb. II; (1935); p. 1161 View in Reaxys O

SO2

Rx-ID: 7086554 View in Reaxys 366/630 Yield

Conditions & References T= 200 °C Prinz; Justus Liebigs Annalen der Chemie; vol. 223; (1884); p. 374 View in Reaxys

Rx-ID: 42442 View in Reaxys 367/630 Yield

Conditions & References T= 180 °C , beim Erhitzen des Hydrochlorids van Hove; Chem. Zentralbl.; vol. 78; nb. I; (1907); p. 235 View in Reaxys

Rx-ID: 101114 View in Reaxys 368/630 Yield

Conditions & References T= 200 °C , Explodiert heftig Askenasy; Meyer,V.; Chemische Berichte; vol. 25; (1892); p. 1703 View in Reaxys

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O S

Rx-ID: 141173 View in Reaxys 369/630 Yield

Conditions & References T= 150 °C Patent; Krafft; Roos; DE69115; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 3; p. 11 View in Reaxys Krafft; Roos; Chemische Berichte; vol. 26; (1893); p. 2826 View in Reaxys

Rx-ID: 190057 View in Reaxys 370/630 Yield

Conditions & References T= 200 °C Oda; Scientific Papers of the Institute of Physical and Chemical Research (Japan); vol. 22; (1933); p. 47,51; ; vol. 36; (1933); p. 331,334 View in Reaxys

Na +

S O

O–

Rx-ID: 193486 View in Reaxys 371/630 Yield

Conditions & References T= 150 °C , durch Erhitzen der wasserfreien Saeure im geschlossenen Rohr Krafft; Roos; Chemische Berichte; vol. 26; (1893); p. 2826 View in Reaxys O N

Rx-ID: 1462564 View in Reaxys 372/630 Yield

Conditions & References

33.2 %, 34.0 %, 32.8 %

Ambient temperature, Irradiation, Product distribution, Mechanism Olah, George A.; Doggweiler, Hans; Felberg, Jeff D.; Journal of Organic Chemistry; vol. 49; nb. 12; (1984); p. 2116 - 2120 View in Reaxys

HO 2

O OH

Rx-ID: 3554273 View in Reaxys 373/630 Yield

Conditions & References T= 25 - 60 °C , enthalpy of the guest-release reaction, ΔH, Thermodynamic data

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Barbour, Leonard J.; Caira, Mino R.; Nassimbeni, Luigi R.; Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999); nb. 8; (1993); p. 1413 - 1414 View in Reaxys O

hydrogen

iron

Rx-ID: 5803373 View in Reaxys 374/630 Yield

Conditions & References T= 90 - 170 °C , die Aetherbildung wird durch Gegenwart von 0.02-0.03prozent Sauerstoff verhindert Patent; Elektrizitaetswerk Lonza; DE317589; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 56 View in Reaxys O

hydrogen

nickel

Rx-ID: 5803374 View in Reaxys 375/630 Yield

hydrogen

platinum

Rx-ID: 5803375 View in Reaxys 376/630 Yield

ZnCl2

C O

Rx-ID: 6212249 View in Reaxys 377/630 Yield

Conditions & References T= 150 °C van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys

Al2O3

C O Rx-ID: 6212266 View in Reaxys 378/630

Yield

Conditions & References T= 200 - 250 °C Senderens; Bulletin de la Societe Chimique de France; vol. <4>5; (1909); p. 484; Annales de Chimie (Cachan, France); vol. <8>28; (1913); p. 303 View in Reaxys O

hydrogen

nickel

Rx-ID: 6672377 View in Reaxys 379/630 Yield

Conditions & References T= 210 °C Cabanac; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 188; (1929); p. 1258

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View in Reaxys O

O–

alcoholic potash

S O

O K+

Rx-ID: 6680389 View in Reaxys 380/630 Yield

Conditions & References T= 70 - 80 °C Nef; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 20 View in Reaxys O

O– Na +

ethylcarbonate sodium

Rx-ID: 6728210 View in Reaxys 381/630 Yield

Conditions & References T= 120 °C Geuther; ; (1868); p. 658 View in Reaxys O OH

N O

aluminium oxide

aluminium oxide silicon dioxide

O H

Rx-ID: 7053577 View in Reaxys 382/630 Yield

Conditions & References T= 350 - 450 °C Boreskow et al.; Zhurnal Fizicheskoi Khimii; vol. 27; (1953); p. 1172; ; (1954); p. 5627 View in Reaxys Antipina; Vestnik Moskovskogo Universiteta; vol. 13; nb. 2; (1958); p. 197; ; (1959); p. 6741 View in Reaxys Antipina; Isaew; Zhurnal Fizicheskoi Khimii; vol. 31; (1957); p. 2078 View in Reaxys OH

chloroammonium

NH 2 O

Rx-ID: 7057675 View in Reaxys 383/630 Yield

Conditions & References T= 260 - 400 °C Berthelot; Justus Liebigs Annalen der Chemie; vol. 83; (1852); p. 110 View in Reaxys

Cl Al

(C2H5+O)2 AlCl Rx-ID: 7070517 View in Reaxys 384/630

Yield

Conditions & References T= 100 °C Betse; ; vol. 6; p. 150; Chem. Zentralbl.; vol. 102; nb. II; (1931); p. 1692 View in Reaxys

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O– Na +

P O

sodium salt of ethylphosphonic acid monoethyl ester

Rx-ID: 7086863 View in Reaxys 385/630 Yield

Conditions & References T= 100 °C Janczak; Roczniki Chemii; vol. 6; (1926); p. 783 View in Reaxys Cl

<2BCl2(OC2H5)+(C2H5)2O>

Rx-ID: 8266255 View in Reaxys 386/630 Yield

Conditions & References T= -40 °C Wiberg; Suetterlin; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 202; (1931); p. 36 View in Reaxys

H2ptcl6

platinum

Rx-ID: 8285416 View in Reaxys 387/630 Yield

Conditions & References Gilman; Apperson; Journal of Organic Chemistry; vol. 4; (1939); p. 167 View in Reaxys O–

K+

SO2

Rx-ID: 8287131 View in Reaxys 388/630 Yield

Conditions & References T= 250 - 350 °C Claesson; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 19; (1879); p. 261 View in Reaxys Nef; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 48 View in Reaxys

2 – O– Cl

Sb5+

antimony (III)-chloride

Rx-ID: 8426048 View in Reaxys 389/630 Yield

Conditions & References T= 145 - 150 °C Dubrowina; Uchenye Zapiski, Kazanskii Gosudarstvennyi Universitet; vol. 116; nb. 2; (1956); p. 3,16,39; ; (1957); p. 6534 View in Reaxys

Rx-ID: 52231 View in Reaxys 390/630 Yield

Conditions & References T= 185 °C , Leiten ueber entwaesserten Alaun Mailhe; de Godon; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 170; (1920); p. 329; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;27; (1920); p. 121 View in Reaxys

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Mailhe; de Godon; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 27; (1920); p. 122; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 170; (1920); p. 330 View in Reaxys

N H

Rx-ID: 193512 View in Reaxys 391/630 Yield

Conditions & References T= 150 °C Swarts; Chem. Zentralbl.; vol. 75; nb. II; (1904); p. 1377 View in Reaxys O

O S

Rx-ID: 753388 View in Reaxys 392/630 Yield

Conditions & References T= 110 - 115 °C , bei der analogen Reaktion mit Propylalkohol,Butylalkohol oder Isopentylalkohol entstehen daneben auch Olefine Below; Lebedew; Zhurnal Obshchei Khimii; vol. 16; (1946); p. 669; ; (1947); p. 1205 View in Reaxys T= 110 - 115 °C Below; Lebedew; Zhurnal Obshchei Khimii; vol. 16; (1946); p. 669; ; (1947); p. 1205 View in Reaxys

S O

Rx-ID: 765142 View in Reaxys 393/630 Yield

Conditions & References T= 130 - 135 °C , im geschlossenen Rohr Krafft; Roos; Chemische Berichte; vol. 25; (1892); p. 2261; Chemische Berichte; vol. 26; (1893); p. 2825 View in Reaxys

Rx-ID: 846179 View in Reaxys 394/630 Yield

Conditions & References T= 80 °C Horner; Jurgeleit; Justus Liebigs Annalen der Chemie; vol. 591; (1955); p. 138,151 View in Reaxys

Fe Cl

Cl (v3)

O O

Rx-ID: 5802859 View in Reaxys 395/630 Yield

Conditions & References T= 150 °C , im Rohr

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van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys O

Cl Fe Cl

(v3)

C O Rx-ID: 6212248 View in Reaxys 396/630

Yield

Conditions & References T= 150 °C van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys Br

Rx-ID: 6672718 View in Reaxys 397/630 Yield

Conditions & References T= 200 °C Reynoso; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1856); p. 567 View in Reaxys O

S O

S OO

Rx-ID: 7046981 View in Reaxys 398/630 Yield

Conditions & References T= 140 °C Mayer,F.; Chemische Berichte; vol. 23; (1890); p. 909 View in Reaxys O

O S

C2H5OH

S OO

Rx-ID: 7046982 View in Reaxys 399/630 Yield

Conditions & References Kremann; Monatshefte fuer Chemie; vol. 31; (1910); p. 211,245, 275, 671 View in Reaxys Kailan; Monatshefte fuer Chemie; vol. 30; (1909); p. 2 View in Reaxys Zaitschek; Zeitschrift fuer Physikalische Chemie, Stoechiometrie und Verwandtschaftslehre; vol. 24; (1897); p. 1 View in Reaxys Villiers; Annales de Chimie (Cachan, France); vol. &lt;5&gt;21; (1880); p. 113; Annales de Chimie (Cachan, France); vol. &lt;7&gt;29; (1903); p. 561 View in Reaxys OH

aromatics of ethanol Rx-ID: 7069229 View in Reaxys 400/630

Yield

Conditions & References With zeolytes of diff. Al:Si ratio, Product distribution Novakova, Jana; Kubelkova, Ludmila; Habersberger, Karel; Dolejsek, Zdenek; Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases; vol. 80; (1984); p. 1457 - 1466 View in Reaxys

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S O

SO2

cymene Rx-ID: 7086658 View in Reaxys 401/630

Yield

Conditions & References T= 120 °C , im Einschlussrohr, dl-pinene Bruere; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 90; (1880); p. 1429; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1880); p. 444 View in Reaxys

F F

difluoroethylamine

tetrafluorodiethylamine

Rx-ID: 7087796 View in Reaxys 402/630 Yield

Conditions & References T= 150 - 170 °C Swarts; Chem. Zentralbl.; vol. 75; nb. II; (1904); p. 1377 View in Reaxys

O S

monosulfonic acid of methyl-diphenyl-amine

disulfonic acid of methyl-diphenyl-amine Rx-ID: 7455636 View in Reaxys 403/630

Yield

Conditions & References T= 150 °C Below; Finkel'schtein; Zhurnal Obshchei Khimii; vol. 16; (1946); p. 1248,1251; ; (1947); p. 3065 View in Reaxys

Cl Fe Cl

(v3)

FeCl2

Rx-ID: 8276216 View in Reaxys 404/630 Yield

Conditions & References Gilman; Apperson; Journal of Organic Chemistry; vol. 4; (1939); p. 167 View in Reaxys O OH

O I

S–

Na +

Rx-ID: 190636 View in Reaxys 405/630 Yield

Conditions & References T= 200 °C , im geschlossenen Rohr Otto; Engelhardt; Chemische Berichte; vol. 21; (1888); p. 654 View in Reaxys

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2 Br– 3

O–

Sb5+

Rx-ID: 628777 View in Reaxys 406/630 Yield

Conditions & References T= 130 - 135 °C Dubrowina; Uchenye Zapiski, Kazanskii Gosudarstvennyi Universitet; vol. 116; nb. 2; (1956); p. 3,16,39; ; (1957); p. 6534 View in Reaxys 2

O N

Rx-ID: 1896872 View in Reaxys 407/630 Yield

Conditions & References

17.9 %, 29.7 %, 15.2 %, 37.2 %

Ambient temperature, Irradiation, deuterium distribution, Product distribution, Mechanism Olah, George A.; Doggweiler, Hans; Felberg, Jeff D.; Journal of Organic Chemistry; vol. 49; nb. 12; (1984); p. 2116 - 2120 View in Reaxys

Cl Fe Cl

(v3)

O O

Rx-ID: 5853962 View in Reaxys 408/630 Yield

Conditions & References T= 150 °C van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys

Al2O3

H 2N

Rx-ID: 6046957 View in Reaxys 409/630 Yield

Conditions & References T= 240 - 280 °C , Kinetics Zoellner; Marton; Acta Chimica Academiae Scientiarum Hungaricae; vol. 13; (1958); p. 283,289; Acta Chimica Academiae Scientiarum Hungaricae; vol. 13; (1958); p. 283,287 View in Reaxys

O Fe

(v3)

Rx-ID: 6674603 View in Reaxys 410/630 Yield

Conditions & References T= 150 °C van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys OH

Rx-ID: 7057720 View in Reaxys 411/630 Yield

Conditions & References T= 80 °C , im Rohr Traube,J.; Neuberg,O.; Chemische Berichte; vol. 24; (1891); p. 520

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View in Reaxys

ethylmercury bromide

Rx-ID: 7059041 View in Reaxys 412/630 Yield

Conditions & References T= 150 °C , sowie bei 175grad; im Rohr Koton; Florinsski; Zhurnal Obshchei Khimii; vol. 9; (1939); p. 2198; Chem. Zentralbl.; vol. 111; nb. II; (1940); p. 334 View in Reaxys O

aluminium silicate OH

Rx-ID: 7066043 View in Reaxys 413/630 Yield

Conditions & References T= 150 - 500 °C , weitere Produkte: Kohlenmonoxid, Kohlendioxid und Kohlenwasserstoff, Kinetics Schuikin; Posdnjak; Sb. Statei Obshch. Khim.; (1953); p. 1008,1010; ; (1955); p. 6855 View in Reaxys OH

iodine-potassium iodide

KCl

Rx-ID: 7079337 View in Reaxys 414/630 Yield

Conditions & References T= 180 - 200 °C , Produkt5:C2H5I Hoeland; Justus Liebigs Annalen der Chemie; vol. 240; (1887); p. 241 View in Reaxys

O–

F F

S+

F F

O S

H O+ H

O–

different ethers, different salts, according to thesolvent used Rx-ID: 8450052 View in Reaxys 415/630

Yield

Conditions & References T= 25.4 °C , different solvents, different temperatures, Rate constant Kevill, Denis N.; Anderson, Steven W.; Journal of Heterocyclic Chemistry; vol. 25; (1988); p. 399 - 402 View in Reaxys

Rx-ID: 60825 View in Reaxys 416/630 Yield

Conditions & References T= 200 °C Rasuwaew; Sorokin; Zhurnal Obshchei Khimii; vol. 23; (1953); p. 1519; engl.Ausg.S.1589 View in Reaxys

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Cl Cl

Cl O

Rx-ID: 188641 View in Reaxys 417/630 Yield

Conditions & References T= 220 °C Rasuwaew; Sorokin; Zhurnal Obshchei Khimii; 23&gt;1953&gt;1519;engl.Ausg.S.1589 View in Reaxys

Rx-ID: 1878343 View in Reaxys 418/630 Yield

Conditions & References With molecular sieve, water, oxygen, other catalysts; oxidative dehydrogenation, Product distribution Rao, P. R. Hari Prasad; Thangaraj, A.; Ramaswamy, A. V.; Journal of the Chemical Society, Chemical Communications; nb. 16; (1991); p. 1139 - 1140 View in Reaxys

Rx-ID: 28499303 View in Reaxys 419/630 Yield

Conditions & References With hydroxyapatite with 1.62 Ca/P molar ratio, T= 46.84 °C , Reactivity, Reagent/catalyst, Temperature Tsuchida, Takashi; Kubo, Jun; Yoshioka, Tetsuya; Sakuma, Shuji; Takeguchi, Tatsuya; Ueda, Wataru; Journal of Catalysis; vol. 259; nb. 2; (2008); p. 183 - 189 View in Reaxys OH

Rx-ID: 40291063 View in Reaxys 420/630 Yield

Conditions & References With Li0.9Zr2P2.9Mo0.1O12, Heating, Catalytic behavior, Reagent/catalyst Il'in; Ermilova; Orekhova; Yaroslavtsev; Inorganic Materials; vol. 51; nb. 7; (2015); p. 711 - 717; Neoorg. Mater.; vol. 51; nb. 7; (2015); p. 778 - 784 View in Reaxys

16 H H O -1

H+ I

I Bi

(v4)

Rx-ID: 545479 View in Reaxys 421/630 Yield

Conditions & References Auger; Ivanoff; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 202; (1936); p. 484 View in Reaxys

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2016-05-04 01:50:52

Rx-ID: 5802855 View in Reaxys 422/630 Yield

Conditions & References Niederist; Justus Liebigs Annalen der Chemie; vol. 186; (1877); p. 391 View in Reaxys Reynoso; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1856); p. 567 View in Reaxys O

phosphorus pentoxide

Rx-ID: 6188341 View in Reaxys 423/630 Yield

Conditions & References Staudinger; Rathsam; Helvetica Chimica Acta; vol. 5; (1922); p. 653 View in Reaxys I

tungsten acidic silver

AgI

WoO3

Rx-ID: 6221089 View in Reaxys 424/630 Yield

Conditions & References Goessmann; Justus Liebigs Annalen der Chemie; vol. 101; (1857); p. 218 View in Reaxys OH

OH HO

S OO

Rx-ID: 6918328 View in Reaxys 425/630 Yield

Conditions & References van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 758,761 View in Reaxys Senderens; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 49; (1931); p. 1146 View in Reaxys Cl

alcoholic alkali

Rx-ID: 6918330 View in Reaxys 426/630 Yield

Conditions & References Ismailski; Popow; Bulletin de la Societe Chimique de France; vol. &lt;5&gt;3; (1936); p. 2034; Zhurnal Obshchei Khimii; vol. 7; (1937); p. 111 View in Reaxys

oxide of heavy metal

Rx-ID: 6918334 View in Reaxys 427/630 Yield

Conditions & References Kretow; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 61; (1929); p. 2364; Chem. Zentralbl.; vol. 101; nb. II; (1930); p. 370 View in Reaxys

alcoholic alkali

O O

alkali nitrite

alkali nitrate Rx-ID: 7068593 View in Reaxys 428/630

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Yield

Conditions & References Nef; Justus Liebigs Annalen der Chemie; vol. 309; (1899); p. 136;; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 6 View in Reaxys Carlson; Chem. Zentralbl.; vol. 79; nb. I; (1908); p. 934 View in Reaxys

Br O

Rx-ID: 7978857 View in Reaxys 429/630 Yield

Conditions & References Blaise; Bulletin de la Societe Chimique de France; vol. <3> 35; (1906); p. 92 View in Reaxys Ahrens; Stapler; Chemische Berichte; vol. 38; (1905); p. 3266 View in Reaxys Ahrens; Stapler; Chemische Berichte; vol. 38; (1905); p. 1296;; Chemisches Zentralblatt; (1906); p. I,510 View in Reaxys Rx-ID: 40295684 View in Reaxys 430/630

Yield

Conditions & References With deficient carbonate-containing hydroxyapatites (HapD), T= 300 - 400 °C , Inert atmosphere, Guerbet Reaction, Catalytic behavior, Reagent/catalyst, Temperature, Overall yield = 14 percent Silvester, Lishil; Lamonier, Jean-Franois; Faye, Jrmy; Capron, Mickal; Vannier, Rose-Nolle; Lamonier, Carole; Dubois, Jean-Luc; Couturier, Jean-Luc; Calais, Christophe; Dumeignil, Franck; Catalysis Science and Technology; vol. 5; nb. 5; (2015); p. 2994 - 3006 View in Reaxys O

S O

O S

Rx-ID: 102247 View in Reaxys 431/630 Yield

Conditions & References Erlenmeyer,E.; Justus Liebigs Annalen der Chemie; vol. 162; (1872); p. 379 View in Reaxys Claesson; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 19; (1879); p. 259 View in Reaxys

O I2Mg

Rx-ID: 173049 View in Reaxys 432/630 Yield

Conditions & References Blaise; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 139; (1904); p. 1211 View in Reaxys

O I2Mg

Rx-ID: 174976 View in Reaxys 433/630 Yield

Conditions & References Blaise; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 139; (1904); p. 1211 View in Reaxys

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2016-05-04 01:50:52

Rx-ID: 188406 View in Reaxys 434/630 Yield

Conditions & References Mailhe; de Godon; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 27; (1920); p. 124 View in Reaxys aehnlich verlaufen die Reaktionen mit Propylalkohol, Isoamylalkohol und Allylalkohol Mailhe; de Godon; Bulletin de la Societe Chimique de France; vol. &lt;4&gt; 27; (1920); p. 123-126, 329 View in Reaxys

O I2Mg

Rx-ID: 212675 View in Reaxys 435/630 Yield

Conditions & References Blaise; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 139; (1904); p. 1211 View in Reaxys O O

Rx-ID: 624751 View in Reaxys 436/630 Yield

Conditions & References Patent; Hercules Powder Co.; US2136011; (1936) View in Reaxys Patent; Hercules Powder Co.; FR818787 View in Reaxys

O I2Mg

Rx-ID: 646717 View in Reaxys 437/630 Yield

Conditions & References Blaise; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 139; (1904); p. 1211 View in Reaxys N O O

H C–

P N

P+

Rx-ID: 1906578 View in Reaxys 438/630 Yield 26 % Spectr., 13 % Spectr., 8%

Conditions & References in benzene-d6, Time= 72h, Ambient temperature, in a sealed tube, Product distribution Beer, Paul D.; Edwards, Robert C.; Hall, C. Dennis; Jennings, J. R.; Cozens, R. J.; Phosphorus and Sulfur and the Related Elements; vol. 17; (1983); p. 283 - 296 View in Reaxys

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Spectr., 14 % Spectr. I

alcoholic potash

Rx-ID: 5803827 View in Reaxys 439/630 Yield

Conditions & References Lieben; Rossi; Justus Liebigs Annalen der Chemie; vol. 158; (1871); p. 170 View in Reaxys

O– Na +

p-toluenesulfonate of sodium

Rx-ID: 6219096 View in Reaxys 440/630 Yield

Conditions & References Ferns; Lapworth; Journal of the Chemical Society; vol. 101; (1912); p. 284 View in Reaxys Br

alcoholic potash

Rx-ID: 6672719 View in Reaxys 441/630 Yield

Conditions & References Nef; Justus Liebigs Annalen der Chemie; vol. 319; (1901); p. 130 View in Reaxys OH

OH HO

S OO

Rx-ID: 6945960 View in Reaxys 442/630 Yield

Conditions & References Moser; Lindinger; Monatshefte fuer Chemie; vol. 44; (1923); p. 142 View in Reaxys OH

kaolin

Rx-ID: 6945962 View in Reaxys 443/630 Yield

Conditions & References Skaerblom; Svensk Kemisk Tidskrift; vol. 40; p. 123; Chem. Zentralbl.; vol. 99; nb. II; (1928); p. 182 View in Reaxys OH

phosphorus pentoxide

Rx-ID: 6945963 View in Reaxys 444/630 Yield

Conditions & References Balarew; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 104; (1922); p. 368 View in Reaxys O

O S

(C2H5O)2SO2 Rx-ID: 7070546 View in Reaxys 445/630

Yield

Conditions & References Claesson; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 19; (1879); p. 240 View in Reaxys Willcox; American Chemical Journal; vol. 32; (1904); p. 468 View in Reaxys

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2016-05-04 01:50:52

Bushong; American Chemical Journal; vol. 32; (1904); p. 450 View in Reaxys O

O– Na +

Na2SO3

Rx-ID: 7081956 View in Reaxys 446/630 Yield

Conditions & References Janczak; Roczniki Chemii; vol. 10; p. 117,148; Chem. Zentralbl.; vol. 101; nb. I; (1930); p. 2869 View in Reaxys

O– Na +

NaNO3

Rx-ID: 7082039 View in Reaxys 447/630 Yield

Conditions & References Janczak; Roczniki Chemii; vol. 10; p. 140,141; Chem. Zentralbl.; vol. 101; nb. I; (1930); p. 2869 View in Reaxys O

O S F

sodium

sodium trifluoromethanesulfonate

Rx-ID: 7086949 View in Reaxys 448/630 Yield

Conditions & References Gramstad; Haszeldine; Journal of the Chemical Society; (1956); p. 173,176 View in Reaxys -1

F (v4)

B FF

aqueous Na2CO3

O+

Rx-ID: 7978583 View in Reaxys 449/630 Yield

Conditions & References Meerwein et al.; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;147; (1937); p. 268; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;154; (1940); p. 111,130,131 View in Reaxys

Br SbBr Br

Rx-ID: 8213736 View in Reaxys 450/630 Yield

Conditions & References beim Aufbewahren Raynaud; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;27; (1920); p. 411 View in Reaxys O

2 Cl

Sn ClCl

Rx-ID: 8240709 View in Reaxys 451/630 Yield

Conditions & References Zonew; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 48; (1916); p. 567; Chem. Zentralbl.; vol. 94; nb. I; (1923); p. 1497 View in Reaxys

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Br OH

O O

5.8-dibromo-naphthalene-sulfonic acid-(2)

S O

Rx-ID: 8254828 View in Reaxys 452/630 Yield

Conditions & References beim Erhitzen im geschlossenen Rohr Krafft; Roos; Chemische Berichte; vol. 26; (1893); p. 2826 View in Reaxys -1

I (v4)

Bi I I

I O

O+

triethyloxonium-heptaiodo dibismuthate

Rx-ID: 8289625 View in Reaxys 453/630 Yield

Conditions & References Meerwein et al.; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;154; (1940); p. 121; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt;147; (1937); p. 274 View in Reaxys

O O S

O O

O S

Rx-ID: 185153 View in Reaxys 454/630 Yield

Conditions & References Bauer; Jenkins; Journal of the American Pharmaceutical Association (1912-1977); vol. 26; (1937); p. 486; Chem. Zentralbl.; vol. 109; nb. I; (1938); p. 55 View in Reaxys

OH O O OH

O S

O O

Rx-ID: 193308 View in Reaxys 455/630 Yield

Conditions & References Jackson; Wing; American Chemical Journal; vol. 9; (1887); p. 354 View in Reaxys

Mg Br

Rx-ID: 441550 View in Reaxys 456/630 Yield

Conditions & References Kinetics Vavon; Barbier; Thiebaut; Bulletin de la Societe Chimique de France; vol. <5> 1; (1934); p. 806,812 View in Reaxys

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O S

Rx-ID: 783677 View in Reaxys 457/630 Yield

Conditions & References Krafft; Chemische Berichte; vol. 26; (1893); p. 2833 View in Reaxys

(v1)

-2

2 Ag+ (v1)

S OO

O S

Rx-ID: 5802860 View in Reaxys 458/630 Yield

Conditions & References Nef; Justus Liebigs Annalen der Chemie; vol. 309; (1899); p. 136;; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 6 View in Reaxys

O Ag+

O–

Rx-ID: 5803107 View in Reaxys 459/630 Yield

Conditions & References Chiminello; Gazzetta Chimica Italiana; vol. 25; (1895); p. II,410 View in Reaxys Nef; Justus Liebigs Annalen der Chemie; vol. 309; (1899); p. 136;; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 6 View in Reaxys O

Cl Fe Cl

(v3)

Rx-ID: 6188339 View in Reaxys 460/630 Yield

Conditions & References van Alphen; Recueil des Travaux Chimiques des Pays-Bas; vol. 49; (1930); p. 498 View in Reaxys

Al2O3

C O Rx-ID: 6212267 View in Reaxys 461/630

Yield

Conditions & References Senderens; Bulletin de la Societe Chimique de France; vol. <4>5; (1909); p. 484; Annales de Chimie (Cachan, France); vol. <8>28; (1913); p. 303 View in Reaxys

Cl Al

Si O

Rx-ID: 6672777 View in Reaxys 462/630 Yield

Conditions & References Stokes; American Chemical Journal; vol. 14; (1892); p. 444 View in Reaxys OH HO

S OO

Rx-ID: 6931648 View in Reaxys 463/630

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Yield

Conditions & References bei verschiedenen Temperaturen und Drucken Patent; Air Reduction Co.; DE767635; (1932); View in Reaxys Patent; Distiller Co.; DE596819; (1931); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 21; p. 81 View in Reaxys O

S O

C2H5OSO3H Rx-ID: 7070557 View in Reaxys 464/630

Yield

Conditions & References Produkt 5: H2SO4 Claesson; Journal fuer Praktische Chemie (Leipzig); vol. &lt;2&gt; 19; (1879); p. 240 View in Reaxys Mueller; Chemische Berichte; vol. 6; (1873); p. 228 View in Reaxys

diethyl ether of l-methylvinylcarbinol

diethyl ether of d-methylvinylcarbinol Rx-ID: 7074087 View in Reaxys 465/630

Yield

Conditions & References Prevost; Annales de Chimie (Cachan, France); vol. &lt;10&gt;10; (1928); p. 178,179; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 183; (1926); p. 744 View in Reaxys N

rhodanuracetic acid ester Rx-ID: 7086004 View in Reaxys 466/630

Yield

Conditions & References bei wiederholtem Destillieren; Produkt 9-10:Thiodiglykolsaeure,Thiodiglykolsaeureester,Acetylrhodanid,Cyansulfid,Aethylcarbylamin,Propionitril Klason; Chemische Berichte; vol. 14; (1881); p. 732 View in Reaxys

O Si

Cl Si O

silicon (IV)-chloride

Si O

Rx-ID: 7086420 View in Reaxys 467/630 Yield

Conditions & References bei Kochen; Prod.5: Hexaaethoxydisiloxan Wolnow; Zhurnal Obshchei Khimii; vol. 17; (1947); p. 1428,1433; ; (1948); p. 2230 View in Reaxys

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Na +

H –N

2-ethynyl-borneol

Rx-ID: 7443901 View in Reaxys 468/630 Yield

Conditions & References Barbe; ; (1929); p. 247; Chem. Zentralbl.; vol. 100; nb. II; (1929); p. 2774 View in Reaxys N OH

O O

benzamide-o-sulfonic acid

S Cl

Rx-ID: 7921458 View in Reaxys 469/630 Yield

Conditions & References Jesurun; Chemische Berichte; vol. 26; (1893); p. 2292 View in Reaxys -1 Cl (v4)

Al ClCl

O+

Rx-ID: 7978882 View in Reaxys 470/630 Yield

aqueous alkaline solution

Rx-ID: 7978883 View in Reaxys 471/630 Yield

OH HO

S OO

Rx-ID: 7987367 View in Reaxys 472/630 Yield

Conditions & References Klages; Chemische Berichte; vol. 35; (1902); p. 2649; Chemische Berichte; vol. 39; (1906); p. 2591 View in Reaxys

Cl Cl

B F

F O

Rx-ID: 8211647 View in Reaxys 473/630

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Yield

2 Cl

Sn ClCl

Rx-ID: 8240710 View in Reaxys 474/630 Yield

Conditions & References bei hoeherer Temperatur Zonew; Zhurnal Russkago Fiziko-Khimicheskago Obshchestva; vol. 48; (1916); p. 567; Chem. Zentralbl.; vol. 94; nb. I; (1923); p. 1497 View in Reaxys

N+

I–

platinum

Rx-ID: 8240933 View in Reaxys 475/630 Yield

Conditions & References Hydrogenation Arens et al.; Recueil des Travaux Chimiques des Pays-Bas; vol. 74; (1955); p. 1040,1043 View in Reaxys

Rx-ID: 57377 View in Reaxys 476/630 Yield

Conditions & References Mailhe; de Godon; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 170; (1920); p. 329; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;27; (1920); p. 121 View in Reaxys

(v2)

Rx-ID: 176871 View in Reaxys 477/630 Yield

Conditions & References Paterno; Justus Liebigs Annalen der Chemie; vol. 150; (1869); p. 134 View in Reaxys -1 Cl (v4)

Al ClCl

N O

O+

Rx-ID: 266988 View in Reaxys 478/630 Yield

Rx-ID: 693267 View in Reaxys 479/630

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Yield

Conditions & References Mailhe; de Godon; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;27; (1920); p. 329 View in Reaxys O

O O

Rx-ID: 729527 View in Reaxys 480/630 Yield

Conditions & References unter gewoenlichem Druck Krafft; Roos; Chemische Berichte; vol. 26; (1893); p. 2826 View in Reaxys

ThO2

Rx-ID: 5803832 View in Reaxys 481/630 Yield

Conditions & References Produkt5:CO Produkt6:CO2 Sabatier; Mailhe; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 154; (1912); p. 51 View in Reaxys OH

propylmercury bromide O

Rx-ID: 7059042 View in Reaxys 482/630 Yield

Conditions & References Koton; Florinsski; Zhurnal Obshchei Khimii; vol. 9; (1939); p. 2198; Chem. Zentralbl.; vol. 111; nb. II; (1940); p. 334 View in Reaxys

(v2)

ZnCl2

Rx-ID: 7089332 View in Reaxys 483/630 Yield

Conditions & References Produkt5: ZnO Paterno; Justus Liebigs Annalen der Chemie; vol. 150; (1869); p. 134 View in Reaxys

Cl (v3)

(v3)

Rx-ID: 8240632 View in Reaxys 484/630 Yield

Conditions & References Ducelliez; Raynaud; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 158; (1914); p. 577; Bulletin de la Societe Chimique de France; vol. &lt;4&gt;15; (1914); p. 413 View in Reaxys O OH

S O

O S

O S OH

OH O O

O S OH

Rx-ID: 189319 View in Reaxys 485/630

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Yield

Conditions & References Kohler; American Chemical Journal; vol. 19; (1897); p. 737; American Chemical Journal; vol. 20; (1898); p. 680 View in Reaxys

zinc

Rx-ID: 7058032 View in Reaxys 486/630 Yield

Conditions & References Wislicenus; Justus Liebigs Annalen der Chemie; vol. 226; (1884); p. 270 View in Reaxys O OH

O N–

K+

KBr

Rx-ID: 8278596 View in Reaxys 487/630 Yield

Conditions & References Loessner; Journal fuer Praktische Chemie (Leipzig); vol. <2> 10; (1874); p. 254 View in Reaxys

Rx-ID: 6918327 View in Reaxys 488/630 Yield 100%

Conditions & References 122.3 : Step 3 Step 3 Trifluoroacetic acid (1.0 mL, 12.78 mmol) was added to a stirred solution of the alcohol (0.221 g, 0.97 mmol) in CH2 Cl2 (5.0 mL) and the mixture stirred at room temperature for 2 hours. The solvent was removed in vacuo giving a syrup which solidified from Et2 O/n-hexane. This gave the product as a white solid (0.236 g, 100percent) which was used directly without further purification. Patent; Warner-Lambert Company; US5593967; (1997); (A1) English View in Reaxys

99%

1 : (1) The mixture was heated at 55° C. for 12 hours, and the reaction solution was concentrated to a smaller volume and admixed with a volume of ethyl ether. The precipitate as deposited was removed by filtration and well washed with ethyl ether to give 1.2 g of the titled compound as a colorless solid. Yield 99percent. [α]D 23 +130° (c=0.2, acetone) Elemental Analysis: Found: C 51.96, H.5.26, N 8.37, S 11.92percent; Calcd. for C57 H68 N8 O18 S5:C 52.12, H 5.22, N 8.53, S 12.20percent Patent; Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; US4357466; (1982); (A1) English View in Reaxys

97.4%

Preparation of MPEG-Cl 750 and MPEG-Cl 5000 Preparation of MPEG-Cl 750 and MPEG-Cl 5000 MPEG 750 (25.68 g, 34.24 mmoles) was dried by distillation from toluene in vacuo. Following addition of 95 ml (1.302 moles) of freshly distilled thionyl chloride the reaction was refluxed for 9 hr. under nitrogen. Excess thionyl chloride was removed by vacuum distillation. The yellow residue was dissolved in 50 ml of chloroform, filtered, and precipitated with 500 ml of ethyl ether at -20° C. or 4° C. for MPEG-Cl 5000. The product was recrystallized twice from chloroform/ethyl ether and dried under vacuum; yield 12.72 g. (48.3percent), (97.4percent yield from MPEG-5000); i.r. (neat) 663 cm-1 (C-Cl), no absorption for OH at 3473 cm-1. Size exclusion chromatography of MPEG-Cl 5000 (1.5 ml/min., 0.05M potassium phosphate) showed no change in molecular weight relative to the starting material.

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Patent; Baxter Biotech Technology Sarl; US5907035; (1999); (A1) English View in Reaxys 95%

1 : Diphenylmethyl 6,6-dibromopenicillanate STR11 6,6-Dibromopenicillanic acid (90 g) in acetonitrile (450 ml) was treated with a solution of diphenyldiazomethane (49 g) in the same solvent (150 ml). After 1 hour at 20° C. the formed solid was collected by filtration and washed with small portions of cold ethyl ether, thus obtaining 116 g of title product. A second crop (9 g) was obtained by evaporation of the mother liquors and trituration with ethyl ether; yield 95percent. An analytical sample was obtained by crystallization from chloroform; mp 157°-158°; γmax (CHCl3 film) 1800, 1750 cm-1; δ (CDCl3) 1.24 and 1.58 (each 3H, s, CMe2), 4.61 (1H, s, N.CH.CO), 5.80 (1H, s, N.CH.S), 6.91 (1H, s, OCH), and 7.30 ppm (10H, s, Ar). Found: C, 47.80; H, 3.63; N, 2.64; S, 5.95; Br, 30.49percent. C21 H19 Br2 NO3 S requires C, 48.02; H, 3.64; N, 2.67; S, 6.10; Br, 30.43percent. Patent; Farmitalia Carlo Erba S.p.A.; US4585874; (1986); (A1) English View in Reaxys

92%

3 : Step 1 Step 3: Preparation of di-quaternary salt The mono-quaternary salt (0.933 g, 1.29 mmol, obtained from Step 2), iodoethane (0.300 mL/3.75 mmol), and acetonitrile (30.0 mL) were combined in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer, and heated to 50° C. After 24 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give a yellow foamy solid (1.166 g). The solid was dissolved in methylene chloride/acetonitrile and precipitated with ethyl ether. After cooling to 0° C. overnight, the resulting solid was filtered, washed with ethyl ether and concentrated in vacuo to yield the di-quaternary salt as an off-white solid (1.046 g, 92percent): 1 H NMR (CD3 OD) δ 0.59 (t, 6H), 0.70-1.10 (m, 9H), 1.16 (t, 3H), 1.22-1.80 (m, 9H), 2.42 (s, 6H), 2.78 (d, 2H), 2.98 (s, 6H), 3.02 (s, 6H), 3.22-3.37 (m, 4H), 3.63-3.78 (m, 4H), 3.80 (s, 4H), 4.93 (s, 1H), 5.71 (s, 1H), 6.22 (dd, 1H), 6.61 (d, 2H), 7.02 (d, 2H), 7.40 (d, 1H). Patent; G.D. Searle and Company; US6107494; (2000); (A1) English View in Reaxys

92%

3 : Step 3 Step 3 Preparation of Di-Quaternary Salt The mono-quaternary salt (0.933 g, 1.29 mmol, obtained from Step 2), iodoethane (0.300 mL/3.75 mmol), and acetonitrile (30.0 mL) were combined in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer, and heated to 50° C. After 24 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give a yellow foamy solid (1.166 g). The solid was dissolved in methylene chloride/acetonitrile and precipitated with ethyl ether. After cooling to 0° C. overnight, the resulting solid was filtered, washed with ethyl ether and concentrated in vacuo to yield the di-quaternary salt as an off-white solid (1.046 g, 92percent): 1 H NMR (CD3 OD) δ 0.59 (t, 6H), 0.70-1.10 (m, 9H), 1.16 (t, 3H), 1.22-1.80 (m, 9H), 2.42 (s, 6H), 2.78 (d, 2H), 2.98 (s, 6H), 3.02 (s, 6H), 3.22-3.37 (m, 4H), 3.63-3.78 (m, 4H), 3.80 (s, 4H), 4.93 (s, 1H), 5.71 (s, 1H), 6.22 (dd, 1H), 6.61 (d, 2H), 7.02 (d, 2H), 7.40 (d, 1H). Patent; G.D. Searle and Company; US5994391; (1999); (A1) English View in Reaxys

90%

1.c : EXAMPLE 1 1c) H-γ-O-Bzl-Glu-Gly-OH.TFA Molecular weight=408.4 9 ml TFA is added to 10 mmol α-Boc-γ-O-Bzl-Glu-Gly-OH (1b) dissolved in 20 ml methylenchloride. The mixture is stirred for 30 minutes at room temperature, evaporated in vacuo to an oil and precipitated with diethylether. Yield: 90percent Patent; Chromonogenix AB; US5334703; (1994); (A1) English

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View in Reaxys 86%

2.b : α-Ac-Ile-Ser-Gly-Lys-pNA.HCl Molecular weight=602.11 2b) α-Boc-O-Bzl-Ser-Gly-ε-Z-Lys,pNA Molecular weight=734.2 10 ml TFA is added to 5 mmol α-Boc-Gly-ε-Z-Lys-pNA (2a) dissolved in 20 ml methylenchloride. The mixture is stirred for 30 minutes at room temperature and the substance is precipitated with diethyleter. The dry substance is dissolved in 25 ml DMF and neutralized in cold (-10° C.) with Et3 N. To the solution 5 mmol α-Boc-O-Bzl-Ser-OH, 5 mmol HOBT and 5.1 mmol DCCl are added. The mixture is stirred for 1 hour in cold and overnight at room temperature. The formed DCU is filtered off and the solution is evaporated in vacuo to an oil which is dissolved in EtOAc and washed with 2percent NaHCO3, 2percent KHSO4 and H2 O. After drying with Na2 SO4 the EtOAc phase is evaporated and the substance is precipitated with diethylether as an oil which solidifies in vacuo. Yield: 86percent Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys

85%

61 : Recrystallization: ethyl ether Recrystallization: ethyl ether Yield: 85percent Melting point: 94° C. Patent; Adir et Compagnie; US5332735; (1994); (A1) English View in Reaxys

80.2%

Preparation of MPEG-IDA 750 and MPEG-IDA 5000 Preparation of MPEG-IDA 750 and MPEG-IDA 5000 MPEG-IDA 750 was prepared by reaction of MPEG-Cl 750 (1.00 g, 1.301 mmoles) with IDA (0.868 g, 6.52 mmoles) and potassium carbonate (2.70 g, 19.53 mmoles) in 35 ml of water for 24 hours at reflux (90°-95° C.). The reaction mixture was adjusted to pH 3.0 with concentrated HCl and extracted with 100 ml of 40/60 (v/v) chloroform/ethanol. The extract was concentrated, dried with anhydrous K2 CO3, filtered, and precipitated with ethyl ether at -20° C. (4° C. for MPEG-IDA 5000). The product was recrystallized twice from 40/60 chloroform/ethanol and ether and dried under vacuum; yield 0.39 g. (34.5percent), (80.2percent yield from MPEG-Cl 5000); i.r. (neat) 1729 cm-1, 1640 cm-1 (CO), no absorption for CCl at 663 cm-1. Ion exchange chromatography of the MPEG-IDA 5000 (0.5 mi/min., 0.01M Tris, pH 8) showed 81percent reaction completion. Patent; Baxter Biotech Technology Sarl; US5907035; (1999); (A1) English View in Reaxys

80%

56 : EXAMPLE 56 EXAMPLE 56 A mixture of 281 mg of 2-[2-(5-methylthienyl)]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one Ic1 -1, 5 ml of trifluoroacetic acid, and 96 mg of methanesulfonic acid is stirred at room temperature for 1.5 hours and dried up under reduced pressure. The resulting residue is mixed with ethyl ether and collected by filtration to give 300 mg (yield: 80percent) of the compound Ic1 -1as methanesulfonate. m.p.: 230°-234° C.(d). Anal. Calcd. (percent) (for C16 H15 N3 O4 S2.1/2H 2 O): C, 49.72; H, 4.17; N, 10.87. Found (percent): C, 49.72; H, 4.16; N, 10.88. Patent; Shionogi and Co., Ltd; US4690930; (1987); (A1) English View in Reaxys

73%

2.a : α-Ac-Ile-Ser-Gly-Lys-pNA.HCl Molecular weight=602.11 2a) α-Boc-Gly-ε-Z-Lys-pNA Molecular weight=557.6 5 mmol ε-Z-Lys-pNA.TFA (prepared as described in example 1a) dissolved in 25 ml DMF is neutralized in cold (-10° C.) with Et3 N.

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To the solution 5 mmol α-Boc-Gly-OH, 5 mmol HOBT and 5 mmol DCCl are added. The mixture is stirred for 1 hour in cold and overnight at room temperature. The formed DCU is filtered off and the solution is evaporated in vacuo to an oil which is dissolved in EtOAc and washed with 2percent NaHCO3, 2percent KHSO4 and H2 O. After drying with Na2 SO4 the EtOAc phase is evaporated in vacuo and the substance is precipitated with diethylether as an oil which solidifies in vacuo. Yield: 73percent Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys 72%

P.88 : Preparative Example 88 Preparative Example 88 A mixture of (S)-(+)-3-methyl-2-butylamine (3.0 g), 3,4-diethoxy-3-cyclobutene-1,2-dione (5 g) and absolute EtOH (100 mL) was stirred at 0-25° C. for 12 hrs. Filtration and concentration of the filtrate gave a syrup which solidified upon dilution with Et2O. Trituration of the solid with diethyl ether gave the desired product as a solid (4.4 g, 72percent, MH+=212). Patent; Taveras, Arthur G.; Aki, Cynthia J.; Bond, Richard W.; Chao, Jianping; Dwyer, Michael; Ferreira, Johan A.; Chao, Jianhua; Yu, Younong; Baldwin, John J.; Kaiser, Bernd; Li, Ge; Merritt, J. Robert; Nelson JR., Kingsley H.; Rokosz, Laura L.; US2004/97547; (2004); (A1) English View in Reaxys

72%

13 : Conjugation of Random H-(Ptyn)4(EOZ)20-T-NH2 and Irinotecan Azido Hexanoate H-(Ptyn)4(EOZ)20-T-NH2 (0.05 g, 0.0163 mmol, 1 eq., Mn 3070 Da), from a previous example, and irinotecan azido hexanoate (0.0473 g, 0.0652 mmol, 4 eq) were dissolved in water (2 mL). Sodium ascorbate (0.0013 g, 0.00652 mmol, 0.4 eq) and CuSO4.5H2O (0.0008 g, 0.00326 mmol, 0.2 eq) were added at room temperature. After stirring for 22 hours, water was removed using a rotary evaporator. The residue was dissolved in dichloromethane and then precipitated by addition to diethyl ether. Diethyl ether solution was decanted and the residue was dried in vacuo to give 0.7 g of the desired product as an offwhite powder (72percent yield). The 'click' coupling of the azide group (on irinotecan azido hexanoate) to the acetylene pendants (on POZ) was verified by NMR. 1H NMR (Varian, 500 MHz, 10 mg/mL CDCl3) shows that the polymer chain contained an average of 4 units of irinotecans with the aromatic proton peaks of irinotecan at 7.14 ppm (t, 1H), 7.57 ppm (br s, 1H), and 7.85 ppm (br s, 1H), 8.16 ppm (br s, 1H), and new signals at 4.27 ppm (br s, 2H, adjacent to triazole -CH2NR) and 7.40 ppm (br s, 1H, triazole). GPC gave Mn=4160 Da and Mp=4900 Da with PDI of 1.19. Patent; Serina Therapeutics, Inc.; US2010/330023; (2010); (A1) English View in Reaxys

70%

59 : Recrystallization: ethyl ether Recrystallization: ethyl ether Yield: 70percent Melting point: 78° C. Patent; Adir et Compagnie; US5332735; (1994); (A1) English View in Reaxys

70%

l.e : Step e Step e The product from step d (0.92 g) was stirred and refluxed in dry toluene (35 ml) for l5 minutes and then cooled until solid material began to precipitate out of the solution. 50percent sodium hydride (0.l5 g) was then added with stirring and the mixture stirred under reflux for a further l hour. After cooling, L-ethyl lactate mesylate (0.63 g) was added and the reaction mixture stirred under reflux for 7 hours. The solvent was removed under reduced pressure and the residue shaken with ethyl acetate/water. The organic extract was washed with water, dried over magnesium sulphate, filtered and the solvent removed from the filtrate under reduced pressure. After purification using column chromatography (Woelm silica/CHCl3:Et2O, 94:6) Compound l in Table l was obtained as a yellow oil (0.87 g, 70percent). Patent; IMPERIAL CHEMICAL INDUSTRIES PLC; EP248554; (1987); (A2) English

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View in Reaxys 64%

50 : Recrystallization: ethyl ether Recrystallization: ethyl ether Yield: 64percent Melting point: 130° C. Patent; Adir et Compagnie; US5332735; (1994); (A1) English View in Reaxys

53%

(Operation and Results) (Operation and Results) A 200-ml three-necked flask was charged with ion-exchanged water, concentrated hydrochloric acid and PdCl2 and they were slowly dropped into an EtOH solution of PPh3 under stirring by employing a cannula (while it was heated to 60° C. in an oil bath). Their dropping was followed by three hours of stirring at 60° C. Insoluble matter (intended product) was collected by filtration and was cleansed with 100 ml of boiled water, then 100 ml of hot EtOH and then 100 ml of hot Et2O (a gross amount of 2.09 g was obtained at a gross yield of 53percent). Patent; National University Corporation Gunma University; US2008/265750; (2008); (A1) English View in Reaxys

51%

3.a : α-Ac-Ile-Thr-Gly-Lys-pNA.HCl Molecular weight=616.13 3a) α-Boc-O-Bzl-Thr-Gly-ε-Lys-pNA Molecular weight=748.2 10 ml TFA is added to 5 mmol α-Boc-Gly-ε-Z-Lys-pNA (2a) dissolved in 20 ml methylenchloride. The mixture is stirred for 30 minutes at room temperature and the substance is precipitated with diethylether. The dry substance is dissolved in 25 ml DMF and neutralized in cold (-10° C.) with Et3 N. To the solution 5 mmol α-Boc-O-Bzl-Thr-OH, 5 mmol HOBT and 5.1 mmol DCCl are added. The mixture is stirred for 1 hour in cold and overnight at room temperature. The formed DCU is filtered off and the solution is evaporated in vacuo to an oil, which is dissolved in EtOAc and washed with 2percent NaHCO3, 2percent KHSO4 and H2 O. After drying with Na2 SO4 the EtOAc phase is evaporated and the substance is precipitated with diethylether as an oil which solidifies in vacuo. Yield: 51percent Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys

50%

1.1 : EXAMPLE 1 1) α-Ac-Ile-Glu-Gly-Lys-pNA.HCl Molecular weight=644.15 10 ml triflic acid is added to a cold (-10° C.) suspension of 1 mmol α-Ac-Ile-γ-O-Bzl-Glu-Gly-Z-Lys-pNA-(1f) in 10 ml methylenchloride. The mixture is stirred for 50 minutes at room temperature and precipitated with diethylether. The dried substance is ion exchanged on a Sephadex.(R). QAE-25 column, in chloride form with 50percent ETOH as eluent and is purified on a Merck Lobar.(R). prepacked column (Lichroprep..(R). RP-8-B) with 50percent MeOH as eluent (2 ml/minute). The purified product is lyophilized. Yield: 42percent TLC: Rf=0.2 (Pa6) HPLC: 98percent purity [α]D 25 =-63.1° (C=0.5percent) Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys

50%

16 : (B) Ethyl ether containing anhydrous hydrochloric acid was then added and the precipitate was filtered. The precipitate was then suspended in water and made alkaline by the addition of sodium carbonate and the aqueous phase was extracted with ether.

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The ethereal phase was dried, anhydrous hydrochloric acid was added and the precipitate of hydrochlorides formed was isolated. The end product was isolated after repeated recrystallisations from isopropanol; yield 50percent. Patent; C.E.R.P.H.A. a French Society organised under the laws of France; US4029808; (1977); (A1) English View in Reaxys 49%

5percent triethylamine: 95percent[ether], 49percent yield; IR (CDCl3)3692, 3607, 2940, 1695, 1602, 1470 cm-1; 1 H NMR (CDCl3)δ: 7.75 (m, 3H), 7.56 (s, br 1H), 7.42 (m, 2H), 7.30 (dd, 1H, J=8.5 and 1.8 Hz), 3.75 (ddd, 1H, J=6.3, 3.1 and 3.1 Hz), 3.60 (d, br, 1H, J=5.7 Hz), 3.37 (ddd, 1H, J=12.7, 5.4 and 5.4 Hz), 3.01 (d, br, 1H, J=5.9 Hz), 2.57 (ddd, 1H, J=13.0, 13.0 and 2.9 Hz), ca. 2.50-2.45 (s, br, 1H), 2.19 (q, 1H, J=7.2 Hz), 2.10 (q, 1H, J=7.2 Hz), 2.09 (m, 1H), 1.84-1.50 (m, 4H), 1.18 (d, 6H, J=7.0 Hz), 0.59 (t, 3H, J=7.2 Hz); 13 C NMR (CDCl3)δ: 214.9, 139.9, 133.4, 132.2, 127.9, 127.8, 127.5, 126.2, 126.0, 125.5, 56.3, 55.9, 53.6, 38.7, 36.8, 34.0, 29.2, 27.7, 24.0, 7.0; MS m/z 293 (M+, 43percent), 275 (11), 244 (9), 236 (49), 222 (9), 195 (6), 178 (19), 165 (23), 152 (27), 141 (15), 128 (16), 83 (100), 82 (80), 68 (97), 57 (29), 41 (22). Anal. Calcd for C20 H23 NO.0.7H2 O: C, 78.50; H, 8.04; N, 4.58. Found: C, 78.46; H. 7.69; N, 4.58. Patent; Wake Forest University; US5760055; (1998); (A1) English View in Reaxys

48.3%

Preparation of MPEG-Cl (Step 1, Chart A) Preparation of MPEG-Cl (Step 1, Chart A) MPEG-Cl was prepared by chlorination of MPEG 750 with thionyl chloride following the procedure of Bayer, et al. Bayer, E., Zheng, H., and Geckeler, K. 1982. Functionalization of soluble polymers 4. Synthesis of dichloro- and di(4-formylphenyloxyethyl) poly(oxyethylene). Poly. Bull. 8:585-592. In a typical reaction, 35 g of MPEG 750 (34.4 mmoles) was dried by azeotropic distillation from toluene in vacuo. Following addition of 95 mL (1.3 moles) of freshly distilled thionyl chloride the reaction was refluxed for 9 hours under a nitrogen atmosphere. Excess thionyl chloride was then removed by vacuum distillation. The yellow residue was dissolved in 50 mL of chloroform, vacuum filtered, and precipitated with 500 mL of diethyl ether at -20° C. The product was recrystallized twice from chloroform/diethyl ether (1:10, v:v) and dried under vacuum to yield 12.72 g. (48.3percent yield) of MPEG-Cl (MW 768.45). FTIR results indicate complete conversion to the monochloride: (neat) 663 cm-1 (C-Cl), no absorption for OH at 3473 cm-1. Patent; Baxter Biotech Technology Sarl; US5907035; (1999); (A1) English View in Reaxys

46%

2β-Propanoyl-30-(4-methylphenyl)-8-azabicyclo[3.2.1]octane (WF-49). 5percent triethylamine: 45percent ether: 50percent pentane! then 5percent triethylarine: 95percent[ether], 46percent yield; IR (CDCl3) 3687, 3605, 2925, 1699, 1602, 1377, 1096 cm-1; 1 H NMR (CDCl3)δ: 7.03 (d, 2H, J=6.3 Hz), 7.02 (d, 2H, J=6.1 Hz), 3.71 (m, 1H), 3.58 (dbr, 1H, J=5.3 Hz), 3.18 (dt, 1H, J=13.1 and 5.3 Hz), 2.88 (d br, 1H, J=5.3 Hz), 2.81 (s, br, 1H), 2.40 (td, 1H, J=13.1 and 2.8 Hz), 2.21-2.00 (m, 3H), 1.79-1.50 (m, 4H), 0.67 (t, 3H, J=7.2 Hz); 13 C NMR (CDCl3)δ: 215.3, 139.0, 136.1, 129.1, 127.4, 56.2, 55.8, 53.6, 38.8, 36.2, 33.8, 29.0, 27.5, 21.0, 7.0; MS m/z 257 (M+, 29percent), 239 (30), 237 (21), 210 (32), 208 (32), 200 (39), 159 (7), 148 (10), 142 (10), 128 (15), 118 (26), 117 (26), 115 (27), 105 (20), 91 (30), 83 (86), 82 (60), 69 (76), 68 (100), 57 (36), 54 (20), 41 (32). Anal. Calcd for C19 H27 NO.0.25H2 O: C, 78.71; H, 9.56; N, 4.83. Found:C, 78.73; H, 9.58; N, 4.72. Patent; Wake Forest University; US5760055; (1998); (A1) English View in Reaxys

41%

8.b : Preparation of (d) and (e) Step 8b Preparation of (d) and (e) A mixture of (c) (0.804 g, 3.17 mmol), 10percent Pd/C (0.08 g) and ethyl acetate (10 mL) was stirred under a hydrogen atmosphere for 3 hrs, then filtered to remove the catalyst and washed with ethyl acetate (2*5 mL). The resulting solution was divided into two portions of equal volume and to each was added WSCDI (0.457 g, 2.37 mmol), 1-hydroxybenzotriazole (0.321 g, 2.37 mmol), NMM (0.524 mL, 4.75 mmol) and DMF (10 mL). 2-Phenylaminobenzoxazole-6-acetic acid (0.467 g, 1.74 mmol) was added to one mixture and 4-methoxy-2-phenylaminobenzoxazole-6-acetic acid (0.519 g, 1.74 mmol) was added to the other. Both reactions were placed under a drying tube and stirred at room temperature overnight.

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The solvents were removed in vacuo, and each reaction was subjected to the following work-up: ethyl acetate (150 mL) was added and the mixture was washed sequentially with water (75 mL), saturated sodium bicarbonate solution (3*75 mL), water (75 mL) and brine (75 mL). The organic phase was dried (MgSO4), filtered, concentrated to dryness and purified by column chromatography (40 g Si) eluding with increasingly polar mixtures of methanol and DCM to give the title compound (d) as a brown solid (0.311 g, 41percent), and compound (e) as a purple solid which was dissolved in a small volume of DCM and precipitated by addition of diethyl ether, collected by filtration and dried (0.564 g, 71percent). Patent; AstraZeneca AB; US2003/181498; (2003); (A1) English View in Reaxys 40%

46 : Recrystallization: acetonitrile/ethyl ether Recrystallization: acetonitrile/ethyl ether Yield: 40percent Melting point: 128° C. Patent; Adir et Compagnie; US5332735; (1994); (A1) English View in Reaxys

40%

58 : Recrystallization: ethyl ether Recrystallization: ethyl ether Yield: 40percent Melting point: 92° C. Patent; Adir et Compagnie; US5332735; (1994); (A1) English View in Reaxys

38%

Compound 115: To a suspension of NaH (60percent in mineral oil, 7.1 mg, 0.18 mmol) in THF (2 mL) was added the oxindole 114b (40 mg, 0.12 mmol) under nitrogen. The mixture was heated at reflux temperature, and ethyl trifluoroacetate (21 μL, 0.18 mmol) was added. After 2 hours of reflux the mixture was cooled to room temperature and poured into 1M aq. HCl. The product was extracted into ethyl acetate (2*15 mL). The combined organic extracts were washed with brine and dried (MgSO4). The pure product 117 was obtained by precipitation from diethyl ether (20 mg, 38percent) as a grey solid. 1H NMR (DMSO) δ 7.98 (d, J=7.5 Hz, 1H), 7.93 (d, J=6.9 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H), 7.58 (m, 2H), 6.85 (m, 3H), 5.49 (s, 2H), 4.54 (br s, 2H), 4.35 (dt, J=5.7, 47 Hz, 2H), 1.66 (m, 4H); MS m/e 434 (MH+). Patent; Yu, Kuo-Long; Civiello, Rita L.; Combrink, Keith D.; Gulgeze, Hatice Belgin; Sin, Ny; Wang, Xiangdong; Meanwell, Nicholas; Venables, Brian Lee; Zhang, Yi; Pearce, Bradley C.; Yin, Zhiwei; Thuring, Jan Willem; US2002/99208; (2002); (A1) English View in Reaxys

36%

3.3 : α-Ac-Ile-Thr-Gly-Lys-pNA.HCl Molecular weight=616.13 3) Ac-Ile-Thr-Gly-Lys-pNA.HCl Molecular weight=616.13 10 ml triflic acid is added to a cold (-10° C.) suspension of 1 mmol α-Ac-Ile-O-Bzl-Thr-Gly-ε-Z-Lys-pNA (3c) in 10 ml methylenchloride. The mixture is stirred for 50 minutes at room temperature and precipitated with diethylether. The product is ion exchanged and purified in the same way as in example 1. Yield: 36percent TLC: Rf=0.21 (Pa6) HPLC: 97percent purity [α]D 25 =-53.2° (c=0.3percent) Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys

35%

2.2 : α-Ac-Ile-Ser-Gly-Lys-pNA.HCl Molecular weight=602.11 2) α-Ac-Ile-Ser-Gly-Lys-pNA.HCl Molecular weight=602.11 10 ml triflic acid is added to a cold (-10° C.) suspension of 1 mmol α-Ac-Ile-O-Bzl-Ser-Gly-ε-Z-Lys-pNA (2d) in 10 ml methylenchloride.

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The mixture is stirred for 50 minutes at room temperature and precipitated with diethylether. The product is ion exchanged and purified in the same way as in example 1. Yield: 35percent TLC: Rf=0.2 (Pa6) HPLC: 97percent purity. [α]D 25 =-50.1° (c=0.5percent) Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys 31%

4 : 4α-Ac-Ile-Glu-Glyc-Arg-pNA.HCl Molecular weight=673.18 10 ml triflic acid is added to a cold (-10° C.) suspension of 1 mmol α-Ac-Ile-γ-O-Bzl-Glu-Glyc-Arg-pNA.HCl (4d) in 10 ml methylenchloride. The mixture is stirred for 50 minutes at room temperature and precipitated with diethylether. The substance is ion exchanged and purified in the same way as in example 1. Yield: 31percent Patent; Chromonogenix AB; US5334703; (1994); (A1) English View in Reaxys

10%

a : a) A mixture of tributylphosphine (1.16 mL, 4.72 mmol), dimethyl disulfide (0.31 mL, 3.54 mmol) and ethyl (2SR, 1'SR, 2'RS,3'RS)-N-(tert-butoxycarbonyl)-2-[2'-(ethoxycarbonyl)-3'-(hydroxymethyl)cyclopropyl]glycinate (410 mg, 1.18 mmol) in dry tetrahydrofuran (8 mL), was stirred at 50° C. under argon for 20 h. Then, silicagel was added to the mixture and solvent was removed under reduced pressure. The resulting residue was purified by flash chromatography using hexane and diethylether 7:3 as eluent to afford 45 mg (10percent yield) of the title compound. 1H-NMR (200 MHz, CDCl ) δ: 5.30 (bd, 1H); 4.25-3.93 (m, 5H); 2.90 (m, 1H); 2.49 (m, 1H); 2.12 (s, 3H); 1.76 (m, 3 3H); 1.40 (s, 9H) and 1.29-1.12 (m, 6H) ppm. 13C-NMR (50 MHz, CDCl ) δ: 172.4; 171.0; 155.2; 80.1; 62.1; 61.7; 52.0; 32.4; 29.9; 28.2 (3C); 27.3; 25.7; 15.5 and 3 14.5 (2C) ppm. Patent; Eli Lilly and Company; US6498180; (2002); (B1) English View in Reaxys technische Darstellung Ullmann,F.; View in Reaxys weitere Untersuchungen und Betrachtungen ueber diesen 'kontinuierlichen' Aetherbildungsprozess Kremann; Monatshefte fuer Chemie; vol. 31; (1910); p. 276,671 View in Reaxys Villiers; Annales de Chimie (Cachan, France); vol. &lt;7&gt; 29; (1903); p. 561 View in Reaxys Oddo; Gazzetta Chimica Italiana; vol. 31 I; (1901); p. 299 View in Reaxys Prunier; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 124; (1897); p. 1239 View in Reaxys Nef; Justus Liebigs Annalen der Chemie; vol. 298; (1897); p. 322; Justus Liebigs Annalen der Chemie; vol. 318; (1901); p. 50 View in Reaxys Boullay; ; vol. 1; p. 97 View in Reaxys Wolf,J.F. et al.; Journal of the American Chemical Society; vol. 99; (1977); p. 5417 - 5429 View in Reaxys Kuhn,R.; Butula,I.; Justus Liebigs Annalen der Chemie; vol. 718; (1968); p. 50 - 77 View in Reaxys Romm,I.P. et al.; Tetrahedron; vol. 25; (1969); p. 2455 - 2468 View in Reaxys Frainnet,E.; Esclamadon,C.; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 254; (1962); p. 1814 - 1816

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View in Reaxys Bourhis,R.; Frainnet,E.; Journal of Organometallic Chemistry; vol. 86; (1975); p. 205 - 218 View in Reaxys Leonow; Korschunow; J. Gen. Chem. USSR (Engl. Transl.); vol. 32; (1962); p. 208,203; ; vol. 57; nb. 16372; (1962) View in Reaxys Kolker; Journal of the Chemical Society; (1964); p. 5929 View in Reaxys Nucci et al.; Tetrahedron Letters; (1977); p. 3099 View in Reaxys Wijnen; Journal of the American Chemical Society; vol. 82; (1960); p. 3034,3035 View in Reaxys Hellwinkel; Knabe; Chemische Berichte; vol. 104; (1971); p. 1761,1769, 1782 View in Reaxys Niklas; Chemische Berichte; vol. 96; (1963); p. 818,819 View in Reaxys Schmidt; Wilhelm; Zeitschrift fuer Anorganische und Allgemeine Chemie; vol. 330; (1964); p. 324,327 View in Reaxys Bagdasaryan et al.; Armyanskii Khimicheskii Zhurnal; vol. 30; (1977); p. 661,664, 666; ; vol. 88; nb. 89029d; (1978) View in Reaxys Tsurugi et al.; Journal of the American Chemical Society; vol. 91; (1969); p. 4587 View in Reaxys Denis; Kabel; AIChE Journal; vol. 16; (1970); p. 972,974, 975 View in Reaxys Nefedov; Mishin; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 28; (1979); p. 183,184,185; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; vol. 28; (1979); p. 196 View in Reaxys Dabrowski et al.; Journal of Catalysis; vol. 18; (1970); p. 297,309, 311 View in Reaxys Bansal; Freeman; Journal of the American Chemical Society; vol. 92; (1970); p. 4173 View in Reaxys Bristow; Tillett; Journal of the Chemical Society [Section] C: Organic; (1968); p. 684 View in Reaxys Bansal; Freeman; Journal of the American Chemical Society; vol. 90; (1968); p. 5632 View in Reaxys 4 : PEG-GFLF-DECD (Compound 11): PEG-GFLF-DECD (Compound 11): PEG-GFLG (tetrapeptide Gly-Phe-Leu-Gly grafted PEG polymer, compound 10, ~4.5 GFLG peptide in a PEG of 20,000 prepared from PEG-8PA and GFLG peptide) (2.0 g, ~0.4 mmole -COOH, dried by co-evaporation with 30 ml DMF) was dissolved in 30 ml anhydrous DMF and 0.17 ml of tributylamine (0.7 mmole, Fw=185.36, d=1.053) with protection of argon. To this was added 0.078 ml (0.6 mmole) isobutylchloroformate in 2 ml DMF after cooling to 0° C. The mixture was stirred at 0° C. for 1.5 hours, then slowly added to the solution of 2.0 g compound 9 in 20 ml DMF at room temperature, followed by addition of 0.087 ml of DIPEA (0.5 mmole). The mixture was stirred at room temperature overnight, concentrated to about 10 ml, precipitated with 90 ml of cold ethyl ether. The orange precipitate was collected by filtration and was further precipitated 3 times using ether from methanol. Patent; Salus Therapeutics, Inc.; US2003/144222; (2003); (A1) English View in Reaxys 1.ii : 1.2. ii) Peptide INF7 (sequence GLFEAIEGFIENGWEGMIDGWYGC) was synthesised according to the same procedure on 500 mg chlorotrityl resin (0.5 mmol/g), cleaved from the resin as described for YE5C and precipitated with diethyl ether. The raw product was dried in vacuo. Patent; Plank, Christian; Stemberger, Axel; Scherer, Franz; US2003/26840; (2003); (A1) English View in Reaxys Method F:

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Method F: Cleavage of the Boc Protecting Group 3 ml of 1.1N HCl/glacial acetic acid (Method Fl) or 3 ml of 1.1N HCl/dioxane (Method F2) or 3 ml of 50percent TFA in DCM (Method F3) are added to 1 mmol of Boc-protected amino acid pyrrolidide, thiazolidide or peptide. The cleavage at RT is monitored by means of TLC. After the reaction is complete (approximately 2 h), the compound is precipitated in the form of the hydrochloride using absolute diethyl ether and is isolated with suction and dried over P4O10 in vacuo. Using methanol/ether, the product is recrystallized or reprecipitated. Patent; Pospisilik, Andrew J.; Demuth, Hans-Ulrich; Glund, Konrad; Hoffmann, Matthias; McIntosh, Christopher H. S.; Pederson, Ray A.; US2003/176357; (2003); (A1) English View in Reaxys 14 : Preparation of Compound 17 Example 14 Preparation of Compound 17 To compound 16 (0.18 g, 0.48 mmol) was added compound 4 (0.14 g, 0.33 mmol), Pd(PPh3)4 (0.05 g, 0.49 mmol), and toluene (10 mL) in a sealed tube under an argon atmosphere. The solution was degassed with argon and heated at 135° C. in an oil bath for 3 h. The solution was cooled to room temperature, diluted with saturated NaHCO3, and extracted with CH2Cl2 (3*30 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give a light brown oil. The residue was purified by flash column chromatography using MeOH/CH2Cl2 (10percent) to afford 17 as a white solid. The sample was dissolved into hexane/CH2Cl2/MeOH and then precipitated with diethyl ether, filtered, and rinsed several times with ether to provide in 17 (30.3 mg): mp 95-100° C.; 1H NMR (300 MHz, CDCl3) δ 8.68 (d, 1H), 7.96 (d, 2H), 7.77-7.69 (m, 2H), 7.49-7.45 (m, 3H), 7.24-7.20 (m, 1H), 5.99 (s, 1H), 5.11 (s, 1H), 4.88-4.83 (m, 3H), 4.65-4.56 (m, 1H), 3.91-3.80 (m, 2H), 3.65-3.60 (m, 1H), 1.66-1.52 (m, 8H), 1.05-0.99 (t, 3H); IR (KBr) 3411, 2968, 1601, 1489 cm-1; CI MS m/z=432 [C24H29N7+H]+. Patent; Trova, Michael Peter; US2003/87906; (2003); (A1) English View in Reaxys 14 : Preparation of Compound 17 Example 14 Preparation of Compound 17 To compound 16 (0.18 g, 0.48 mmol) was added compound 4 (0.14 g, 0.33 mmol), Pd(PPh3)4 (0.05 g, 0.49 mmol), and toluene (10 mL) in a sealed tube under an argon atmosphere. The solution was degassed with argon and heated at 135° C. in an oil bath for 3 h. The solution was cooled to room temperature, diluted with saturated NaHCO3, and extracted with CH2Cl2 (3*30 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give a light brown oil. The residue was purified by flash column chromatography using MeOH/CH2Cl2 (10percent) to afford 17 as a white solid. The sample was dissolved into hexane/CH2Cl2/MeOH and then precipitated with diethyl ether, filtered, and rinsed several times with ether to provide in 17 (30.3 mg): mp 95-100° C.; 1H NMR (300 MHz, CDCl3) δ8.68 (d, 1H), 7.96 (d, 2H), 7.77-7.69 (m, 2H), 7.49-7.45 (m, 3H), 7.24-7.20 (m, 1H), 5.99 (s, 1H), 5.11 (s, 1H), 4.88-4.83 (m, 3H), 4.65-4.56 (m, 1H), 3.91-3.80 (m, 2H), 3.65-3.60 (m, 1H), 1.66-1.52 (m, 8H), 1.05-0.99 (t, 3H); IR (KBr) 3411, 2968, 1601, 1489 cm-1; CI MS m/z=432 [C24H29N7+H]+. Patent; Trova, Michael Peter; US2003/92909; (2003); (A1) English View in Reaxys C : Step C Step C The product from step B (1 eq.) is dissolved in MeCN (app. 20 ml/g), and conc. HCl is added (10 eq.). The reaction is left with stirring overnight, and evaporated in vacuo. The product is dissolved in EtOAc and water (1+1, app. 50 ml/g), separated, and the aqueous phase washed with EtOAc (2*25 ml/g). The aqueous phase is added an equal amount of 2N K2CO3, and extracted with EtOAc (3*25 ml/g). The combined EtOAc phase is washed with brine, dried (MgSO4), and about half the solvent is removed by evaporation in vacuo. Conc. HCl is added (1.1 eq.), and the solvent is evaporated in vacuo. The product is dissolved in hot EtOH, precipitated with Et2O, collected by filtration, and dried in vacuo.

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Patent; Kanstrup, Anders Bendtz; Sams, Christian Klarner; Lundbeck, Jane Marie; Christiansen, Lise Brown; Kristiansen, Marit; US2003/105077; (2003); (A1) English View in Reaxys F : Method F. Method F. Cleavage of the Boc Protecting Group 3 ml of 1.1 N HCl/glacial acetic acid (Method F1) or 3 ml of 1.1 N HCl/dioxane (Method F2) or 3 ml of 50percent TFA in DCM (Method F3) are added to 1 mmol of Boc-protected amino acid pyrrolidide, thiazolidide or peptide. The cleavage at RT is monitored by means of TLC. After the reaction is complete (approximately 2 h), the compound is precipitated out in the form of the hydrochloride using absolute diethyl ether and is isolated with suction and dried over P4O10 in vacuo. Using methanol/ether, the product is recrystallized or reprecipitated. Patent; Demuth, Hans-Ulrich; Hoffmann, Torsten; Glund, Konrad; Heiser, Ulrich; Hoersten, Stephan von; US2003/119750; (2003); (A1) English View in Reaxys H : Step 5-Preparation of (7R)-7-[2-(2-Amino-5-chlorothiazol-4-yl)-2-oxoacetamido]-3-(1-pyridinio)methyl-3cephem-4-carboxylate Bis-Trifluoroacetate The intermediate from Step 4 (0.11 g, 0.18 mmol) was dissolved in 5 mL of methanol and concentrated aqueous hydrochloric acid (0.5 mL) was added. The resulting solution was stirred at room temperature for 1.5 hours. The methanol was removed under vacuum and acetonitrile (10 mL) was added. The solution was then concentrated in vacuum and to the residue as added DCM (2 mL) and TFA (2 mL) and the resulting mixture was stirred at room temperature for 1.5 hours. Diethyl ether (50 mL) was then added and the title intermediate was isolated by centrifugation. This intermediate was used without further purification. MS m/z=479.9 (M)+. Patent; Fatheree, Paul R.; Linsell, Martin S.; Long, Daniel D.; Marquess, Daniel; Moran, Edmund J.; Nodwell, Matthew B.; Turner, S. Derek; Aggen, James; US2003/130173; (2003); (A1) English View in Reaxys 31 : EXAMPLE 31 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 1.1 : 9.1. 9.1. Trityl Deprotection for Single Compounds with Triethylsilane A solution of 0.58 mmol tritylsulfanyl in 5.8 ml TFA is treated at 0° C. with 0.92 ml (5.78 mmol) triethylsilane and after 10-30 min at RT evaporated and purified by flash chromatography on silicagel or precipitated from Et2O or Et2O/ pentane to give the thiol-compound. Patent; Aebi, Johannes; Blum, Denise; Bur, Daniel; Chucholowski, Alexander; Dehmlow, Henrietta; Kitas, Eric Argirios; Loeffler, Bernd Michael; Obst, Ulrike; Wallbaum, Sabine; US2002/49243; (2002); (A1) English View in Reaxys 100 : EXAMPLE 100 The butyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys

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101 : EXAMPLE 101 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 102 : EXAMPLE 102 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 μL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 103 : EXAMPLE 103 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 104 : EXAMPLE 104 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 105 : EXAMPLE 105 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 106 : EXAMPLE 106 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 107 : EXAMPLE 107 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted.

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Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 108 : EXAMPLE 108 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 109 : EXAMPLE 109 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 15 : Example 15 Example 15 The pentyl bromide intermediate (1.64 mmol, obtained from Example 13, Step 1) and N,N,N',N'-tetramethyl-1,6-hexanediamine (0.10 0 g, 0.580 mmol) in 5 mL of acetonitrile are placed in a 4 oz. Fischer Porter bottle. The reaction vessel is purged with nitrogen, sealed, equipped with magnetic stirrer and heated to 50° C. After 15 hours, the reaction mixture is cooled to ambient temperature and concentrated in vacuo to give a foamy solid. The solid is dissolved in acetonitrile and precipitated with ethyl ether to give the desired dibromide salt. Patent; Tremont, Samuel J.; Koeller, Kevin J.; Neumann, William L.; US2002/183307; (2002); (A1) English View in Reaxys 32 : EXAMPLE 32 The Phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 33 : EXAMPLE 33 The Butyl urea-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 34 : EXAMPLE 34 EXAMPLE 34 Fmoc-Linker-BHA resin (360 mg, 0.2 mmol) from Example 29 were subjected to solid phase synthesis using Protocol 1 above. All couplings were performed using HBTU in DMF as the coupling agent and DIPEA (3 equiv.) as base. Four coupling cycles were performed of one cycle each with), Fmoc-Trp (260 mg, 0.6 mmol) and HBTU (226 mg, 0.6 mmol), Fmoc-Arg (Cmc) (400 mg, 0.6 mmol) and HBTU (226 mg, 0.6 mmol), Fmoc-(D)Phe (240 mg, 0.6 mmol) and HBTU (226 mg, 0.6 mmol), Fmoc-Apc (275 mg 0.6 mmol) and HBTU (226 mg, 0.6 mmol).

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The peptide resin was carried through steps 1-5 of protocol 1, washed with CH2Cl2 (three times) and treated with 1 mL valeric anhydride in 6percent DIPEA/CH2Cl2 30 minutes. The resin was filtered and washed successively with 20 ml each of CH2Cl2 (two times), isopropanol, and CH2Cl2 (three times). The resin was dried under vacuum to yield 600 mg of pentyl-tetrapeptide resin. The Pentyl-tetra peptide resin was treated with, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 35 : EXAMPLE 35 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 36 : EXAMPLE 36 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 38 : EXAMPLE 38 The Butyl carbamoyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 39 : EXAMPLE 39 The benzoyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 40 : EXAMPLE 40 The 3-carboxypropanoyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 41 : EXAMPLE 41

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The phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 42 : EXAMPLE 42 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 43 : EXAMPLE 43 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 44 : EXAMPLE 44 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 45 : EXAMPLE 45 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 46 : EXAMPLE 46 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 47 : EXAMPLE 47 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 L trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted.

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Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 48 : EXAMPLE 48 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 L trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 49 : EXAMPLE 49 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 54 : EXAMPLE 54 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 μL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 55 : EXAMPLE 55 The Bu-carbamoyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 56 : EXAMPLE 56 The phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 57 : EXAMPLE 57 The Butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 58 : EXAMPLE 58

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The Butyl carbamoyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 59 : EXAMPLE 59 The phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 60 : EXAMPLE 60 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 mm. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 61 : EXAMPLE 61 EXAMPLE 61 A 1 oz. Fisher-porter bottle was charged with 0.14 g (0.34 mmoles) of 70112, 0.97 gms (6.8 mmoles) of methyl iodide, and 7 ml of anhydrous acetonitrile. Heat to 50° C. for 4 days. The quat. Salt Compound No. 192 was isolated by concentrating to 1 cc acetonitrile and then precipitating with diethyl ether. Patent; G.D. Searle and Co.; US2002/13476; (2002); (A1) English View in Reaxys 61 : EXAMPLE 61 The butyl-carbamoyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 62 : EXAMPLE 62 The phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 63 : EXAMPLE 63 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min.

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The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 64 : EXAMPLE 64 The butyl-carbamoyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 65 : EXAMPLE 65 The phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 66 : EXAMPLE 66 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 67 : EXAMPLE 67 The phenylacetyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 68 : EXAMPLE 68 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 69 : EXAMPLE 69 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English

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View in Reaxys 70 : EXAMPLE 70 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 mm. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 71 : EXAMPLE 71 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 72 : EXAMPLE 72 The butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 73 : EXAMPLE 73 The allyl protecting group was removed using PdCl2/Triphenylphosphine/tributyltin hydride under Argon in DMF. The guanidinylation was achieved using Boc-Guanidine. HCl (100 mg, 0.6 mmol) and HBTU (226 mg, 0.6 mmol). The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 74 : EXAMPLE 74 The Butyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 75 : EXAMPLE 75 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 76 : EXAMPLE 76

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The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 μL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 77 : EXAMPLE 77 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 78 : EXAMPLE 78 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 79 : EXAMPLE 79 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA, and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 80 : EXAMPLE 80 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 mm. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 82 : EXAMPLE 82 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 83 : EXAMPLE 83 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted.

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Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 84 : EXAMPLE 84 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 85 : EXAMPLE 85 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 86 : EXAMPLE 86 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 87 : EXAMPLE 87 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 88 : EXAMPLE 88 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 μL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 182 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 89 : EXAMPLE 89 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 90 : EXAMPLE 90

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The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 91 : EXAMPLE 91 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 92 : EXAMPLE 92 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 93 : EXAMPLE 93 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 94 : EXAMPLE 94 The butyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 95 : EXAMPLE 95 The butyl-carbamoyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 96 : EXAMPLE 96 The phenylacetyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted.

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Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 97 : EXAMPLE 97 The Pentyl-Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 98 : EXAMPLE 98 The 3-carboxylpropanoyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys 99 : EXAMPLE 99 The phenylacetyl Pentapeptide resin was treated with 40 μL ethanedithiol, 40 μL dimethylsulfide, 120 μL anisole, and 4 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA and the filtrates precipitated in chilled ethyl ether. The precipitates were centrifuged and the ether layer decanted. Patent; Chen, Li; Cheung, Adrian W.; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Yagaloff, Keith A.; US2001/56179; (2001); (A1) English View in Reaxys Trityl Deprotection Following Method 9.2.: A suspension of 865 mg (1.3 mmol) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid (1H-tetrazol-5-ylmethyl)-amide, 0.19 ml (1.4 mmol) 4-methoxybenzyl chloride, 0.19 ml (1.4 mmol) triethylamine and a spatula of sodium iodide in 10 ml acetone was heated at 75° C. for 15h. The reaction was partitioned between aqueous 10percent KHSO4/Et2O (3*). The organic phases were dried over Na2SO4 and precipitated from Et2O to give 1:1 mixture of (2S,4R)-1-(naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid 1-(4-methoxy-benzyl)-1H- and [2-(4-methoxy-benzyl)-2Htetrazol-5-ylmethyl]-amide, MS: 781 (MH+). Patent; Aebi, Johannes; Blum, Denise; Bur, Daniel; Chucholowski, Alexander; Dehmlow, Henrietta; Kitas, Eric Argirios; Loeffler, Bernd Michael; Obst, Ulrike; Wallbaum, Sabine; US2002/49243; (2002); (A1) English View in Reaxys [4R-[4a,5a(4R*,5R*)]]-N,N'-bis[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1benzothiepin-5-yl]phenoxy]pentyll-N,N,N'N'-tetramethyl-1,6-hexanediaminium dichloride [4R-[4a,5a(4R*,5R*)]]-N,N'-bis[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]pentyll-N,N,N'N'-tetramethyl-1,6-hexanediaminium dichloride The pentyl bromide intermediate (1.002 g, 1.64 mmol, obtained from Example 1418, Step 1) and N,N,N',N'-tetramethyl-1,6-hexanediamine (0.100 g, 0.580 mmol) in 5 mL of acetonitrile were placed in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer and heated to 50° C. After 15 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give an offwhite foamy solid (1.141 g). The solid was dissolved in acetonitrile and precipitated with ethyl ether. After cooling to 0° C., the solvent was decanted to yield a sticky off-white solid. This trituration method was repeated, and the resulting sticky solid was concentrated in vacuo to give the desired dibromide salt as an off-white foamy solid (0.843 g, quantitative): 1NMR (CDCl3) δ 0.85 (m, 12H), 1.01-1.70 (m, 30H), 1.76-2.08 (m, 12H), 2.18 (t, J=12.3 Hz, 2H), 2.79 (s, 12H), 3.03 (ABq, 4H), 3.35 (s, 12H), 3.52 (br s, 6H), 3.72 (br s, 4H), 3.97 (br s, 4H), 4.08 (br s, 2H), 5.42 (s, 2H), 6.00 (s, 2H), 6.51 (d, J=9.0 Hz, 2H), 6.86 (d, J=7.8 Hz, 4H), 7.38 (d, J=7.8 Hz, 4H), 7.83 (d, J=8.7 Hz, 2H).

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Patent; G.D. Searle and Co.; US2002/13476; (2002); (A1) English View in Reaxys 14 : Preparation of Compound 17 Example 14 Preparation of Compound 17 To compound 16 (0.18 g, 0.48 mmol) was added compound 4 (0.14 g, 0.33 mmol), Pd(PPh3)4 (0.05 g, 0.49 mmol), and toluene (10 mL) in a sealed tube under an argon atmosphere. The solution was degassed with argon and heated at 135° C. in an oil bath for 3 h. The solution was cooled to room temperature, diluted with saturated NaHCO3, and extracted with CH2Cl2 (3*30 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give a light brown oil. The residue was purified by flash column chromatography using MeOH/CH2Cl2 (10percent) to afford 17 as a white solid. The sample was dissolved into hexane/CH2Cl2/MeOH and then precipitated with diethyl ether, filtered, and rinsed several times with ether to provide in 17 (30.3 mg): mp 95-100° C.; 1H NMR (300 MHz, CDCl3) δ 8.68 (d, 1H), 7.96 (d, 2H), 7.77-7.69 (m, 2H), 7.49-7.45 (m, 3H), 7.24-7.20 (m, 1H), 5.99 (s, 1H), 5.11 (s, 1H), 4.88-4.83 (m, 3H), 4.65-4.56 (m, 1H), 3.91-3.80 (m, 2H), 3.65-3.60 (m, 1H), 1.66-1.52 (m, 8H), 1.05-0.99 (t, 3H); IR (KBr) 3411, 2968, 1601, 1489 cm; CI MS m/z=432 [C24H29N7+H]+. Patent; Trova, Michael Peter; US2002/91263; (2002); (A1) English View in Reaxys 17 : Synthesis of Naproxen-Succinimide After stirring overnight a precipitate formed. More precipitate was formed by the addition of 30-40 ml of H2O (containing 10 mg/ml Na2CO3), isolated by filtration and washed with 50 ml of Et2O. The fine white powder was dried (0.095 g, 53percent): 1H NMR (500 MHz, DMSO) 8.1 (m, 1H, lysine; amide), 7.8-7.0 (m, 6H, aromatic), 4.4 -4.1 (m, 2H, α methine), 3.3 (s, 3H, OCH3), 2.8 (m, 2H, ε), 1.7-1.0 (m, 9H,β, γ, δ CH3). Patent; Piccariello, Thomas; Olon, Lawrence P.; Kirk, Randal J.; US2002/99013; (2002); (A1) English View in Reaxys 1 : 3'-Deoxyadenylyl-(2'-5')-3'-deoxyadenylyl-(2'-5')-3'-deoxy-2'-O-[6-(tetradecanoylamino)-hexanoyl]adenosine (24). EXAMPLE 1 3'-Deoxyadenylyl-(2'-5')-3'-deoxyadenylyl-(2'-5')-3'-deoxy-2'-O-[6-(tetradecanoylamino)-hexanoyl]adenosine (24). A mixture of 22 (80 mg, 34 μmol) in CH2Cl2/MeOH 4:1 (4 ml) containing 2percent TsOH. H2O was stirred at r.t. for 20 min. Then the mixture was diluted with CHCl3 (30 ml) and washed with sat. NaHCO3 soln. (2*10 ml), the aq. phase reextracted with CHCl3, and the combined org. layer dried (MgSO4) and evaporated. The crude product was diluted with a small amount of CHCl3 and precipitated from Et2O (15 ml), centrifugated, and dried. Patent; Temple University-of the Commonwealth System of Higher Education; US6362171; (2002); (B1) English View in Reaxys 1 : N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1naphthamide The title compound could also be converted, in similar maimer, to the citrate hydrate (1.0:1.0:1.0). Alternately, the above titled compound was prepared by reacting the amine with 3-cyano-1-naphthoyl chloride. The required acid chloride was prepared as follows: a stirred mixture containing 3-cyano-1-naphthoic acid (0.18 g, 0.93 mmol) and dry DCM (7.5 mL) was treated with oxalyl chloride (0.14 g, 1.15 mmol) and dry DMF (10 μL) at ambient temperature. After 4 h, the solvent was evaporated in vacuo. The off-white solid residue was dissolved in dry DCM and used without further purification. Using standard acylation conditions 3-cyano-1-naphthoyl chloride was reacted with N-[(S)-2-(3,4-dichlorophenyl)-4[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methylamine. The product was converted to the citrate salt and isolated by filtration from Et2O to afford the citrate salt (740 mg) as a white solid. MS: m/z 632 (M+H). Patent; Astra Zeneca AB; US6365602; (2002); (B1) English

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View in Reaxys 4.B : Step B According to the method of Shrenik et al (J. Med. Chem., 35, 3745-3754 (1992)), R-α-n-propyl-(4-bromo)phenylmethyl isocyanate, prepared as in example 3, step B (1.32 g, 5.19 mmol) and 4-(pyridyl-3-oxy)-3,3-diethyl-2-azetidinone (0.573 mg, 2.60 mmol) gave, following purification by flash column chromatography (gradient from diethyl ether/petrol, 1:1 to diethyl etherlpetrol, 7:1 to diethyl etherlpetrol, 9:1), the title compound (0.35 g, 28percent) as an oil. Patent; Amersham International PLC; US6375926; (2002); (B1) English View in Reaxys 4 : Preparation of Compound 4. EXAMPLE 4 Preparation of Compound 4. To a solution of Compound 3 (10 mmol) in N,N-dimethylformamide (DMF, 50 mL) is slowly added 4-fluorosulfonylbenzoyl chloride (11 mmol) at room temperature. The reaction mixture is stirred at room temperature until Compound 3 is completely consumed. The solution is then carefully poured onto crushed ice/water, and filtered to collect the resulting solid. The crude solid is redissolved in DMF, and precipitated with ethyl ether. The solubilization/precipitation process is repeated twice to give the desired product (3.8 g). Patent; Haugland, Richard P.; Steinberg, Thomas H.; Patton, Wayne F.; Diwu, Zhenjun; US2002/137068; (2002); (A1) English View in Reaxys 5.1 : 5.1. 5.1. Synthesis of meso-tetrakis[4-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)phenyl]porphyrinato diaquamanganese (III) pentaiodide, Structural Formula ix 10.6 mL of methyl iodide was added to a solution of Structural Formula iii (0.50 g, 0.34 mmol) in 50 mL DMF at room temperature. The mixture was stirred 3 h. After concentration under vacuum, the crude product was dissolved in a minimum quantity of methanol and precipitated by adding diethylether. Patent; Eukarion, Inc.; US6403788; (2002); (B1) English View in Reaxys 54 : Preparation of Ac-Nle-cyclo(Cys-Cys)-Cys-Apc-(D)Phe-Arg-Trp-Cys-NH2 The Ac-heptapeptide resin was treated with 100 μL ethanedithiol, 100 μL dimethylsulfide, 250 μL anisole, and 10 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. Patent; Chen, Li; Cheung, Adrian Wai-Hing; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Wang, Yao; Yagaloff, Keith Alan; US2002/143141; (2002); (A1) English View in Reaxys 6.1 : 6.1. 6.1. Synthesis of meso-tetrakis[3-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)-2,4,6-trimethylphenyl]porphyrinato diaqua-manganese (III) pentaiodide, Structural Formula x 8.0 mL of methyl iodide was added to a solution of Structural Formula vii (0.41 g, 0.26 mmol) in 40 mL DMF at room temperature. The mixture was stirred for 3 h. After concentration under vacuum, the crude product was dissolved in the minimum quantity of methanol and precipitated by adding diethylether. Patent; Eukarion, Inc.; US6403788; (2002); (B1) English View in Reaxys 7.1 : 7.1. 7.1. Synthesis of meso-tetrakis[3-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)-2,4,6-trimethylphenyl]porphyrinato diaqua-iron(III) pentaiodide, Structural Formula xi

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8.0 mL of methyl iodide was added to a solution of Structural Formula vii (0.26 g, 0.16 mmol) in 25 mL DMF at room temperature. The mixture was stirred 3 h. After concentration under vacuum, the crude product was dissolved in the minimum quantity of methanol and precipitated by adding diethylether. Patent; Eukarion, Inc.; US6403788; (2002); (B1) English View in Reaxys 70 : Preparation of Ac-Nle-cyclo(Cys-Cys)-Cys-(D,L)Atc-(D)Phe-Arg-Trp-Cys-NH2 The Acetyl-hepta peptide resin was treated with 100 μL ethanedithiol, 100 μL dimethylsulfide, 250 μL anisole, and 10 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with ~2 ml TFA, and the filtrates precipitated in chilled ethyl ether. Patent; Chen, Li; Cheung, Adrian Wai-Hing; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Wang, Yao; Yagaloff, Keith Alan; US2002/143141; (2002); (A1) English View in Reaxys 71 : Preparation of Penta-cyclo(Cys-Cys)-Cys-5-Br(D,L)Atc-(D)Phe-Arg-Trp-Cys-NH2 The pentyl-hexapeptide resin was treated with 100 μL ethanedithiol, 100 μL dimethylsulfide, 250 μL anisole, and 10 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA, and the filtrates precipitated in chilled ethyl ether. Patent; Chen, Li; Cheung, Adrian Wai-Hing; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Wang, Yao; Yagaloff, Keith Alan; US2002/143141; (2002); (A1) English View in Reaxys 82 : Preparation of Penta-cyclo(Asp-Lys)-Asp-Abc-(D) Phe-Arg-Trp-Lys-NH2 The Pentyl-hexapeptide resin was treated with 100 μL ethanedithiol, 100 ZL dimethylsulfide, 250 μL anisole, and 10 mL trifluoroacetic acid at room temperature for 180 min. The resin was filtered off, washed with 2 ml TFA and the filtrates precipitated in chilled ethyl ether. Patent; Chen, Li; Cheung, Adrian Wai-Hing; Chu, Xin-Jie; Danho, Waleed; Swistok, Joseph; Wang, Yao; Yagaloff, Keith Alan; US2002/143141; (2002); (A1) English View in Reaxys 8 mg (70%)

167, R=H: A solution of the vinyl ether 190 (12 mg, 0. 029 mmol) in 1:1 1M HCl-THF (2 mL) was stirred at room temperature for 1 hour. The solvents were removed and the residue precipitated from diethyl ether to give 8 mg (70percent) of 191 as an offwhite solid. 1H NMR (DMSO) δ 8.65 (s, 1H), 8.07 (d, J=7.7 Hz, 1H), 7.74 (t, J=7.9 Hz, 1H), 7.68 (d, J=8.6 Hz, 1H), 7.60 (m, 2H), 7.40 (m, 2H), 7.25 (t, J=7.3 Hz, 1H), 6.02 (s, 2H), 5.71 (s, 1H), 4.54 (m, 2H), 2.61 (s, 3H), 1.89 (m, 4H); MS m/e 392 (MH+); Patent; Yu, Kuo-Long; Civiello, Rita L.; Combrink, Keith D.; Gulgeze, Hatice Belgin; Sin, Ny; Wang, Xiangdong; Meanwell, Nicholas; Venables, Brian Lee; Zhang, Yi; Pearce, Bradley C.; Yin, Zhiwei; Thuring, Jan Willem; US2002/99208; (2002); (A1) English View in Reaxys 5-Phenyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one Trituation of the crude product with diethyl ether yielded 5-phenyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one as a yellow solid (108 mg, 51.4percent). 1H NMR (d -DMSO): δ11.04 (s, 1H), 8.32 (s, 1H), 7.83 (s, 1H), 7.60 (d, 2H, J=7.4 Hz), 7.44 (t, 2H, J 7.4 Hz), 7.32 (t, 6 1H, J=7.4 Hz), 3.58 (s, 2H). MS (-ve APCI): 210 (48, M+), 209 (100, M-H). Patent; SmithKline Beecham Corporation; US6369086; (2002); (B1) English View in Reaxys 5-Phenyl-7-azaoxindole Trituation of the crude product with diethyl ether yielded 5-phenyl-7-azaoxindole as a yellow solid (108 mg, 51.4percent). 1H NMR (DMSO-d ): δ11.04 (s, 1H), 8.32 (s, 1H), 7.83 (s, 1H), 7.60 (d, 2H, J=7.4 Hz), 7.44 (t, 2H, J=7.4 Hz), 7.32 (t, 6 1H, J=7.4 Hz), 3.58 (s, 2H). MS (-ve APCI): 210 (48, M+), 209 (100, M-H).

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Patent; SmithKline Beecham Corporation; US6369086; (2002); (B1) English View in Reaxys Preparation of Example 1435 Preparation of 1,4-Diazabicyclo(2.2.2)octane (0.0785 g, 0.700 mmol) and acetonitrile (1.0 mL) were combined in a 10 mL roundbottom flask. The reaction flask was purged with N2, equipped with magnetic stirrer, and heated to 37° C. A solution of the product of Example 1434 (0.250 g, 0.432 mmol) in acetonitrile (2.50 mL) was added. After 2.5 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0200 g, 0.178 mmol) was added. After 64 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0490 g, 0.437 mmol) was added. After 24 hrs, the reaction mixture was cooled to R.T. and concentrated in vacuo. The crude product was dissolved in acetonitrile (2.0 mL) and precipitated with ethyl ether (10.0 mL). The precipitate was filtered to yield a white solid. This trituration method was repeated, followed by concentrated in vacuo to give a white solid (0.185 g, 62percent). mp 218.0-225.0° C.; 1H NMR (CD3OD) δ0.90 (m, 6H), 1.05-1.55 (m, 10H), 1.16 (t, J=6.6 Hz, 2H), 1.78 (m, 1H), 2.12 (m, 3H), 2.76 (s, 6H), 3.10 (m, 2H), 3.17 (t, J=7.2 Hz, 6H), 3.30-3.50 (m, 8H), 4.10 (s, 1H), 4.21 (t, J=5.4 Hz, 2H), 5.31 (s, 1H), 6.10 (s, 1H), 6.55 (d, J=7.2 Hz, 1H), 7.25 (d, J=6.9 Hz, 1H), 7.33-7.42 (m, 2H), 7.56 (s, 1H), 7.76 (d, J=9.0 Hz, 1H). HRMS. Calc'd for C36H55N4O5SCl: 655.3893. Found: 655.3880. Patent; G.D. Searle and Co.; US6387924; (2002); (B2) English View in Reaxys [4R-[4a,5a(4R*,5R*)]]-N,N'-bis[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1benzothiepin-5-yl]phenoxy]pentyl]-N,N,N'N'-tetramethyl-1,6-hexanediaminium dichloride [4R-[4a,5a(4R*,5R*)]]-N,N'-bis[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]pentyl]-N,N,N'N'-tetramethyl-1,6-hexanediaminium dichloride The pentyl bromide intermediate (1.002 g, 1.64 mmol, obtained from Example 1418, Step 1) and N,N,N',N'-tetramethyl-1,6-hexanediamine (0.100 g, 0.580 mmol) in 5 mL of acetonitrile were placed in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer and heated to 50° C. After 15 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give an offwhite foamy solid (1.141 g). The solid was dissolved in acetonitrile and precipitated with ethyl ether. After cooling to 0° C., the solvent was decanted to yield a sticky off-white solid. This trituration method was repeated, and the resulting sticky solid was concentrated in vacuo to give the desired dibromide salt as an off-white foamy solid (0.843 g, quantitative): 1H NMR (CDCl3) δ0.85 (m, 12H), 1.01-1.70 (m, 30H), 1.76-2.08 (m, 12H), 2.18 (t, J=12.3 Hz, 2H), 2.79 (s, 12H), 3.03 (ABq, 4H), 3.35 (s, 12H), 3.52 (br s, 6H), 3.72 (br s, 4H), 3.97 (br s, 4H), 4.08 (br s, 2H), 5.42 (s, 2H), 6.00 (s, 2H), 6.51 (d, J=9.0 Hz, 2H), 6.86 (d, J=7.8 Hz, 4H), 7.38 (d, J=7.8 Hz, 4H), 7.83 (d, J=8.7 Hz, 2H). Patent; G.D. Searle and Co.; US6387924; (2002); (B2) English View in Reaxys 3.c : b c) Preparation of H2N-PEG3400-CO2 -NH4 +: MsO -OCH2CO2CH3 (13 g) was dissolved in 70 ml of H2O and the pH was adjusted to 12. After stirring for 1.5 h while maintaining the pH at 12, 250 of NH4OH solution containing 5percent NH4Cl was added. The reaction mixture was then stirred for about 40 h NaCl was added to bring its concentration to about 8percent. The resulting solution was extracted with CH2Cl2 and dried over Na2SO4. The CH2Cl2 phase was evaporated to about 20 ml and precipitated with about 300 ml of cold ethyl ether. The precipitated product was collected by filtration and dried under vacuum at room temperature. The yield was 12.5 g. The purity was 97percent by 1H nmr and 95percent pure by GPC. Patent; Shearwater Corporation; US6448369; (2002); (B1) English View in Reaxys 1.B.i : 1B(i). 1B(i).

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2-(4-Fluorophenyl)-1-(4-methoxyphenyl)ethan-1-one A suspension of magnesium turnings (2.4 g, 100 mmol) in anhydrous diethyl ether (200 mL) was prepared. Patent; Abbott Laboratories; US6472416; (2002); (B1) English View in Reaxys 3.B : (A) (B) E/Z 1-[4-(2-Phenyl-4-oxazolyl)ethoxy)phenyl]-1-Methylsulfonyl-2-N,N-Dimethylamino Ethene. A stirred solution of 1.06 g (2.7 mM) of the intermediate prepared in part (A) above in 20 mL THF was treated with 1.0 mL (7.5 mM) of DMA and heated to reflux 2 h. The resulting brown solution was kept at room temperature for 8 to 16 hours, refluxed an additional 8 h and then evaporated. Trituration of the gummy residue with Et2O produced a soft white powder. Recrystallization from THF/i-PrOH afforded 1.14 g (95percent) of product as white flakes m.p. 143-154° C. Anal. Cal. For C23H24N2O5S (MW 440): C, 62.71; H, 5.49; N, 6.36. Found: C, 62.77; H, 5.59; N, 6.19. MS: m/e 440 Patent; Eli Lilly and Company; US6617342; (2003); (B1) English View in Reaxys 4.A : A. A. Preparation of [Fe(tachpyr)]Cl2 (1) A pale green solution of FeCl2.4H2O (0.0229 g, 1.15*104 mol) in methanol (2 mL) was degassed in a Schlenk flask by purging with N2 for 5 min. A similarly degassed yellow solution of tachpyr (0.0464 g, 1.15*104 mol) in methanol (2 mL) was added. The mixture attained a brown color while stirring for 30 min at 0° C. under N2. Layering with Et2O produced a brown precipitate that was isolated by filtration under N2, dried under reduced pressure, and stored under N2 in a Schlenk flask. 1H NMR (DMSO-d6, 360 MHz, 25° C.): d 7.80, 7.58, 7.26, 6.98 (t, d, t, d, 4H, C5H4N); 5.55 (t, 1H, NH); 4.43, 4.10 (ABX, 2H, py-CH2); 3.07 (s, 1H, cyclohexyl methine H); 2.09, 1.86 (AB,J=14.8 Hz, 2H, cyclohexyl methylene H's, diastereotopic). Air-sensitivity of the product interfered with further characterization. Patent; Wake Forest University Health Sciences; University of New Hampshile; National Institutes of Health; US6589966; (2003); (B1) English View in Reaxys G.10 : (R)-3-Hydroxy-4-methyl-3-(2-phenyl-ethyl)-pentanoic acid EXAMPLE G-10 (R) (R)-3-Hydroxy-4-methyl-3-(2-phenyl-ethyl)-pentanoic acid The mother liquor from the isolation of diastereomeric salt G-10 (S) was treated with 1N HCl and extracted with EtOAc. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to liberate the free β-hydroxy acid. HPLC analysis indicated the isolated material was 73percent (R):27percent (S). β-Hydroxy acid G-10 (1 equiv.) was dissolved in 600 mL EtOAc and treated with (R)-α-methylbenzylamine (0.74 equiv.). The resulting suspension was placed on a steam bath and heated to reflux. The solution was allowed to cool to room temperature slowly and then cooled to 0° C. in an ice bath. The resulting solids were filtered off and washed with cold EtOAc followed by Et2O to yield the title compound. Patent; Warner-Lambert Company; US6528510; (2003); (B1) English View in Reaxys G.3 : (R)-3-[2-(3,4-Difluoro-phenyl)-ethyl]-3-hydroxy-4-methyl-pentanoic acid EXAMPLE G-3 (R) (R)-3-[2-(3,4-Difluoro-phenyl)-ethyl]-3-hydroxy-4-methyl-pentanoic acid Compound G-3 (16.0 g, 58.8 mmol) from Table H was dissolved in 150 mL EtOAc and treated with (S)-α-methylbenzylamine (3.77 g, 31.14 mmol). The thick suspension that resulted was placed on a steam bath and heated to reflux. Additional EtOAc (240 mL) was added, followed by hot isopropanol (approximately 80 mL), until the solids dissolved.

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The solution was allowed to cool to room temperature slowly overnight. The mixture was then cooled to approximately 0° C. The resulting solids were filtered and washed with cold EtOAc followed by Et2O to yield the desired enantiomer. HPLC analysis of isolated solid (as the free acid): (AD chiralpak column, 1 mL/min., 97.5percent Hexanes:2.5percent IPA+0.1percent TFA) retention time: 23.80 min. (7.7percent) Patent; Warner-Lambert Company; US6528510; (2003); (B1) English View in Reaxys G.3 : (S)-3-[2-(3,4-Difluoro-phenyl)-ethyl]-3-hydroxy-4-methyl-pentanoic acid EXAMPLE G-3 (S) (S)-3-[2-(3,4-Difluoro-phenyl)-ethyl]-3-hydroxy-4-methyl-pentanoic acid The mother liquor from the isolation of diastereomaric salt G-3 (R) was treated with 1N HCl and extracted with EtOAc. The organic phased was washed with brine, dried (MgSO4), filtered and concentrated to liberate compound G-3. HPLC analysis indicated the isolated material was 78percent (S):22percent (R) based on comparison with previously isolated solid (diastereomaric salt G-3 (R)). β-Hydroxy acid G-3 (9.75 g, 35.8 mmol) was dissolved in 100 mL EtOAc and treated with (R)-α-methylbenzylamine (3.25 g, 26.86 mmol). The resulting thick suspension was placed on a steam bath and heated to reflux. Additional EtOAc (50 mL) was added, followed by hot IPA (100 mL), a little at a time until the solids dissolved. The solution was allowed to cool to room temperature overnight. The mixture was then cooled to 0° C. in an ice bath. The resulting solids were filtered and washed with cold EtOAc followed by Et2O. Patent; Warner-Lambert Company; US6528510; (2003); (B1) English View in Reaxys 3-(4-{[(trans-4-Cyclohexylcyclohexyl)-(4-trifluoromethoxybenzyl)amino]methyl}benzoylamino)propionic Acid The above ester was dissolved in THF, and excess 1M LiOH was added. After stirring at room temperature for 16 hours, the solution was acidified with 1N HCl to pH=4, and concentrated. The residue was dissolved in acetone (15 mL), filtered by suction, and the filtrate was concentrated. On addition of ethyl ether the title compound crystallized. Yield: 65 mg. 1H NMR (DMSO-d , D O, NaOD): δ0.80-1.82 (m, 20H), 2.13 (t, 2 H), 2.60 (t, 1H), 3.33 (t, 2H), 3.55 (s, 2H), 3.57 (s, 6 2 2H), 7.22 (d, 2H), 7.36 (d, 2H), 7.42 (d, 2H), 7.68 (d, 2H). MS (APCI, pos.): 561.2 (M+1). Patent; Noro Nordisk A/S; US6503949; (2003); (B1) English View in Reaxys 18 : Synthesis of nitrate Vc Example 18 Synthesis of nitrate Vc 3 g (8.88 mmol) of 1,4-dibromo-2,3-dinitrobutanediol and 2.81 (18 mmol) of Na2S2O3.5H2O were dissolved in a mixture of 100 mL of MeOH and 45 mL of H2O. The resulting solution was heated during 4 days at 40-45°. After this time the reaction mixture was partially evaporated to reduce the volume of solvents. The resulting mixture was extracted 4*50 mL of ethyl ether. The extracts were combined, washed (H2O), dried (MgSO4) and evaporated to minimum. Column chromatography afforded the title compound in 10percent yield, separated from Vb, the major product. Patent; Queen's University at Kingston; US6310052; (2001); (B1) English View in Reaxys 11 : EXAMPLE 11 EXAMPLE 11 In a 300 mL three-necked, round-bottomed flask were dissolved 5.2 g (34.4 mmole) of 4-amino-3-methylbenzoic acid in 75 ml of anhydrous methanol. Anhydrous hydrogen chloride was bubbled into the flask for 3 to 5 minutes and the resulting solution was refluxed for 2 hours.

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The solvent was removed using a rotary evaporator, the resulting residue was introduced into a mixture of 200 ml of water and 100 ml of methylene chloride and the mixture was then separated into two phases. The aqueous layer was made basic with 10percent aqueous sodium hydroxide and extracted with methylene chloride (3*100 ml). The combined organic layers were dried over anhydrous magnesium sulfate and the solvent removed using a rotary evaporator yielding 5.68 g methyl 4-amino-3-methylbenzoate. In a 300 mL three-necked, round-bottomed flask fitted with a magnetic stirrer, condenser equipped with nitrogen inlet, and thermometer were placed 5.68 (25 mmole) of methyl 4-amino-3-methylbenzoate and 35 mL of acetonitrile. The flask was immersed in a preheated oil bath (oil bath temperature 70° C.) and 5.15 g (37.8 mmole) of N-chlorosuccinimide was added all at once. The resulting mixture was refluxed for 2 hours then cooled to room temperature to stand overnight. The reaction mixture was concentrated by removing solvent using a rotary evaporator and the resulting residue was partitioned between a mixture of 100 ml of ethyl ether and 100 ml of water. Patent; Rohm and Haas Company; US5929098; (1999); (A1) English View in Reaxys 3 : EXAMPLE 3 After precipitation from Et2 O, the product was dissolved in 0.1percent aq CF3 COOH and was then lyophilised. This material was used directiy in the next step. Analytical RP-HPLC: tR =28.3 min, major peak (Vydac 218TP54, 0.46*25 cm, 1 mL/min, 20-35percent MeCN in 0.1percent CF3 COOH over 40 min, λ=215 nm). The Cys114,127 (SBut)-protected material was resuspended in H2 O. Concentrated aq ammonia solution (2 drops) was then added to bring the peptide material into solution. Pilot experiments using this procedure demonstrated that base treatment lead to very rapid removal of the t-butylsulphenyl protecting groups, as well as formation of the desired disulphide bond. The soluuon was then filtered and applied to an RP-HPLC column (Vydac 218TP1022, 2.2*25 cm). The column was developed at 5 mL.min with a gradient of 20 to 35percent MeCN in 0.1percent aq CF3 COOH over 2 hours. Appropriate peak fractions were pooled and lyophilised to afford pure title compound. Analytical RP-HPLC: tR =30.3 min, purity 92percent (Vydac 218TP54, 0.46*25 cm, 1 mL/min, 15-30percent MeCN in 0.1percent aq CF3 COOH over 40 min, λ=215 nm). ES-MS:[M]=5090.0, C211 H331 N65 O78 S2 =5090.44. Patent; Nycomed Imaging AS; US5948759; (1999); (A1) English View in Reaxys PREPARATORY EXAMPLES STR19 Combine 0.5 g (1.06 mmol) of the title compound of Preparative Example 4, 0.4 g (2.61 mmol) of the title compound of Preparative Example 1, 5 mL of dry DMF, and 0.5 mL (4.53 mmol) of 4-methylmorpholine, at 0° C., then add 0.6 g (3.12 mmol) of DEC and 0.4 g (2.96 mmol) of HOBT an stir the mixture overnight at 20° C. Concentrate in vacuo to a residue and extract the residue with CH2 Cl2 (2*50 mL). Wash the extracts with 25 mL of water, dry over MgSO4, then concentrate in vacuo to a residue and chromatograph (silica gel, 10percent MeOH/EtOAc+2percent NH4 OH (aqueous)) to give 0.6 g (93.7percent yield) of the title compound. Mass Spec.: MH+ =604.6 (FAB); partial 1 H NMR (CDCl3, 300 MHz): 8.48 (s, 1H); 8.16 (d, 2H); 7.61 (s, 1H); 7.29 (m, 1H); 7.18 (d, 2H); 7.04 (d, 1H); 3.71 (s, 2H). elemental analysis: calculated-C, 48.81; H, 4.10; N, 6.57 found-C, 49.10; H, 3.79; N, 6.74 STR58 Dissolve 5.9 g (9.78 mmol) of the title compound of Example 2 in 300 mL of 1:5 CH2 Cl2 /EtOAc at 0° C. Slowly add (dropwise) 3 mL of 4N HCl (aqueous) and stir the mixture at 0° C. for 5 min. Add 200 mL of Et2 O, collect the resulting solids by filtration and wash the solids with 50 mL of Et2 O. Dry the solids at 20° C. and 0.2 mm Hg to give 5.9 g (96percent yield) of the title compound. Mass Spec.: MH+ =604 (FAB). partial 1 H NMR (DMSO-d6, 300 MHz): d 8.66 (d, 2H); 8.51 (s, 1H); 7.95 (s, 1H); 7.67 (d, 2H); 7.47 (m, 1H); 7.15 (m, 1H); 3.99 (s, 2H). elemental analysis: calculated-C, 48.77; H, 3.62; N, 6.56 found-C, 48.34; H, 3.95; N, 6.84 STR59 Patent; Schering Corporation; US5925757; (1999); (A1) English View in Reaxys Preparation of MPEG-DECA (Step 3, Chart A) Preparation of MPEG-DECA (Step 3, Chart A)

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MPEG-DEA was converted to the bis-chlorinated product MPEG-diethylchloroamine (MPEG-DECA) with thionyl chloride following the procedure of Bayer, et al. In a typical reaction, 2 g of MPEG-DEA (2.39 mmoles) was dried by azeotropic distillation from toluene in vacuo. Following addition of 16 mL (219.4 mmoles) of freshly distilled thionyl chloride, the reaction was refluxed for 9 hours under a nitrogen atmosphere. Excess thionyl chloride was removed by vacuum distillation. The yellow residue was dissolved in 20 mL of chloroform, vacuum filtered, and precipitated with 200 mL of diethyl ether at -20° C. The product was recrystallized twice from chloroform/diethyl ether (1:10, v:v) and dried under vacuum to yield 1.44 g. (70.0percent) of MPEG-Cl (MW 874.05). FTIR results indicate complete conversion to the bis-chloride: (neat) 663 cm-1 (C-Cl), no absorption for OH at 3473 cm-1. Patent; Baxter Biotech Technology Sarl; US5907035; (1999); (A1) English View in Reaxys Preparation of MPEG-DETA (Step 5, Chart A) The upper polymer layer was removed, extracted with 10 mL of chloroform/ethanol (1:1.5, v:v), dried over anhydrous Na2 CO3 and precipitated with chilled diethyl ether at 4° C. Patent; Baxter Biotech Technology Sarl; US5907035; (1999); (A1) English View in Reaxys 45 : EXAMPLE 45 EXAMPLE 45 4-(3-Chloro-phenylamino)-3-(3-methoxy-benzylamino)-1H-pyrazolo[3,4-d]-pyrimidine (title compound I) and 5-(3chloro-phenyl)-1,5-dihydro-4-imino-3-(3-methoxy-benzylamino)-4H-pyrazolo[3,4-d]pyrmidine hydrochloride (title compound II) A mixture of 5.97 g (20 mmol) of 4-cyano-5-(dimethylamino-methyleneamino)-3-(3-methoxy-benzylamino)-pyrazole, 3.77 g (23 mmol) of 3-chloro-aniline hydrochloride and 100 ml of ethanol is heated under reflux for 36 hours. Cooling to approx. 10° C., filtering and washing the filter residue with ethanol yield title compound II; m.p. 251-253° C. (decomp.). The filtrate is concentrated by evaporation in vacuo, the oily residue is partitioned between ethyl acetate and water and the organic phase is washed with brine, dried over sodium sulfate and concentrated to a volume of approx. 25 ml using an RV, a crystalline precipitate being formed. Filtering and washing the filter residue with a small amount of ethyl acetate and diethyl ether yield title compound I (see Example 52); m.p. 194-195° C. The starting material is prepared as follows: Patent; Novartis AG; US5981533; (1999); (A1) English View in Reaxys 4.95 g (86%)

27 : Synthesis of 6.3 EXAMPLE 27 Synthesis of 6.3 To a cooled solution (0° C.) of 6.2 (5 g, 17.73 mmol) in dichloromethane (50 ml) is added dropwise N,N-diisopropylethylamine (DIPEA, 6.96 ml, 3.99 mmol) and chloromethyl methyl ether (MOMCI, 1.98 ml, 26.65 mmol). After stirring at room temperature for 3 hours, the mixture is brought to pH 1-2 and extracted with diethylether (3x). The combined organic fractions are washed with brine and saturated sodium bicarbonate, dried (Na2 SO4 anh.) and concentrated in vacuo. Purification by column chromatography (silica; hexane:acetone 95:5) yields 4.95 g (86percent) of the MOM diethylether of 6.2. Patent; Laboratoire Theramex S.A.; US6017907; (2000); (A1) English View in Reaxys 41 : 41f. 41g. 2-((1R,4S)-2-aza-3-(S)-bicyclo[2.2.1]heptyl)-furo[3,2-b]pyridine dihydrochloride A solution of 2-iodo-3-hydroxypyridine (0.4 g, 1.8 mmol), bis(triphenylphosphine)-palladium(II)chloride (0.06 g, 0.09 mmol), copper (I) iodide (0.05 g, 0.27 mmol), and NEt3 (0.25 mL, 1.8 mmol) in DMF (2 mL) was stirred for 1 hour. Then a solution of the product of example 41f (0.4 g, 1.8 mmol) in DMF (0.5 mL) was added. The mixture was heated at 60° C. for 16, quenched with saturated NaHCO3, and extracted with EtOAc (2*). The combined EtOAc extracts were washed with H2 O and brine, dried (MgSO4), and concentrated.

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The crude solid (0.64 g) was chromatographed (silica gel; hexane/EtOAc, 60:40) to give a yellow colored solid (0.27 g). This was dissolved in CH2 Cl2 and upon addition of HCl/Et2 O a solid precipitated which was collected and further purified by heating in MeOH with activated carbon for 15 minutes. Patent; Abbott Laboratories; US6001849; (1999); (A1) English View in Reaxys 61 : EXAMPLE 61 STR392 EXAMPLE 61 STR392 A 1 oz. Fisher-porter bottle was charged with 0.14 g (0.34 mmoles) of 70112, 0.97 gms (6.8 mmoles) of methyl iodide, and 7 ml of anhydrous acetonitrile. Heat to 50° C. for 4 days. The quat. Salt Compound No. 192 was isolated by concentrating to 1 cc acetonitrile and then precipitating with diethyl ether. Patent; G.D. Searle and Company; US5994391; (1999); (A1) English View in Reaxys 61 : Example 61 STR395 A 1 oz. Fisher-porter bottle was charged with 0.14 g (0.34 mmoles) of 70112, 0.97 gms (6.8 mmoles) of methyl iodide, and 7 ml of anhydrous acetonitrile. Heat to 50° C. for 4 days. The quat. Salt Compound No. 192 was isolated by concentrating to 1 cc acetonitrile and then precipitating with diethyl ether. Patent; G.D. Searle and Company; US6107494; (2000); (A1) English View in Reaxys 6 : Preparation 6 Preparation 6 Starting Material GE V A solution of Burgess reagent (3.5 mmol) in dry CH2 Cl2 (3 ml) is added dropwise to a stirred solution of starting material GE IV (1 mmol) in dry CH2 Cl2 (15 ml) and TEA (1.5 mmol) at room temperature. Stirring is continued overnight at this temperature, thus the reaction mixture is concentrated to a small volume under reduced pressure. Addition of Et2 O (35 ml) produced the precipitation of a solid which is used as such in the next step. The solid from the previous step is dissolved in dioxane (22 ml) and 1M NaOH (8.8 ml) is added portion-wise over 24 hours at room temperature with stirring. Patent; BioSearch Italia, S.p.A.; US6008225; (1999); (A1) English View in Reaxys Preparation of STR516 Example 1435 Preparation of STR516 1,4-Diazabicyclo(2.2.2)octane (0.0785 g, 0.700 mmol) and acetonitrile (1.0 mL) were combined in a 10 mL roundbottom flask. The reaction flask was purged with N2, equipped with magnetic stirrer, and heated to 37° C. A solution of the product of Example 1434 (0.250 g, 0.432 mmol) in acetonitrile (2.50 mL) was added. After 2.5 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0200 g, 0.178 mmol) was added. After 64 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0490 g, 0.437 mmol) was added. After 24 hrs, the reaction mixture was cooled to R.T. and concentrated in vacuo. The crude product was dissolved in acetonitrile (2.0 mL) and precipitated with ethyl ether (10.0 mL). The precipitate was filtered to yield a white solid. This trituration method was repeated, followed by concentrated in vacuo to give a white solid (0.185 g, 62percent). mp 218.0-225.0° C.; 1 H NMR (CD3 OD) δ 0.90 (m, 6H), 1.05-1.55 (m, 10H), 1.16 (t, J=6.6 Hz, 2H), 1.78 (m, 1H), 2.12 (m, 3H), 2.76 (s, 6H), 3.10 (m, 2H), 3.17 (t, J=7.2 Hz, 6H), 3.30-3.50 (m, 8H), 4.10 (s, 1H), 4.21 (t, J=5.4 Hz,

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2H), 5.31 (s, 1H), 6.10 (s, 1H), 6.55 (d, J=7.2 Hz, 1H), 7.25 (d, J=6.9 Hz, 1H), 7.33-7.42 (m, 2H), 7.56 (s, 1H), 7.76 (d, J=9.0 Hz, 1H). HRMS. Calc'd for C36 H55 N4 O5 SCl: 655.3893. Found: 655.3880. Patent; G.D. Searle and Company; US6107494; (2000); (A1) English View in Reaxys Preparation of: STR513 EXAMPLE 1435 Preparation of: STR513 1,4-Diazabicyclo(2.2.2)octane (0.0785 g, 0.700 mmol) and acetonitrile (1.0 mL) were combined in a 10 mL roundbottom flask. The reaction flask was purged with N2, equipped with magnetic stirrer, and heated to 37° C. A solution of the product of Example 1434 (0.250 g, 0.432 mmol) in acetonitrile (2.50 mL) was added. After 2.5 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0200 g, 0.178 mmol) was added. After 64 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0490 g, 0.437 mmol) was added. After 24 hrs, the reaction mixture was cooled to R.T. and concentrated in vacuo. The crude product was dissolved in acetonitrile (2.0 mL) and precipitated with ethyl ether (10.0 mL). The precipitate was filtered to yield a white solid. This trituration method was repeated, followed by concentrated in vacuo to give a white solid (0.185 g, 62percent). mp 218.0-225.0° C.; 1 H NMR (CD3 OD) δ 0.90 (m, 6H), 1.05-1.55 (m, 10H), 1.16 (t, J=6.6 Hz, 2H), 1.78 (m, 1H), 2.12 (m, 3H), 2.76 (s, 6H), 3.10 (m, 2H), 3.17 (t, J=7.2 Hz, 6H), 3.30-3.50 (m, 8H), 4.10 (s, 1H), 4.21 (t, J=5.4 Hz, 2H), 5.31 (s, 1H), 6.10 (s, 1H), 6.55 (d, J=7.2 Hz, 1H), 7.25 (d, J=6.9 Hz, 1H), 7.33-7.42 (m, 2H), 7.56 (s, 1H), 7.76 (d, J=9.0 Hz, 1H). HRMS. Calc'd for C36 H55 N4 O5 SCl: 655.3893. Found: 655.3880. Patent; G.D. Searle and Company; US5994391; (1999); (A1) English View in Reaxys General hydrogenation yielding final mimetics as illustrated in FIG. 5 General hydrogenation yielding final mimetics as illustrated in FIG. 5 Benzyl protected fucopeptides were dissolved in a mixture of EtOH/THF/H2 O (5:1:1), 10percent Pd/C as hydrogenation catalyst was added and the suspension was purged several times with hydrogen. Vigorous stirring under H2 (1 atm) was continued for 3-4 h. The mixture was filtered through celite (washed with EtOH or EtOH/H2 O) and concentrated in vacuo. case a) carboxylates: the residual colorless oil or solid was dissolved in MeOH and fractional precipitated by addition of Et2 O. Patent; The Scripps Research Institute; US6111084; (2000); (A1) English View in Reaxys 1.c : (c) Hydrazine monohydrate (1.25 mL) and 8-chloro-10,11-dihydro-10[(1,3-dihydro-1,3-dioxo-2H -isoindol-2-yl)acetyl]-dibenz[b,f][1,4]-oxazepine (5.00 grams) were refluxed in absolute ethanol (125 mL) for 4 hours. The resulting mixture was filtered hot, and the collected solid was rinsed twice with ethanol, and then with hot methylene chloride. The filtrate and rinses were combined, evaporated in vacuo, and purified by flash chromatography through silica gel 60 (300 mL) using 95:5:0.5 chloroform:methanol:ammonium hydroxide. Trituration of the purified product with ethyl ether/hexane yielded the title compound as a white solid. Yield: 2.91 grams (84percent). Mp: 108°-109° C. Patent; G. D. Searle and Co.; US5212169; (1993); (A1) English View in Reaxys 19 : Preparation 19 Deprotection of the Cbz-protecting group is carried out just before usage of the serinamide. A suspension of the above prepared N-Cbz-L-serinamide (5.0 g, 11.52 mmol) and 10percent palladium on charcoal (500 mg) in methanol (90 ml) is hydrogenated at room temperature and atmospheric pressure in the presence of 20percent methanolic HCl (4.6 ml) for 1 hour. The catalyst is filtered off, washed over the filter with methanol (2*100 ml) and the solvent evaporated to dryness under reduced pressure. Trituration of the waxy solid with Et2 O yielded the expected serinamide hydrochloric salt as a white powder. Patent; Biosearch Italia S.p.A.; US6143739; (2000); (A1) English View in Reaxys

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58.B : EXAMPLE 58 Part B: A solution of 2.5 g of the compound from part A in 20 mL 4N HCl-dioxane and stirred for 1 hour at room temperature. Concentration in vacuo followed by triturationwith Et2 O yielded 2.2 g white solid. The product was vacumn dried over P2 O5 to yield 2.1 g final product. Patent; G.D. Searle and Co.; US6143788; (2000); (A1) English View in Reaxys R.23 : Production of 2-(2-furyl)benzyl chloride Thionyl chloride (73 microliters) was added, and under ice cooling, the mixture was stirred for 3 hours. After the reaction, the reaction mixture was washed with a saturated aqueous solution of sodium chloride and 5percent sodium hydrogen carbonate to give an ethyl ether solution of the captioned compound. It was used directly in the reaction of Example 58. Patent; Banyu Pharmaceutical Co., Ltd.; US5234946; (1993); (A1) English View in Reaxys b : b) 234 g of the product obtained under a) was mixed with 468 g water, 234 g isopropanol and 169 g hydrogen bromide (48percent wt) and heated under nitrogen to 70° C. 58 g propylene oxide was added in the course of a few minutes, causing an increase in the pressure from 1.64 bar to 2.03 bar. After 2 hours the pressure had become constant at 1.85 bar. The crude product was worked up by flashing off the solvent followed by 2* desalting in isopropanol. Non-polar organics were removed by dissolving the sample in water, raising the pH to 14 and extracting the water layer twice with diethylether. After readjustment of the pH with hydrogen bromide the solution was subjected to evaporation to dryness. A polar organic impurity, propylene glycol, was removed by slurrying with diethylether. The final amount of propylene glycol in the otherwise pure product (yield 145 g) amounted to less than 3percent mole. Patent; Shell Oil Company; US6152993; (2000); (A1) English View in Reaxys [Au(d3pype)2 ]Cl [Au(d3pype)2 ]Cl d3pype (0.4 g, 0.99 mmol) was dissolved in DMSO (20 mL) under an atomosphere of argon. Bu4 NAuCl2 (0.236 g, 0.46 mmol was added as a solid and the resulting yellow solution was stirred overnight. In an attempt to precipitate the product Et2 O (10 mL) was added but no precipitate formed after several hours refrigeration, but instead the solution settled into two layers. To this mixture toluene (30 mL) was added and the clear pale yellow solution cooled to -20° C. for 24 hrs during which time the desired compound precipitated as a light yellow solid and was collected by filtration. Patent; Griffith University; US6159957; (2000); (A1) English View in Reaxys 6.C : (E)-3-[4-((2-n-Butyl-5-oxo-4-spirocyclopentane-2-imidazolin-1-yl)methyl)phenyl]-2-phenylacrylic acid. STR25 A solution containing 1.93 g of the aldehyde prepared in the preceding stage, 850 mg of phenylacetic acid, 6 ml of acetic anhydride and 6 ml of triethylamine are brought to reflux for 35 minutes. The reaction mixture is cooled in an ice bath and then 10 ml of concentrated hydrochloric acid and then 100 ml of water are slowly added at 0° C. The aqueous phase is extracted with 3 times 50 ml of DCM, the organic phases are combined, washed with 100 ml of water, dried over sodium sulphate, filtered and the filtrate is concentrated. The gum obtained is taken up with 100 ml of ethyl ether and is extracted 3 times with 50 ml of 10percent sodium hydroxide. The alkaline phase is acidified to pH 3-4 by the addition of concentrated hydrochloric acid and is then extracted 3 times with 50 ml of ethyl acetate. The extract is dried over sodium sulphate, filtered and concentrated. The product obtained is purified by chromatography on silica by eluding with AcOEt/toluene/AcOH (2/8/0.3; v/v/v). An oil (m=850 mg) is obtained which precipitates on triturating in ether. m.p.=153° C.

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NMR: 0.75 ppm: t: 3 H: CH3 (nBu), 1.20 ppm: sext: 2 H: CH3 --CH2 --, 1.40 ppm: m: 2 H: CH3 --CH2 --CH2 --, 150-1.90 ppm: m: 8 H: cyclopentane, 2.2 ppm: t: 2 H: CH3 --CH2 --CH2 --CH2 --, 4.60 ppm: s: 2 H: CH2 --C6 H4, 6.90-7.70 ppm: m: 10 H: aromatic and 1 H ethylenic Patent; Elf Sanofi, A French Corp.; US5274104; (1993); (A1) English View in Reaxys 2.d : Preparation of the Complex [Ru (DA-bpy)2 (NPM-bpy)](PF6)4 In a second step 0,028 g (0.050 mmol) of NPM-bpy was dissolved in 5 ml water and then 10 ml of dimethylformamide and 0,025 g (0,043 mmol) of ruthenium bis(4,4'-bisamino-2,2'-bipyridine) Cl2 (hereinafter referred to as Ru(DAbpy)2 Cl2) were added and the mixture heated at reflux for at least 4 hours at about 140°-150° C. under a nitrogen atmosphere at atmospheric pressure. After having allowed the mixture to cool to room temperature, the solution was filtered and the solvent concentrated to a quarter of the original volume. The complex was then precipitated by addition of diethylether, the complex was isolated by filtration and dissolved in 10 ml water; the complex was precipitated in the form of its hexafluorophosphate salt by addition of an aqueous solution of potassium hexafluorophosphate; it was isolated by filtration, washed with diethylether and dried under a high vacuum. Patent; Asulab S.A.; US5410059; (1995); (A1) English View in Reaxys 2 : Preparation of N-[(4R,4S)-6-phenyl-2,4-dihydro-1H-imidazo[1,2-α][1,4benzodiazepin-4-yl]-N'-[3-methylphenyl]-urea The analytical product was obtained as a white solid via flash chromatography on silica gel (chloroform-methanol, 88:12) followed by trituration of the chromatographed product with ethyl ether: m.p. 147° C.(d). 1 H-NMR (CDCl3): Consistent with structure and confirms solvate form; HPLC:>91percent pure at 214 nM; Rf =0.3 (CHCl3 -CH3 OH; 9:1) FAB MS: 410 (M+ +H); Elem. Anal. calc'd for C25 H23 N5 O 0.15CHCl3 0.75CH3 OH: Calc'd: C, 68.90; H, 5.84; N, 15.52. Found: C, 68.92; H, 5.67; N, 15.18. Patent; Merck and Co., Inc.; US5439906; (1995); (A1) English View in Reaxys 6 : EXAMPLE 6 STR24 EXAMPLE 6 STR24 To a stirred solution of the bicyclic β-keto ester 4 (116.7 mg, 0.335 mmol) in dry THF (1.4 mL) at -78° C. under N2 was added diisopropylamine (51.6 μL, 0.369 mmol, 1.1 eq). The resultant yellow mixture was stirred for 10 minutes before trifluoromethanesulfonic anhydride (62 μL, 0.369 mmol, 1.1 eq) was added. After 15 minutes the reaction mixture was treated sequentially with anhydrous N-methyl-2-pyrrolidinone (1.4 mL), the (MeCN)2 PdCl2 catalyst (3.6 mg, 1.4*102 mmol, 5.0 mol percent), the aryl-stannane 7 (100 mg, 0.279 mmol) and diisopropylammonium chloride (38 mg; 0.279 mmol). The low temperature bath was then removed and the reaction vessel was placed in a warm water bath to quickly reach ambient temperature. The resulting solution was stirred for 20 minutes at ambient temperature. The reaction was then poured into EtoAc and washed with water (4*) and brine. The organic layer was dried (Na2 SO4), filtered, and evaporated in vacuo. The residue was dissolved in CH2 Cl2 and precipitated with Et2 O to provide carbapenem 8. 1

H NMR (400 MHz, D6 DMSO) δ1.19 (d, J=6.0 Hz, 3H) 3.35 (1/2 ABX, obscured by H2 O peak from DMSO, 1H),

3.49-3.50 (m, 1H), 3.73 (1/2 ABX, JAB =18.9 Hz, JAX =8.6 Hz, 1H), 4.00-4.06 (m, 1H), 4.31-4.35 (m, 1H), 5.22 (ABq, JAB =13.6 Hz, ΔυAB =49.8 Hz, 2H), 7.32 (d, J=8.5 Hz, 2H), 7.68-7.72 (m, 2H), 7.83 (d, J=8.8 Hz, 2H), 7.93-7.95 (m, 1H), 8.58 (d, J=8.7, 1H), 8.62-8.64 (m, 1H), 8.80 (s, 1H), 9.08 (s, 1H); I.R. (KBr) 3520, 1750, 1720, 1600, 1510 cm-1. Patent; Merck and Co., Inc.; US5336674; (1994); (A1) English View in Reaxys R.1 : Preparation of (E,E,E)-2-(6,6-dimethyl-2-hepten-4-ynyl)-8-[3-[3-thienyl)phenyl]-2,7-octadienic acid methyl ester REFERENTIAL EXAMPLE 1 Preparation of (E,E,E)-2-(6,6-dimethyl-2-hepten-4-ynyl)-8-[3-[3-thienyl)phenyl]-2,7-octadienic acid methyl ester

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44.6 g of 4-cyanobutyltriphenylphosphonium bromide is dissolved in 250 ml of dimethylformamide, 4.2 g of 60percent oily sodium hydride is added under ice cooling and stirring, then mixture is stirred at that temperature for 30 minutes, 18 g of 3-(3-thienyl)benzaldehyde is added, and the mixture is stirred at room temperature for further 20 hours. The reaction solution is diluted with water, acetic acid is added for neutralization, and then the solvent is distilled off under reduced pressure. The residue is led to two liquid phases using a system of water and ethyl ether, the organic layer is taken, washed with saturated saline and dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. Patent; Banyu Pharmaceutical Co., Ltd.; US5444084; (1995); (A1) English View in Reaxys I.38.A : Reference Example 11 (A) With cooling at -78° C., ammonia gas was blown into a three neck flask to yield 600 ml of liquid ammonia. At -78° C., 19.0 g of sodium amide was added to the flask and stirred for 10 minutes at the same temperature, followed by gradual addition of 40 ml of n-butyronitrile in a dropwise manner and subsequent 10 minutes of stirring at -78° C. A 40 ml portion of ethyl formate was gradually added in a dropwise manner to the above reaction solution and the mixture was stirred for 1 hour at -78° C. With stirring, the reaction solution was warmed on a 40° C. water bath to distill off ammonia. The resulting residue was added to 150 ml of ice water and adjusted to a pH value of less than 1 with 6N hydrochloric acid. After extracting twice with 30 ml of ethyl ether, the resulting ether layers were combined and mixed with 100 ml of ethanol. Patent; Yamanouchi Pharmaceutical Co., Ltd.; US5475114; (1995); (A1) English View in Reaxys 1.b : b Trituration of the foam with ethyl ether produced the title product as a white solid; m.p.=147°-148° C. TLC (75:25ethyl acetate:hexanes) Rf =0.56; [α]D=- 143.2° (c=0.6, chloroform). Patent; Bristol-Myers Squibb Company; US5508272; (1996); (A1) English View in Reaxys 6.b : a) b) Preparation of the N-CBzO derivative of the teicoplanin amide compound The condensation of the above obtained N-benzoyloxycarbonyl starting material with the selected amine is carried out in DMF (HPLC, method c) in the presence of DPPA under the same reaction conditions as described in example 1. The N-CBzO-teicoplanin amide compound is obtained as a solid which precipitates from the reaction mixture by adding ethyl ether. Patent; Gruppo Lepetit S.p.A; US5521155; (1996); (A1) English View in Reaxys 7.a : a) a) Preparation of the N-tert-butoxycarbonyl protected teicoplanin starting material (N-t-BOC-ST) A mixture of 4 mmol of the selected teicoplanin starting material 2 ml (14.5 mmol) of TEA and 2 g (~7 mmol) of tertbutyl 2,4,5-trichlorophenylcarbonate in 100 ml of DMF is stirred 24 h at room temperature. On adding ether (900 ml) a solid separates which is collected and re-dissolved in a mixture (11) water:methanol 7:3. The resulting solution is brought to pH 3.5 with 1N HCl, then extracted with ether (500 ml). The aqueous layer is extracted again with n-butanol (1 l). The butanolic layer is washed with water (2*500 ml) and concentrated to a small volume under vacuum at 35° C. By adding ethyl ether a solid is precipitated which is collected, washed with ether and dried in vacuo at 40° C. overnight, yielding (the yields are always higher than 90percent) the N-t-BOC protected teicoplanin starting material pure enough (HPLC titre>90percent, method c) for the next step. Patent; Gruppo Lepetit S.p.A; US5521155; (1996); (A1) English

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View in Reaxys 7.c : a) c) Preparation of the teicoplanin amide derivative of the title A solution of 1 mmol of N-t-BOC-teicoplanin amide in 40 ml of 100percent trifluoroacetic acid (TFA) is stirred 10-20 min at 5° C., afterwards the solvent is evaporated under vacuum at 25° C. The oily residue is triturated with ether, then collected and re-dissolved in 150 ml of methanol. Silanized silica gel (0.063-0.2 mm 5 g Merck) is added and the solvent is evaporated under vacuum at 40° C. The residue is put at the top of a column containing the same silanized silica gel (150 g) prepared in the mixture water:acetonitrile 95:5 (v/v). Column chromatography is carried out substantially according to the procedure described in example 4 c. More particularly, the column is developed with a linear gradient elution from 5percent CH3 CN in 0.001N HCl to 30percent CH3 CN in H2 O in the case of compound 9, with a linear gradient elution from 10percent CH3 CN in 0.001N HCl to 40percent CH3 CN in H2 O in the case of compound 14 and with a linear gradient from 20percent CH3 CN in 0.001N HCl to 55percent CH3 CN in water in the case of compound 22. The flow rate is 120 ml/h and the time is 15 h. Fractions of 12 ml are collected, monitored by HPLC and worked up substantially as already described in example 4c. Fractions containing the pure compounds of the title are pooled and to the resulting solution n-butanol (v/v) and 1N HCl (2 ml) are added. After concentration to a small volume under vacuum at 40° C. the title compound is obtained (as the corresponding di-hydrochloride, except for compound no. 25 which is recovered as mono-hydrochloride) by precipitating with ethyl ether from the butanolic phase, washing and drying overnight in vacuo at 40° C. Patent; Gruppo Lepetit S.p.A; US5521155; (1996); (A1) English View in Reaxys 8 : Preparation of the trifluoroacetate salts of teicoplanin compound amides 18-25 EXAMPLE 8 Preparation of the trifluoroacetate salts of teicoplanin compound amides 18-25 A teicoplanin compound amide (amides 18-25) is dissolved (1 g in 300 ml) in a mixture water:acetonitrile, 8:2 (v/v). The resulting solution is brought td pH 8.5 with 0.1N NaOH and extracted (v/v) with n-butanol. The organic layer is separated, washed with water (v/v) and concentrated to a small volume. On adding ether, the solid which separates is collected, washed with ether and dried overnight in vacuo at 35° C., yielding the corresponding free base which is re-dissolved in TFA (1 g in 10 ml) and precipitated with ethyl ether (100-200 ml). After collecting the solid by filtration, washing with ether and drying in vacuo 24 h at room temperature, the title compounds are obtained (18-24, di-trifluoroacetates and 25 trifluoroacetate). Patent; Gruppo Lepetit S.p.A; US5521155; (1996); (A1) English View in Reaxys R.27 : Reference Example 27 Reference Example 27 cis-4-(2-Diethylaminoethyl)-4-hydroxymethyl-7-methoxy-3,4-dihydro-2H-1,5-benzoxathiepin-3-ol (0.7 g) obtained in Reference Example 25 was dissolved in pyridine (10 ml). Acetic arthydride (6 ml) was added and the mixture was allowed to stand at room temperature for 3 hours. The reaction mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with an aqueous solution of sodium hydrogencarbonate and water, and dried. The solvent was evaporated under reduced pressure to give 0.66 g of colorless, oily cis-3-acetoxy-4-acetoxymethyl-7-methoxy-4-(2-diethylaminoethyl)-3,4-dihydro-2H-1,5-benzoxathiepine. Recrystallization of the hydrochloride of the obtained compound from ethanol-ethyl ether yielded white crystals, melting point 177°-179° C. Elemental analysis as C21 H31 NO6 S.HCl. 1/5H2 O Calculated: C 54.19; H 7.01; N 3.06 Found: C 54.27; H 7.05; N 3.06 Patent; Senju Pharamceutical Co., Ltd.; US5538974; (1996); (A1) English View in Reaxys 247 : 4-(6-Fluoro-1H-indazol-3-yl)-1-[2-(2,3-dihydro-4-methyl-1H-isoindol-2-yl)ethyl]piperazine difumarate EXAMPLE 247

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4-(6-Fluoro-1H-indazol-3-yl)-1-[2-(2,3-dihydro-4-methyl-1H-isoindol-2-yl)ethyl]piperazine difumarate To a stirred solution of 2-[2-[4-(6-fluoro-1H-indazol-3-yl)-1-piperazinyl]ethyl]-3-methylphthalimide (5.4 g, 13.3 mmol) in THF (200 ml) under N2 was added, dropwise, LAH (30.0 ml of a 1.0M LAH/THF solution). After complete addition, the reaction was stirred at reflux for 4.5 hours. The reaction was cooled in an ice bath and H2 O (2 ml) was carefully added followed by 1.0M NaOH (3 ml). The mixture was filtered and the filtrate was concentrated to yield 5.0 g of a brown oil. Trituration of the oil with Et2 O produced a white solid that was isolated by filtration to give 2.1 g of a white solid. Patent; Hoechst Roussel Pharmaceuticals, Inc.; US5605913; (1997); (A1) English View in Reaxys 1 : CH3 O--(CH2 CH2 O)n --CH2 CH2 CO2 --NHS Yield of acid 14.0 g. NMR (d6 -DMSO): 2.43 ppm (t, 4H, --CH2 --COOH); 3.21 ppm (s, --OCH3), 3.50 ppm (s, --OCH2 CH2 O--). M-PEG propionic acid (3.4 g, 1 mmol) was dissolved in dichloromethane (20 ml) and N-hydroxysuccinimide (2.1 mmol) was added. The solution was cooled to 0° C., a solution of dicyclohexylcarbodiimide (2.1 mmol) in 4 ml dichloromethane was added dropwise, and the solution was stirred at room temperature overnight. The reaction mixture was filtered, concentrated, and precipitated by addition to diethylether. Yield of final productproduct: 3.3 g. NMR (d6 -DMSO): 2.81 ppm (s, 8H, NHS); 2.92 ppm (t, 4H, --CH2 --COO--); 3.21 ppm, (s, --OCH3), 3.5 ppm (s, --OCH2 CH2 O--). Patent; Shearwater Polymers, Inc.; US5672662; (1997); (A1) English View in Reaxys 2.c : 2. 2c) Partial sequence Boc-L-Asn-L-Ser(Bzl)-L-Leu-NH-NH2 (C). 3 g of Boc-L-Asn-L-Ser-(Bzl)-L-Leu OEt is dissolved in 20 ml of CH3 OH, 10 ml of 80percent NH2 --NH2 --H2 O is added and the mixture is left for 14 hours at ambient temperature. It is then precipitated with ethyl ether, the precipitate is washed with ethyl ether and recrystallized from a mixture of CH3 OH-AcOEt-ethyl ether. 2.5 g of expected product is obtained (C). Patent; Milhaud; Gerard; US5656723; (1997); (A1) English View in Reaxys 73 : Preparation of BCH2820 and 2821 (1'S,2'R,3'S,5'R,1R,3R) and (1'S,2'R,3'S,5'R,1S,3S)-1-(3-trifluoroacetamido-2-hydroxy-1-methyl tetrahydropyran -5-yl)methyl-3-methylketone-5,10-dioxo-3,4,5,10-tetrahydro-1Hnaphtho[2,3-C]pyran. STR156 Step 1: After 20 minutes of stirring, the reaction was quenched with NaHCO3 sat (10 ml) and extractions were done with Et2 O (2*10 ml). The combined organic layers were washed with NaCl sat(15 ml) and dried (MgSO4). Flash chromatography of the residue (hexane:acetone; 7:3) gave 46 mg of a stereoisomer mixture of product III (68percent yield). Patent; BioChem Pharma Inc.; US5606037; (1997); (A1) English View in Reaxys 2.2 : Synthesis of 1-((2R,5R)-2,5-Dimethylpyrrolidinylmethyl)-2-diphenylphosphinonaphthalene (Ib) 2) 1-((2R,5R)-2,5-Dimethylpyrrolidinylamido)-2-diphenylphosphinylnaphthalene: A 50 ml two-necked eggplant flask containing 355.4 mg of N-(1-naphthoyl)-(2R,5R)-2,5-dimethylpyrrolidine was purged with nitrogen, and THF and 0.2 ml of tetramethylethylenediamine were added to the flask, followed by stirring. After cooling to -78° C., sec-butyl lithium was slowly added thereto dropwise, followed by stirring for 1 hour. Chlorodiphenylphosphine was slowly added dropwise at -78° C., and the mixture was stirred for 0.5 hour. The reaction was stopped by addition of 2N HCl. An attempt to extract the reaction mixture with ethyl ether resulted in precipitation of insoluble matter. As a next attempt, the reaction mixture was extracted with chloroform. Since the aqueous layer was found turbid, it was again extracted with ethyl ether. The ethyl ether layer and the chloroform layer were combined, washed successively with 2N sodium carbonate and water, dried over anhydrous magnesium sulfate, and dried under reduced pressure.

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Patent; Takasago International Corporation; US5756760; (1998); (A1) English View in Reaxys 115.ii : Method ii Method ii By substantially following the procedure of Example 126d (Method ii) and using 117 g (500 mmole) of 2-bromo-4'chloroacetophenone and 100 g of 2,2,2-trichloroethylchloroform in place of methyl chloroformate one obtains 158 g of the title compound, an oil. c: 2-(N-methyl-N-(2,2,2-trichloroethoxycarbonyl)amino)-1-(4-chlorophenyl)prop-2-enone To 21.5 g (60 mmole) of 2-(N-methyl-N-(2,2,2-trichloroethoxycarbonyl)amino)-4'-chloroacetophenone (Example 115b) in 100 ml of 1-propanol was added 9.7 g (120 mmole) of 37percent formalin, 1 g of piperidine and 0.7 g of acetic acid. The mixture was refluxed for four hours, concentrated in vacuo, partitioned between diethyl ether and water, washed with brine, dried over anhydrous magnesium sulfate, and reconcentrated under vacuo, yielding 20 g of the title compound, an oil. d: N-(4-trifluoromethylphenyl)-3-(4-chlorophenyl)-4-(N-methyl-N-(2,2,2-trichloroethoxycarbonyl)amino)-4,5-dihydro-1H-pyrazole-1-carboxamide To 35.7 g (96 mmole) of 2-(N-methyl-N-(2,2,2-trichloroethoxycarbonyl)amino)-1-(4-chlorophenyl)-prop-2-enone (Example 115c) in 60 ml of methanol was added 5.8 g (115 mmole) of hydrazine monohydrate. The mixture was refluxed for ten minutes, concentrated in vacuo, partitioned between diethyl ether and water, washed with brine, dried over anhydrous magnesium sulfate, and filtered. This yielded a diethyl ether solution of 3-(4-chlorophenyl)-4-(N-methyl-N-(2,2,2-trichloroethoxycarbonyl)amino)-4,5dihydro-1H-pyrazole which was not isolated. Patent; Rohm and Haas Company; US5798311; (1998); (A1) English View in Reaxys 1 : 1d For Grignard reaction, a solution of 26.7 g of 4-chloro-1-(tert-butyldimethylsilyloxy)-butane in 24 ml of tetrahydrofuran is added in drops to 5.76 g of magnesium at 25° C. under argon, a crystal of iodine was added and stirred for 30 minutes at 60° C. Then, it is diluted with 74 ml of tetrahydrofuran. The solution of 4.6 g of the aldehyde, produced above, in 35 ml of tetrahydrofuran is added in drops to 23 ml of this Grignard solution under argon at -70° C., and it is stirred for 30 minutes at -70° C. It is mixed with saturated ammonium chloride solution, extracted three times with diethyl ether, the organic phase is shaken with brine, dried on sodium sulfate and concentrated by evaporation in a vacuum. The residue is chromatographed on silica gel. With hexane/diethyl ether (9+1), first obtained is 720 mg of the 5R-configured diastereomer alcohol and obtained as polar component is 3.6 g of the 5-configured diastereomer alcohol (title compound). IR: 3580, 2923, 2850, 1728, 1245, 990, 965, 835 cm-1. Patent; Schering Aktiengesellschaft; US5783602; (1998); (A1) English View in Reaxys 247 : 4-(6-Fluoro-1H-indazol-3-yl)-1-2-(2,3-dihydro-4-methyl-1[H-isoindol-2-yl)ethyl]piperazine difumarate EXAMPLE 247 4-(6-Fluoro-1H-indazol-3-yl)-1-2-(2,3-dihydro-4-methyl-1[H-isoindol-2-yl)ethyl]piperazine difumarate To a stirred solution of 2-[2-[4-(6-fluoro-lH-indazol-3-yl)-1-piperazinyl]ethyl]-3-methylphthalimide (5.4 g, 13.3 mmol) in THF (200 ml) under N2 was added, dropwise, LAH (30.0 ml of a 1.0 M LAH/THF solution). After complete addition, the reaction was stirred at reflux for 4.5 hours. The reaction was cooled in an ice bath and H20 (2 ml) was carefully added followed by 1.0M NaOH (3 ml). The mixture was filtered and the filtrate was concentrated to yield 5.0 g of a brown oil. Trituration of the oil with Et2 O produced a white solid that was isolated by filtration to give 2.1 g of a white solid. Patent; Hoechst Marion Roussel, Inc.; US5776963; (1998); (A1) English View in Reaxys 26 mg (63%)

24 : EXAMPLE 24 STR124 EXAMPLE 24 STR124 To a stirred solution of 10 (33.0 mg, 0.053 mmol) in CH2 Cl2 (1.0 mL) cooled to -78° C. under N2 was added collidine (8.3 μL, 0.063 mmol, 1.2 equiv.) followed by trifluoromethanesulfonic anhydride (9.7 μL, 0.058 mmol, 1.1 equiv.). After 35 minutes 4-methyl-1,2,4-triazole (9.6 mg, 0.116 mmol, 2.2 equiv.) was added.

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The reaction vessel was warmed to -30° C. and stirred for 30 minutes before being poured into EtOAc containing some Et2 O. The organic layer was washed with H2 O (4*), dried (Na2 SO4), filter and evaporated in vacuo. The residual solid was dissolved in CH2 Cl2 and precipitated using Et2 O (2*) to afford 26 mg (63percent) of compound 26, a yellowish solid. 1 H NMR (400 MHz, CDCl ) δ 0.13 (s, 9H), 1.28 (d, J=6.2 Hz, 3 H), 3.26 (1/2 ABX, J 3 AB =18.6 Hz, JAX =10.2 Hz, 1H), 3.38 (dd, J=6.1, 3.0 Hz, 1H), 3.45 (1/2 ABX, JAB =18.3 Hz, JAX =9.9 Hz, 1H), 4.17 (s, 3H), 4.26 (m, 1H), 4.36 (t, J=9.8 Hz, 1H), 5.18 (ABq, JAB =13.2 Hz, ΔυAB =65.3 Hz, 2 H), 5.61 (s, 2 H), 7.33-7.44 (complex m, 6H), 7.75 (d, J=8.4 Hz, 1H), 7.86(s, 1H), 7.89 (d, J=8.8 Hz, 2 H), 8.06 (d, J=8.4 Hz, 1H), 8.74 (s, 1 H). IR(CHCl3) 1775, 1725, 1601 cm-1. Patent; Merck and Co., Inc.; US5153186; (1992); (A1) English View in Reaxys 2 : Preparation of N-(4R,4S)-6-phenyl-2,4-dihydro-1H-imidazo[[1,2-a][1,4]benzodiazepin-4-yl]-N'-[3-methylphenyl]-urea The analytical product was obtained as a white solid via flash chromatography on silica gel (chloroform-methanol, 88:12) followed by trituration of the chromatographed product with ethyl ether: m.p. 147° C.(d). 1 H-NMR(CDCl ): 3 Consistent with structure and confirms solvate form; HPLC: >91percent pure at 214 nM; Rf =0.3(CHCl3 --CH3 OH;9:1) FAB MS: 410(M+ +H); Elem. Anal. calc'd for C25 H23 N5 O.0.15CHCl3.0.75CH 3 OH: Calc'd: C,68.90; H,5.84; N,15.52. Found: C,68.92; H,5.67; N,15.18. Patent; Merck and Co., Inc.; US5834464; (1998); (A1) English View in Reaxys 4.B : STEP B STEP B Reduction of a sample of the mixture of didehydroindanylaetates (0.48g) from step A was effected by hydrogenation, under a slight positive pressure of hydrogen, in absolute ethanol (50ml) in the presence of a catalytic quantity of 5percent palladium on charcoal (approximately 10g). Removal of solid by filtration through hiflow and concentration of the filtrate under reduced pressure gave an oil (0.34g). Purification of the oil by preparative thin layer chromatography (silica/hexane-diethylether, 7:3) gave compound 4, ethyl (RS)-6-(2-chloro-6-fluoro-4-trifluoromethylphenoxyindan-1-ylacetate), as a pale yellow oil (0.33g,68percent). δH (CDCl3) 1.20(t)3H; 1.80(m)lH; 2.40(m)2H; 2.70(dd)1H; 2.90(m)2H; 3.50(m)1H; 4.10(q)2H; 6.70(m)2H; 7.10(d)1H; 7.40(dd)1H; 7.55(broad s)1H. Patent; Imperial Chemical Industries PLC; US5167696; (1992); (A1) English View in Reaxys A method according to claim 2 wherein the solvent is selected from the group consisting of acetone, heptane, toluene, ... isopropanol-water, tetrahydrofuraii-water, ethanol-water, ethyl ether, amyl acetate, isopropyl acetate-methanol isopropyl butyrate, isopropylamine, and ... Patent; Abbott Laboratories; US5844105; (1998); (A1) English View in Reaxys

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68.b : 3(RS)-[2-(Tricylo[3.3.1.13,7 ]-dec-1-yl)ethoxycarbonyl]-L-α-aminobutyryl-N-[3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)]-L-prolinamide (Formula Ib, R1 =CH(CH3)CH3, R2 =CH3 CH2 -, R3 =(1-adamantyl)-CH2 CH2, R4 =H, A=OCO, n=1) b. 3(RS)-[2-(Tricyclo[3.3.1.13,7 ]-dec-1-yl)ethoxycarbonyl]-L-α-aminobutyryl-N-[3-(1,1,1-trifluoro-4-methyl-2-oxopentyl)]L-prolinamide (Formula Ib, R1 =CH(CH3)CH3, R2 =CH3 CH2, R3 =(1-adamantyl)-CH2 CH2, R4 =H, A=OCO, n=1) Using the method of Example 61c, the product of Example 68a was oxidized to afford, after purification by flash chromatography (Et2 O:hexane (50:50), then (90:10)), the title product (66percent); HPLC, tR =4.64 and 5.63, Col A, H2 O:CH3 CN (25:75), FR=2.0. Analysis calculated for: C28 H42 F3 N3 O5.0.15H 2 O: C, 60.01; H, 7.60. Found: C, 59.76; H, 7.65. Patent; ICI Americas Inc.; US4910190; (1990); (A1) English View in Reaxys 1 : EXAMPLE 1 STR48 EXAMPLE 1 STR48 To a solution of 0.98 g (1.41 mmole) of DNMA--GLU--STA--NHCH2 CH(CH3)CH2 CH3 in 40 ml CH2 Cl2 was added a solution of 0.20 g (1.48 mmole) of HOBT in 1 ml DMF. This solution was cooled to 0°, and a solution of 0.30 g (1.62 mmole) of GLY[CSNHCH3 ].HHr in 10 ml CH2 Cl2 was added followed by 0.23 m1 (1.65 mmole) of Et3 N. 0.31 g (1.48 mmole) of DCC was then added and the mixture stirred and allowed to stand at 3° overnight. The solution was filtered to remove dicyclohexylurea and the DMF was removed under high vacuum. The residue was taken into EtOAc and filtered to remove residual urea. The filtrate was washed with 1 N citric acid, saturated NaCl, saturated NaHCO3, and saturated NaCl. After drying, the solvent was removed under reduced pressure giving a gelatinous solid. The solid was redissolved in warm EtOAc, and precipitated by the addition of Et2 O. The solid precipitate was filtered, washed with Et2 O and dried under reduced pressure giving a solid, 0.93 g. The structure was confirmed by NMR and mass spectroscopy. Calcd. for C45 H59 N5 O5 S (MW 782.07): C, 69.11; H, 7.60; N, 8.95; S, 4.10. Found: C, 69.14; H, 7.90; N, 8.84; S, 4.31. Patent; Warner-Lambert Company; US5034512; (1991); (A1) English View in Reaxys 1 : Preparation of: STR10 10[3-[(ethylamino)methyl]-1-pyrrolidinyl]9-fluoro-2,3-dihydro-3-hydrochloride STR11 STR16 3.6 g (0.0165 mols) of benzothiazine (VI) and 3.57 g (0.0165 mols) of diethylethoxy-methylenmalonate (EMME) are kept under stirring and heated up to 160° C. for 8 hours, distilling off the alcohol as it is formed TLC 1/1 ethyl ether/ petroleum ether). At the end by cooling and diluiting with isopropyl ether, a withish solid (VII) precipitates, which is filtered (25 g). Patent; Mediolanum farmaceutici, S.r.l.; US4923859; (1990); (A1) English View in Reaxys 40 : EXAMPLE 40 STR160 EXAMPLE 40 STR160 A solution of 0.55 g (1.62 mmole) of di-(1-naphthylmethyl)acetic acid, 0.69 g (1.62 mmole) of STR161 and 0.23 g (1.7 mmole) of HOBT in 20 ml DMF was treated with 0.35 g (1.7 mmole) of DCC and stirred at room temperature overnight. The mixture was filtered and the DMF removed under high vacuum. The residue was taken up in EtOAc and washed with 1N citric acid, saturated NaCl, saturated NaHCO3, and saturated NaCl. Drying and removal of the solvent under reduced pressure gave the crude product which was chromatographed on silica gel, eluding with EtOAc. Combining the appropriate fractions gave material which was taken up in CH2 Cl2 and precipitated by addition to Et2 O. The solid was collected to give 0.28 g of product. The structure was confirmed by NMR and mass spectroscopy. Calcd. for C47 H55 N5 O4 (MW 753.95): C, 74.87; H, 7.35; N, 9.29 Found C, 74.47; H, 7.35; N, 9.01.

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Patent; Warner-Lambert Company; US5024994; (1991); (A1) English View in Reaxys 43 : EXAMPLE 43 STR162 EXAMPLE 43 STR162 A solution of 0.92 g (3.7 mmole) of IVA-PHE and 0.53 g (3.89 mmole) of HOBT in 4 ml DMF and 30 ml CH2 Cl2 was cooled to -5° and 0.8 g (3.89 mmole) of DCC added followed by 1.26 g (3.7 mmole) of STR163 The solution was stirred at room temperature overnight, filtered, and the solvent removed under reduced pressure. The residue was taken up in EtOAc and washed with 1N citric acid, saturated NaCl, saturated NaHCO3, and saturated NaCl. The solution was dried, the volume reduced under reduced pressure, and the solution diluted with Et2 O. A precipitate formed which was collected giving the crude product. This was chromatographed on silica gel, eluding with CHCl3 /MeOH (98/2). The product was taken up in CHCl3 and precipitated by the addition of Et2 O. There was obtained 1.04 g of product. The structure was confirmed by NMR and mass spectroscopy. Calcd. for C31 H49 N5 O5 (MW 571.74): C, 65.12; H, 8.64; N, 12.25 Found C, 65.00; H, 8.40; N, 12.21. Patent; Warner-Lambert Company; US5024994; (1991); (A1) English View in Reaxys 9 : EXAMPLE 9 EXAMPLE 9 35.4 g of 2,4,5-trifluoroisophthalonitrile was added to 150 ml of 60percent sulfuric acid and the mixture was heated under reflux for 5 hours. As the reaction proceeded, crystallization occurred. After the reaction, the reaction mixture was cooled to room temperature and the crystal was separated by filtration. The filtrate was extracted 5 times with 100 ml of ethyl ether each and the crystal was dissolved in the ethyl ether extracts. The resulting ethyl ether solution was washed several times with 10 ml of a saturated solution of sodium chloride. Patent; SDS Biotech K.K.; US4925966; (1990); (A1) English View in Reaxys (C10) STR41 On adding But NC (ca 6 mg, 0.07 mmol) in THF (1 mL) to a solution of compound (A1) (50 mg, 0.07 mmol) in THF (2 mL) an immediate lightening in color was observed and removal of volatiles followed by addition Et2 O (1 mL) yielded the cream microcrystalline product (C10) (51 mg, 0.066 mmol, 91percent). Anal. Calcd. for C37 H49 ClNP2 RhSi2: C, 58.15; H, 6.46; N, 1.83. Found: C, 57.28; H, 5.72; N, 1.79percent. Patent; University of Victoria; US4950798; (1990); (A1) English View in Reaxys 6 : EXAMPLE 6 EXAMPLE 6 A solution of 2-chloromethyl-3-ethoxycarbonyl-4-(o-methylthiophenyl)-5-methoxycarbonyl-6-methyl-1.4-dihydro pyridine (2.1 g) in EtOH (10 ml) is added dropwise at 0° C. to a solution of N-n-butyl-N-(2-acetylthioethyl)formamide (1.2 g) and NaOH (20percent water solution, 1.2 g). After 3 hours at 0° C., the reaction mixture is warmed at room temperature and stirred for 30 minutes, then it is concentrated in vacuum. After usual work-up, and column chromatography on SiO2 (80 g; eluent AcOEt/Et2 O 70/90) 1.8 g of 2-/2-N-formyl-Nbutylamino)ethylthio/methyl-3-ethoxycarbonyl-4-(o-methylthiophenyl)-5-methoxycarbonyl-6-methyl-1.4-dihydropyridine are obtained as a foam. 1 H-NMR (CDCl ): δ(TMS) 0.1-1.3 (6H, m): 1.5-2.0 (4H, m; 2.1-3.0 (10H, m); 3.20-4.20 (8H, m); 5.10 (1H, s); 6.8 3 (1H, m); 6.9-7.4 (6H, m); 8.1 (1H, s) Patent; Boehringer Biochemia Robin S.p.A.; US5047414; (1991); (A1) English View in Reaxys 19.f : f. This yielded a diethyl ether solution of 3-(4-difluoromethoxyphenyl)-4-(N-methyl-N-(methoxycarbonyl)amino)-4,5-dihydro-1H-pyrazole which was not isolated.

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To this solution was added 2.0 g (10 mmole) of 4-trifluoromethoxyphenyl isocyanate. Patent; Jacobson; Richard M.; US5109014; (1992); (A1) English View in Reaxys 3.a : Erythro-5,6-Dimethoxy-2-[2-(4-hydroxyphenyl)-2-hydroxy-1-mehylethylamino]1,2,3,4-tetrahydronaphthalene hydrochloride (Ia). a) 5,6-dimethoxy-2-[2-(4-benzyloxyphenyl)-2-oxo-1-methylethylamino]-1,2,3,4-tetrahydronaphthalene hydrochloride. A solution containing 20.0 g (0.082 mol.) of 5,6-dimethoxy-2-aminotetrahydronaphthalene (IV; R1 =H), 26.2 g (0.082 mol.) of 2-bromo-(4-benzyloxy)-1-propiophenone (V) and 9.1 g (0.09 mol.) of triethylamine in 82 ml of 95percent absolute ethanol is refluxed with stirring, under nitrogen atmosphere, for 6 hours. At the end of the reaction, the solution is evaporated under vacuum, the resulting residue is taken up into 500 ml of ethyl ether, under stirring. Patent; Chiesi Farmaceutici S.p.A.; US5096929; (1992); (A1) English View in Reaxys S.10 : SYNTHESIS EXAMPLE 10 SYNTHESIS EXAMPLE 10 1,2,3,4-Tetrahydro-5,8-dimethoxy-4-oxo-2-acetyl-2-hydroxy naphthalene, 14. To a stirred -24° C. solution of the ketone (8.9 g, 27.4 mmol), t-BuOH (23 ml), freshly distilled DMF (71 ml), and (EtO)3 P (5 ml, 27.4 mmol) maintained under N2 was added a -50° solution of t-BuOH (6.2 g, 55.2 mmol) in DMF 26 ml O2 was introduced into the system and after 15 min one equivalent of O2 (670 ml) was absorbed. The light orange mixture was then quenched by addition of HOAc (5 ml) affording a light yellow mixture. Two such runs were combined and concentrated at 60°/0.2 mm and the residue worked up as usual to afford a light yellow syrup. The majority of remaining volatiles were removed at room temp/10-3 mm over 24 hr. Trituration of the resulting semi-solid with Et2 O/EtOAc afforded in two crops 12.2 g(65percent) of light yellow solid, mp 143°-147° suitable for use in the next step. Recrystallization of this material from EtOAc gave in three crops 10.6 g (56percent) of crystalline hydroxy ketone, mp 148°-150°. The analytically pure material showed mp 151°-153° (lit. mp 152.5°-153.0°). Patent; The Ohio State Research Foundation; US4663445; (1987); (A1) English View in Reaxys 12 : EXAMPLE 12 The reaction mixture, warmed at room temperature, is poured in ice (450 g) and the crystalline precipitate is separated by filtration affording from ethylether 21.7 g of 4-(m-nitrobenzoyl)-butanoic acid m.p. 135°-137° C. A solution of this compound in acetic acid (500 ml) and acetic anhydride (30 ml) is hydrogenated at 65° C. in the presence of 10percent Palladium on charcoal (3 g). Patent; Boehringer Biochemia Robin, S.p.A.; US4692447; (1987); (A1) English View in Reaxys 13 : EXAMPLE 13 EXAMPLE 13 Rhodium trichloride trihydrate (0.50 g; 1.90 mmoles) was dissolved in water (2.5 ml) by heating at 70° C. for 1 hour. A solution of triphenylphosphine (0.975 g; 3.72 mmoles) and hydrazine di-hydrochloride (2.05 g; 19.53 mmoles) in acetone (12.5 ml) was added during 20 minutes, under an atmosphere of nitrogen. After stirring for 10 minutes, the mixture was refluxed for 3 hours. On cooling, a cream coloured product crystallized. After filtration, washing with a small amount of acetone and finally with di-ethyl ether, a yield of 1.05 g was obtained. Patent; Plurichemie Anstalt; US4743699; (1988); (A1) English View in Reaxys 15.IV : Preparation of STR42 (IV) Preparation of STR42 In 10 ml of DMF were dissolved 434 mg of STR43 and 219 mg of H--D--Lys(Z)--OBut. The solution was ice-cooled and 88 mg of HOBt and 134 mg of DCC were added. The mixture was stirred at room temperature for 15 hours.

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The resulting precipitate was filtered off and the filtrate was concentrated. To the concentrate was added CH3 CN, the insoluble matter was filtrated off again, and the filtrate was further concentrated and precipitated with Et2 O. The precipitate was collected by filtration and dried. Yield: 0.41 g (64.0percent). m.p.: 120°-123° C. [α]D 23 -30.3° (c=0.4, DMF). Rf5: 0.40. Elemental analysis, for C51 H67 N7 O11 S: Calcd. C, 62.11; H, 6.85; N, 9.94; S, 3.25. Found C, 62.31; H, 6.77; N, 9.38; S, 3.32. Patent; Takeda Chemical Industries, Ltd.; US4748154; (1988); (A1) English View in Reaxys 3 : EXAMPLE 3 EXAMPLE 3 A solution of 55 mg (0.16 mM) of ethyl ether of 15(R+S)-fluoro-11,15-dideoxyprostanglandin E1 is 3 ml of a mixture of tetrahydrofuran-methanol (1:2) is treated with 2 ml of a 1N aqueous sodium hydroxide and the resulting mixture is allowed to stand at room temperature for 18 hours. The reaction solution is acidified with a 1N hydrochloric acid to a pH of 2-3, the organic solvents are removed by evaporation in vacuum and the residue is extracted with ethylacetate (3*15 ml). The combined organic extracts are washed with water to a neutral reaction, with a saturated solution of sodium chloride (10 ml) and dried with sodium sulphate. The drying agent is filtered-off, the filtrate is evaporated. The residue is purified by chromatography in a column with 6 g of silica gel (100-160 μm) in a gradient system chloroform-ethylacetate to give 47 mg (92percent of the theoretical) of 15(R+S)-fluoro-11,15-dideoxyprostanglandin E1 comprising a colourless thick oil, Rf 0.75 (Silufol, one spot, benzene-dioxane-acetic acid, 40:10:1). Mass spectrum of diethyl ether produced by treatment of 1 mg of 15(R+S)-fluoro-11,15-dideoxyprostanglandin E1 with an ethereal solution of diazomethane is identical to the mass spectrum given in Example 2 hereinbefore. Patent; Institut Organicheskogo Sinteza An Latir SSSR; Institute Biorganicheskoi Khimii An SSSR; Moskovsky Meditsinsky Stomatologichesky Institut; US4665214; (1987); (A1) English View in Reaxys 40 : EXAMPLE 40 EXAMPLE 40 A solution of acetyl chloride (0.55 cc) in methylene chloride (5 cc) is added in the course of 10 minutes to a stirred solution of 4-[(6-amino-2-phenyl-4-quinolyl)oxyacetyl]morpholine (2.55 g), prepared according to Example 39, and triethylamine (1.2 cc) in methylene chloride (25 cc). The mixture is stirred for 1 hour at room temperature (approximately 20° C.) and the solvent evaporated off under reduced pressure. The residue is stirred for 10 minutes in an ethyl acetate/water (5:2 by volume) mixture, filtered off, dissolved in a toluene/acetic acid (50:50 by volume) mixture and precipitated with ethyl ether. Patent; Rhone-Poulenc Sante; US4728647; (1988); (A1) English View in Reaxys 1 : EXAMPLE 1 EXAMPLE 1 45 ml of methanol, 5 g of CoCl2.6H 2 O, 0.10 g of sodium sulphide and 0.37 g of sodium thiosulphate were introduced, under a CO head, into a 0.5-liter flask equipped with a stirrer, a funnel for liquids, a funnel for solids, a thermometer, a water cooler, and a pH-meter. Stirring was started (500 r.p.m.) and 2.25 g of an Mn/Fe alloy (Mn=80percent), ground up to over 10,000 mesh/cm2, were introduced. Absorption of CO began at once and continued for 3 hours. A total of 1.6 Nl of CO (85percent of the theoretical value) were absorbed. The catalyst suspension in methanol thus obtained was then utilized as follows: 210 ml of methanol were added to the catalyst methanol suspension thus obtained. Stirring was started, the temperature was brought to 25° C., and in 5 hours 20 g of chloromethylthiophene as well as 18 g of calcium oxide were added, keeping the mixture under a carbon monoxide head. On completion of the addition the mixture was maintained under stirring for another hour. 3100 ml of carbon monoxide were absorbed in the aggregate.

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270 ml of water were added in two portions to the mixture, and 310 ml of a water-methanol mixture containing 10percent of water useful for the succeeding tests were recovered by distillation. 25 ml of concentrated hydrochloric acid (37 g of HCl in 100 ml) were then added to the distillation residue, whereupon it was extracted with three 200-ml portions of ethyl ether. Patent; Montedison, S.p.A.; US4287352; (1981); (A1) English View in Reaxys 109 : EXAMPLE 109 EXAMPLE 109 To 9.5 g of ethyl[ [6,7-dichloro-2-(1-hydroxypropyl)benzo[b]thien-5-yl]oxy]acetate in 210 ml of ethanol is added 180 ml of 6 N sodium hydroxide solution and the mixture is stirred at 100° for 30 mins. The cooled mixture is concentrated in vacuo to give a white slurry which is diluted with 400 ml of ice water and 300 ml of ethyl ether. With stirring and efficient cooling, the mixture is acidified with 6 N hydrochloric acid. The acidic mixture is extracted with ethyl ether. The ether extracts are washed, dried over anhydrous magnesium sulfate and evaporated to dryness. Patent; Hoechst-Roussel Pharmaceuticals Inc.; US4436748; (1984); (A1) English View in Reaxys 20 : A. the oxime was formed by decomposition of the sodium salt in 2 N hydrochloric acid, from which it slowly crystallized. After recrystallization from benzenehexane, M.P. 160° C. A solution of 25 g. of the oxime in 100 ml. ethanol was added in portions to 5 g. platinum oxide suspended in 150 ml. 2 N hydrochloric acid and the mixture hydrogenated at atmospheric pressure for 2 days. The catalyst was filtered off, the filtrate evaporated and the residue taken up in 150 ml. ethanol. Treatment with 500 ml. ethyl ether precipitated DL-2-amino-3,3-dimethyl-4-hydroxybutyric acid lactone hydrochloride, 22 g., which was recrystallized from ethanol/ether, M.P. 208°-212° C. Patent; Pfizer Inc.; US4454328; (1984); (A1) English View in Reaxys 2 : N,N-Diethylethylenediamine amide of methylprednisolone 21-hemisuberate (HCl salt) EXAMPLE 2 N,N-Diethylethylenediamine amide of methylprednisolone 21-hemisuberate (HCl salt) A THF solution (150 ml) containing 7.6 g (14.3 mmol) of methylprednisolone 21-hemisuberate and 2.2 g (16 mmol) of triethylamine in a nitrogen flushed flask immersed in a dry ice-acetone bath was treated with 2.1 ml (16 mmol) of isobutylchloroformate. The flask was allowed to warm to room temperature while maintaining constant stirring. Within 15 minutes, a white precipitate had formed (triethylammonium chloride), after which 2.25 ml (16 mmol) of N,N-diethylethylenediamine was added. Product formation, monitored by thin layer chromatography (tlc) (silica gel; ethylacetate/methanol/NH4 OH, 20/4/1), appeared to reach 80percent of theory within an hour. The reaction mixture was concentrated under vacuum to an oil, taken up in 400 ml ethyl acetate, and extracted with 400 ml dilute HCl. The organic phase was reextracted with 100 ml dilute HCl and the combined aqueous phases were washed with 100 ml ethyl acetate. The acidic aqueous extract was then stirred with 400 ml ethyl acetate while adjusting the pH to 7.7 with 1N NaOH. A second organic extract of the aqueous phase (again adjusted to pH 7.7) was combined with the first, and the resulting solution was concentrated to an oil. The oil was taken up in THF and titrated with 24.7 ml of 1N HCl. Solvent was removed under vacuum and residual water was removed as an azeotrope with acetonitrile. Trituration of the semisolid product overnight with ethyl ether produced 7.7 g of a free flowing white solid. Patent; The Upjohn Company; US4456602; (1984); (A1) English View in Reaxys 3 : N,N-bis-(2-hydroxyethyl)-N'-methyl-2'-(ortho-chlorobenzoyl)-4'-chloroglycylanilide hydrochloride N,N-bis-(2-hydroxyethyl)-N'-methyl-2'-(ortho-chlorobenzoyl)-4'-chloroglycylanilide hydrochloride To a solution of 40.1 g (01. mol) of N-methyl-2'-(ortho-chlorobenzoyl)-4'-chloro-2-bromoacetanilide in 300 cc of acetone there are added 20 cc (0.2 mol) of diethanolamine, followed by agitation for 24 hours at room temperature. The reaction solvent is evaporated to dryness, the residue treated with a bicarbonate solution and extracted with ethyl acetate.

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The organic phase is washed three times with water and dried over sodium sulfate. After filtration and evaporation there are recovered 43 g of an oil which is treated with a saturated ethanolic solution of hydrochloric acid; it is precipitated with ethyl ether and iced. Patent; Pierre Fabre S.A.; US4370347; (1983); (A1) English View in Reaxys ...furan (longest) to methanol (shortest), the wavelength of maximum absorption of the solution of the reaction product being substantially longer than that of the solution of the dithiodianil compound per se in the same solvent: Solvent ... 1-methyl-2-pyrrolidinone ethyl ether propanediol 1,2-carbonate n-butanol Patent; The United States of America as represented by the Secretary of the Army; US4414414; (1983); (A1) English View in Reaxys 5.b : (b) (b) Hydrogenation of S-acetoacetyl thiocarnitine hydrochloride To a solution of acetoacetyl thiocarnitine hydrochloride (1.25 grams; 0.0044 moles) in 26 ml of glacial acetic acid and 8.8 ml of absolute ethanol, cooled with an ice bath, 660 mg (0.017 moles) of NaBH4 were added portionwise under stirring. After 2 hours, the reaction mixture was filtered and upon addition of ethyl ether a precipitate was obtained from the filtrate. Patent; Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.; US4483869; (1984); (A1) English View in Reaxys 10.d : Preparation of 2-(β-diethylaminoethyl)amino-6-(β-diethylaminoethyl)aminonitrobenzene dihydrochloride Second step Preparation of 2-(β-diethylaminoethyl)amino-6-(β-diethylaminoethyl)aminonitrobenzene dihydrochloride 300 mg of palladium at a concentration of 10percent on calcium carbonate are added to 0.015 mole (5.8 g) of 4chloro-2-(β-diethylaminoethyl)amino-6-(β-diethylaminoethyl)aminonitrobenzene in 11.1 ml of triethylamine, after which 2.86 ml of acetic acid and 2.1 ml of formic acid are added dropwise. After the end of the additions, the materials are heated under reflux for 3 hours 30 minutes. The reaction mixture is diluted with 10 ml of water. The catalyst is removed by hot filtration. The filtrate is evaporated to dryness under vacuum. The inorganic salts are precipitated by adding acetone and are removed by filtration. After evaporation of the acetone, an oil is obtained and this, after treatment with a solution of hydrochloric acid in absolute ethanol, leads to the expected product which is isolated by evaporating off the alcohol and precipitating with ethyl ether. Analysis of the product obtained gives the following results: Patent; L'Oreal; US4797129; (1989); (A1) English View in Reaxys 3 : Methyl 3-O-(2-chlorobenzyl)-2-O-(2-hydroxyethyl)-5-deoxy-5-C-methyl-alpha, beta-D-xylofuranoside EXAMPLE 3 Methyl 3-O-(2-chlorobenzyl)-2-O-(2-hydroxyethyl)-5-deoxy-5-C-methyl-alpha, beta-D-xylofuranoside In this example 0.53 g of lithium aluminum hydride was slowly added to a solution containing 5.2 g of methyl 3-O-(2chlorobenzyl)-2-O-(ethoxycarbonylmethyl)-5-deoxy-5-C-methyl-alpha, beta-D-xylofuranoside in 100 ml of tetrahydrofuran at about 0° C. The mixture was then allowed to raise to room temperature and stirred at this temperature for 2 hours. Five ml of ethyl acetate was then added followed by the successive addition of 1 ml of water, 1 ml of 15 wt percent aqueous sodium hydroxide and 3 ml of water. The mixture was then filtered and the filter cake washed with ethyl ether. The filtrate and ether washings were combined and evaporated under reduced pressure.

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The resulting residue was mixed with ethyl ether and then washed with water and evaporated down to 4.8 g of a mixture of the alpha and beta glycosides of the title compound as a colorless liquid. Patent; Chevron Research Company; US4534785; (1985); (A1) English View in Reaxys 5.a : 1-[5-Methyl-2-(phenylmethyl)phenyl]piperazine mono-, dihydrochloride (a) 39.52 g of 2-benzyl-4-methylaniline, 36.43 g of bis-(2-chloroethylamine) in 130 ml of n-butoxyethanol and 28.5 g of anhydrous potassium carbonate are reated according to the method described in Ex. 3 (b). By evaporation of the organic phase, an oily residue (58 g) is obtained which is then dissolved in dry methylene chloride and under cooling in a water-ice bath a stream of hydrochloric acid gas is bubbled into; the formed hydrochloride precipitates by adding dry ethyl ether (50 ml), and after one night in the refrigerator, it is filtered, washed with ethyl ether and dried. 34.0 g (55percent) of the monohydrochloride as white solid of m.p. 202°-204° C. and chromatographically pure are obtained. Patent; Ferrer Internacional S.A.; US4859675; (1989); (A1) English View in Reaxys 5.b : (b) The precipitate was taken up with isopropanol, brought to pH 2-3 with 1N HCl in isopropanol, then precipitated again with ethyl ether. The semisolid, very hygroscopic pure product was thus obtained. Patent; Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.; US4483869; (1984); (A1) English View in Reaxys 13 : EXAMPLE 13 EXAMPLE 13 In a 1 liter reaction flask and to 5.360 g. of 7-amino-3-desacetoxy-cephalosporanic acid (7-ADCA) are added pyridine (500 ml) and allylisocyanate (3.3 ml). The mixture is heated to 50° C for 5 hrs. The solvent is removed by evaporation under reduced pressure, the residue is taken up in acetic acid (20 ml) and ethyl acetate (250 ml) from which 7-(3-allyl-ureido)-3-desacetoxy-cephalosporanic acid (6.480 g) precipitates by addition of ethyl ether (100 ml). Rf = 0.28 (+- 0.10) in the system methylisobutylketone/methanol/formic acid 60/6/2; detection with bromcresol green and KMnO4; nmr: 2.00 s (3H), 3.26 d (1H) (J 17 c./sec.), 3.65 d (1H) (J 17 c./sec.), 3.5-3.9 m (2H), 5.02 d (1H) (J 4.6 c./sec.), 5.0-5.4 m (2H), 5.6 d (1H) (J 4.6 c./sec.), 5.6-5.9 m (1H). Patent; Recherche et Industrie Therapeutiques (R.I.T.); US3994886; (1976); (A1) English View in Reaxys 10 : 2-(3,4-Dihydroxyanilino)-1,3,4,6,7,11β-hexahydro-2H-benzo[α]-quinolizine monooxalate (TR 3358). Example 10 2-(3,4-Dihydroxyanilino)-1,3,4,6,7,11β-hexahydro-2H-benzo[α]-quinolizine monooxalate (TR 3358). A solution of 1,3,4,6,7,11β-hexahydro-2H-benzo[α]quinolizine-2-one (10.0 g; 0.05 mole), 3,4-bisbenzyloxyaniline (15.3 g; 0.05 mole), and a catalytic amount of p-toluenesulfonic acid in 300 ml of benzene was heated at reflux (24 hours) using a Dean-Stark trap to remove water (0.9 ml). The solvent was evaporated in vacuo to give the imine as a dark oil. The imine was dissolved in MeOH (200 ml) and stirred in an ice-bath as NaBH4 (10.0 g) was added portionwise. After 1 hour the ice-bath was removed, the reaction mixture heated at reflux for 1 hour, then cooled. The solvent was evaporated in vacuo, and the resulting residue was stirred with a mixture of water (200 ml) and Et2 O (200 ml). The resulting two layers were separated, and the aqueous layer extracted with Et2 O (2*100 ml). Patent; Miles Laboratories, Inc.; US3995041; (1976); (A1) English View in Reaxys 12 : 2-(p-Tolyl)-3-[3-(dimethylamino)propionyl] benzofuran. EXAMPLE 12 2-(p-Tolyl)-3-[3-(dimethylamino)propionyl] benzofuran. To a solution of 20 grams of 2-(p-tolyl)-3-acetylbenzofuran in 80 milliliters of isopropanol was added 3.4 grams of paraformaldehyde, 9.1 grams of dimethylamine hydrochloride, and 8 milliliters of a saturated solution of hydrogen chloride in ethanol, and the mixture was heated under gentle reflux for a period of 8 hours.

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The solvent was evaporated under vacuum and the residue was taken up in water and ethyl ether was then added thereto to dissolve and extract the water-insoluble solids from the solution. The ether extract was then separated from the aqueous layer and the aqueous layer was made alkaline by the addition thereto of a 5percent aqueous solution of sodium hydroxide. The precipitated oily base was then extracted with ethyl ether from the aqueous solution, washed with several portions of water, and dried over anhydrous sodium sulfate. A solution of hydrogen chloride in ethanol was then added to the dried ether extract and the crystals of the hydrochloride of the compound named in the heading of this example which were thus precipitated were separated by suction filtration and recrystallized by dissolving them in ethanol and precipitating them by the addition of ethyl ether to the ethanol solution. Patent; Kali-Chemie Aktiengesellschaft; US4009184; (1977); (A1) English View in Reaxys 13 : EXAMPLE 13 EXAMPLE 13 Into a stainless steel autoclave, 800 cc of C10 F21 --C2 H4 --I (67.4 g; 0.1 mole), methylamine (12.4 g; 0.4 mole) dissolved in pyridine (100 cc) were introduced. The autoclave was cooled in a liquid nitrogen bath, and the inert gases eliminated by suction under vacuum. The autoclave was allowed to warm up to room temperature, then the stirring device was started, the apparatus brought to a temperature of 80° within 30 minutes, and kept at this temperature during 3 hours 30 minutes. After cooling, a liquid consisting of two phases was recovered; a light phase (A) and a dense phase (B). Phase (A) was stirred with 50 cc of a 10 percent aqueous soluton of NaOH, and this brought about the decantation of a phase (C) which was added to phase (B). Phases (B) and (C) were united, and then extracted with ethyl ether (4 times 100 cc). The etheral extracts were dried over anhydrous sodium sulfate and then distilled. Besides ethyl ether, four fractions were obtained: Patent; Produits Chimiques Ugine Kuhlmann; US4059629; (1977); (A1) English View in Reaxys 31 : EXAMPLE 31 EXAMPLE 31 Into a stainless steel autoclave were introduced 800 cc of C2 F5 C2 H4 --I (54.8 g; 0.2 mole), methylamine (24.8 g; 0.8 mole), pyridine (200 cc). The autoclave was cooled in a liquid nitrogen bath, and the inert gasses eliminated by suction under vacuum. The autoclave was allowed to warm up to room temperature, the stirring device started, and the autoclave brought to a temperature of 80° C within 30 minutes. This temperature was maintained during 3 hours 30 minutes. After cooling, a liquid was recovered and stirred with 100 cc of a 10 percent-by-weight aqueous solution of NaOH. The resulting solution was extracted withethyl ether (6 times 100 cc). After drying the etheral extracts over anhydrous sodium sulfate, they were distilled, and three fractions, in addition to the ethyl ether, were obtained: Patent; Produits Chimiques Ugine Kuhlmann; US4059629; (1977); (A1) English View in Reaxys 5 : EXAMPLE 5 EXAMPLE 5 A mixture of 30 grams of hydrated sodium antimonate in 175 ml. of propylene glycol is stirred at 140°-160° C. for four hours. The mixture is filtered while hot, and the filtrate is cooled. Diethyl ether is added to slowly precipitate the desired triester which is washed with acetone and analyzed. The solid sodium salt of the triester obtained in this manner has a softening point of about 148°-150° C. The chemical analysis of the product indicates the desired triester is solvated with two moles of water. Patent; The Harshaw Chemical Company; US4169104; (1979); (A1) English View in Reaxys The method of Example 2 was repeated with comparable results employing each of the following co-solvents: ethanol n-propanol n-butanol

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ethyl ether isopropyl ether dimethoxy ethane 2-methoxy ethanol 2-ethoxy ethanol Patent; Pfizer Inc.; US4082717; (1978); (A1) English View in Reaxys Compound 2 Compound 2 Using method B, precursor 3 (1.0 g, 1.0 mmol) dissolved in CH2 Cl2 (25 ml) was added dropwise (15 min) via an addition funnel to an ice bath cooled, vigorously stirred solution of BBR3 (2 ml, 21 mmol) in CH2 Cl2 solution (25 ml). The ice bath was allowed to warm up to room temperature as the reaction slurry was stirred overnight. Cautious addition of H2 O (20 ml) was followed by an additional 2 hrs stirring to hydrolyze all boron compounds. Crude product was collected by filtration and washed well with H2 O. The pink-tan solid was dissolved in MeOH and precipitated by the addition of Et2 O. Drying at 115° (5-10 microns) overnight gave the demethylated product, compound 2 (0.88 mmol, 88percent) as hygroscopic powder which analyzed with two waters of crystallization: m.p. 230°-40° dec., H-nmr (D6 MSO--D2 O) showed complete absence of --OCH3 (δ.approx/equal.4.0 moiety); purity also established by pH-titration giving pKa1 5.59 (4 protons) and pKa2 11.8 (4 protons) for the 4 constituent catechol groups. Anal. Calcd. for C38 H36 N8 O20 2 H2 O: c, 47.50; H, 4.20; N, 11.66. Found: C, 47.52; H, 4.23; N, 9.74. Patent; The United States of America as represented by the United States Department of Energy; US4181654; (1980); (A1) English View in Reaxys 8 : EXAMPLE 8 EXAMPLE 8 To 1.20 g (1.5 milli mol) of 7-(Nα -t-butyloxycarbonyl-Nε -carbobenzoxy-L-lysyl-Nε -carbobenzoxy-L-lysyl)-amino-4methylcoumarin were added 10 ml of acetic acid and then 860 mg (4.5 milli mol) of toluenesulfonic acid monohydrate and the resulting mixture was stirred at 20° C. for 2 hours. Acetic acid was then removed and a solid substance yielded upon addition of 100 ml of ethyl ether was recovered by filtration and washed with 50 ml of ethyl ether. Patent; Ajinomoto Company, Incorporated; US4237047; (1980); (A1) English View in Reaxys 10 : Synthesis of intermediate F: Synthesis of intermediate F: 0.7 g (3.34 mmoles) intermediate E 0.389 ml (3.67 mmoles) terbutanol 0.329 ml (3.67 mmoles) perchloric acid 14 ml nitromethane Terbutanol and perchloric acid are added in order to the solution of intermediate E in nitromethane. After 20 hours, the product precipitates by the addition of ethyl ether, and is isolated by filtration. The product is purified by dissolution in acetone and precipitation with ethyl ether. It is filtered and washed several times with ethyl ether. 600 mg of product are thus obtained (yield = 49percent). Patent; Enichem S.p.A.; EP1156041; (2001); (A2) English View in Reaxys 22 : Example 22 Example 22 A 227 mg portion of the compound obtained in Example 21 (1) was dissolved in 4 ml of dimethylformamide, the resulting solution was mixed with 50 μl of methyl iodide, and the mixture was stirred overnight at room temperature. After evaporation of the solvent under a reduced pressure, the thus obtained solid substance was dissolved in 5 ml of methylene chloride, mixed with 0.2 g of anisole and 5 ml of trifluoroacetic acid, and the mixture was stirred for 1 hour at room temperature. Next, methylene chloride was evaporated under a reduced pressure, and the reaction solution was cooled to 10°C, mixed with 8 ml of trifluoroacetic acid and 3 ml of water, followed by stirring for 1 hour.

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Water and trifluoroacetic acid were evaporated and the resulting residue was solidified by adding ethyl ether, collected by filtration and then dried to obtain 165 mg of crude product. This was purified by high performance liquid chromatography to obtain 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-[(Z)-2-(2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4-carboxylate (isomers 22A and 22B). Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys 2 : Physicochemical properties (2) In an atmosphere of argon, 261 mg of the compound obtained in the above step (1) was dissolved in 5 ml of methylene chloride and 0.2 ml of anisole, the resulting solution was cooled at 10°C and mixed with 5 ml of trifluoroacetic acid. Then, the mixture was stirred for 60 minutes at 10°C to room temperature. Methylene chloride and trifluoroacetic acid were evaporated under a reduced pressure, and the thus obtained residue was again cooled to 10°C and mixed with 5 ml of trifluoroacetic acid and 3 ml of water. After 1 hour of stirring, the solvent was evaporated and the resulting residue was mixed with ethyl ether to obtain crude product. Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys 2 : Physicochemical properties (2) A 260 mg portion of the compound obtained in the above step (1) was dissolved in 6 ml of methylene chloride and 4 ml of anisole, the resulting solution cooled in an ice bath was mixed with 10 ml of trifluoroacetic acid and the mixture was stirred for 1 hour at 0°C to room temperature. After evaporating the solvent, the resulting residue was mixed with ethyl ether and the thus formed precipitate was collected by filtration. Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys 9 : EXAMPLE 9 EXAMPLE 9 To 1.02 g (1 milli mol) of 7-(Nα -t-butyloxycarbonyl-γ-benzyl-L-glutamyl-Nε -carbobenzoxy-L-lysyl-Nε -carbobenzoxyL-lysyl)-amino-4-methylcoumarin were added 5 ml of acetic acid and 573 mg (3 milli mol) of toluene sulfonic acid monohydrate, and the resulting mixture was stirred at 20° C. for 2 hours. Acetic acid was then distilled off and a solid substance that yielded upon addition of 100 ml of ethyl ether was recovered by filtration. This solid substance was dissolved in 5 ml of DMF, neutralized with 0.14 ml of triethylamine and added with 435 mg (1.2 milli mol) of t-butyloxycarbonyl-L-phenylalanine-N-hydroxysuccinimide ester and the resulting mixture was stirred at 20° C. for 20 hours. Patent; Ajinomoto Company, Incorporated; US4237047; (1980); (A1) English View in Reaxys b : b) 234 g of the product obtained under a) was mixed with 468 g water, 234 g isopropanol and 169 g hydrogen bromide (48percent wt) and heated under nitrogen to 70 °C. 58 g propylene oxide was added in the course of a few minutes, causing an increase in the pressure from 1.64 bar to 2.03 bar. After 2 hours the pressure had become constant at 1.85 bar. The crude product was worked up by flashing off the solvent followed by 2x desalting in isopropanol. Nonpolar organics were removed by dissolving the sample in water, raising the pH to 14 and extracting the water layer twice with diethylether. After readjustment of the pH with hydrogen bromide the solution was subjected to evaporation to dryness. A polar organic impurity, propylene glycol, was removed by slurrying with diethylether. The final amount of propylene glycol in the otherwise pure product (yield 145 g) amounted to less than 3 percentmole. Patent; SHELL INTERNATIONALE RESEARCH MAATSCHAPPIJ B.V.; EP1017925; (2002); (B1) English View in Reaxys 1.b : b)

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57.0 g (0.75 moles) of Peg 1Me and, in small portions, 3.0 g (77 mmoles) of metallic potassium previously washed with n-hexane were put into a two-neck, 250 ml flask provided with a bubble condenser and a mechanical stirrer, under a nitrogen blanket. When the addition was over, and after completion of the formation of the alcoholate for 1 hour, the solution was transferred into an autoclave of 250 ml volume provided with a magnetic stirre and, after evacuation, acetylene was introduced up to 12 atmosphere pressure. The mixture was stirred and heated up to 100°C for 8 hours and then it was cooled down to room temperature. The loading operation was repeated 9 times. The product, recovered from the autoclave by means of ethyl ether, after removal of ether under atmospheric pressure, was distilled under reduced pressure, so collecting a single fraction with boiling point 20-22°C/ 20 mm. Patent; ISTITUTO SIEROVACCINOGENO ITALIANO I.S.I. S.p.A.; EP509968; (1992); (A1) English View in Reaxys 11 : EXAMPLE 11 EXAMPLE 11 A mixture of 14 g of the diastereomeric mixture of 2-chloro-9-(2,3-epoxy-propyl)-9,10-dihydro-9,10-ethanoanthracene in 50 ml of benzene and of 50 ml of a 33percent solution of methylamine in absolute ethanol is stirred for 84 hours at room temperature in a closed vessel. The reaction mixture is evaporated at about 11 mm Hg and the residue is dissolved in 50 ml of ethanol. The solution is treated with 4 ml of a 10percent solution of hydrogen chloride in ethanol and diluted with diethyl ether. The hydrochloride of the diasteromeric mixture of the 2-chloro-9-(2-hydroxy-3-methylamino-propyl)-9,10-dihydro-9,10-ethano-anthracene, which melts at 218°-220° after being recrystallized twice from a mixture of ethanol and diethyl ether, is thus obtained. Patent; Ciba-Geigy Corporation; US4017542; (1977); (A1) English View in Reaxys 17 : EXAMPLE 17 EXAMPLE 17 To a solution of 3 g of 1-(p-chlorophenyl)-3-ethyl-4-thio-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine and 100 ml of methanol was added 40 ml of 5 percent sodium hydroxide solution and the mixture was refluxed for 3 hours. Then, the reaction mixture was concentrated to give a residue, to which was added water. A crude product precipitated was collected by filtration and washed and dried. Recrystallization of this product from ethyl ether yielded 2.6 g of 1-(p-chlorophenyl)-3-ethyl-4-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine, melting at 100° - 101° C. Patent; Hisamitsu Pharmaceutical Co., Inc.; US4009166; (1977); (A1) English View in Reaxys 2.A : Example 2 A. Reaction: Under N2, sodium metal (0.6 mol, 13.8 g) was dissolved in a stirred solution of 2,6-di-tert.butyl phenol (1 mol, 206 g) in 500 ml ethanol. Then the dibromide (0.25 mol, 66 g) was added in about 45 min, while keeping the solution at 0 °C. The resulting mixture was stirred for 2 h at 0 °C, subsequently 16 h at 25 °C and further 2 h at 60 °C. The mixture was then cooled to 25 °C and acidified with a 33percent aqueous HCl solution while the colour of the mixture turned from green into yellow. To the resulting reaction mixture were added 300 ml of diethylether and the mixture was 5 times extracted with 200 ml water. The ethereal solution was then dried over magnesium sulphate. Further, the solvent and the excess of 2,6-di-tert.-butylphenol were distilled off. The obtained residue was recrystallized from methanol, yielding 59 g of product (68percent of the theoretical yield) having a melting point of 152 °C and Patent; SHELL INTERNATIONALE RESEARCH, MAATSCHAPPIJ B.V.; EP546639; (1993); (A1) English View in Reaxys 8 : Preparation of the trifluoroacetate salts of teicoplanin compound amides 18-25. EXAMPLE 8: Preparation of the trifluoroacetate salts of teicoplanin compound amides 18-25. A teicoplanin compound amide (amides 18 - 25) is dissolved (1 g in 300 ml) in a mixture water:acetonitrile, 8:2 (v/v). The resulting solution is brought to pH 8.5 with 0.1 N NaOH and extracted (v/v) with n-butanol.

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The organic layer is separated, washed with water (v/v) and concentrated to a small volume. On adding ether, the solid which separates is collected, washed with ether and dried overnight in vacuo at 35°C, yielding the corresponding free base which is re-dissolved in TFA (1 g in 10 ml) and precipitated with ethyl ether (100-200 ml). After collecting the solid by filtration, washing with ether and drying in vacuo 24 h at room temperature, the title compounds are obtained (18 - 24, di-trifluoroacetates and 25 trifluoroacetate). Patent; GRUPPO LEPETIT S.p.A.; EP218099; (1991); (B1) English View in Reaxys P.1 : Preparation Example 1: The ethereal solution was added to a mixture of 200m of ethyl ether, 150m of water and 50m of 30percent aqueous ammonia solution with stirring. Patent; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; EP525360; (1993); (A2) English View in Reaxys a : a) a) preparation of the N-tert-butoxycarbonyl protected teicoplanin starting material (N-t-BOC-ST) A mixture of 4 mmol of the selected teicoplanin starting material 2 ml (14.5 mmol) of TEA and 2 g (~7 mmol) of tertbutyl 2,4,5-trichlorophenylcarbonate in 100 ml of DMF is stirred 24 h at room temperature. On adding ether (900 ml) a solid separates which is collected and re-dissolved in a mixture (1 l) water:methanol 7:3. The resulting solution is brought to pH 3.5 with 1 N HCl, then extracted with ether (500 ml). The aqueous layer is extracted again with n-Butanol (1 l). The butanolic layer is washed with water (2 * 500 ml) and concentrated to a small volume under vacuum at 35°C. By adding ethyl ether a solid is precipitated which is collected, washed with ether and dried in vacuo at 40°C overnight, yielding (the yields are always higher than 90percent) the N-t-BOC protected teicoplanin starting material pure enough (HPLC titre > 90percent, method c) for the next step. Patent; GRUPPO LEPETIT S.p.A.; EP218099; (1991); (B1) English View in Reaxys b : b) b) preparation of the N-CBzO derivative of the teicoplanin amide compound The condensation of the above obtained N-benzoyloxycarbonyl starting material with the selected amine is carried out in DMF (HPLC, method c) in the presence of DPPA under the same reaction conditions as described in example 1. The N-CBzO-teicoplanin amide compound is obtained as a solid which precipitates from the reaction mixture by adding ethyl ether. Patent; GRUPPO LEPETIT S.p.A.; EP218099; (1991); (B1) English View in Reaxys c : c) c) preparation of the teicoplanin amide derivative of the title A solution of 1 mmol of N-t-BOC-teicoplanin amide in 40 ml of 100percent trifluoroacetic acid (TFA) is stirred 10-20 min at 5°C, afterwards the solvent is evaporated under vacuum at 25°C. The oily residue is triturated with ether, then collected and re-dissolved in 150 ml of methanol. Silanized silica gel (0.063-0.2 mm 5g Merck) is added and the solvent is evaporated under vacuum at 40°C. The residue is put at the top of a column containing the same silanized silica gel (150 g) prepared in the mixture water:acetonitrile 95:5 (v/v). Column chromatography is carried out substantially according to the procedure described in example 4 c. More particularly, the column is developed with a linear gradient elution from 5percent CH3CN in 0.001 N HCl to 30percent CH3CN in H2O in the case of compound 9, with a linear gradient elution from 10percent CH3CN in 0.001 N HCl to 40percent CH3CN in H2O in the case of compound 14 and with a linear gradient from 20percent CH3CN in 0.001 N HCl to 55percent CH3CN in water in the case of compound 22. The flow rate is 120 ml/h and the time is 15 h. Fractions of 12 ml are collected, monitored by HPLC and worked up substantially as already described in example 4c.

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Fractions containing the pure compounds of the title are pooled and to the resulting solution n-butanol (v/v) and 1 N HCl (2 ml) are added. After concentration to a small volume under vacuum at 40°C the title compound is obtained (as the corresponding dihydrochloride, except for compound no. 25 which is recovered as mono-hydrochloride) by precipitating with ethyl ether from the butanolic phase, washing and drying overnight in vacuo at 40°C. Patent; GRUPPO LEPETIT S.p.A.; EP218099; (1991); (B1) English View in Reaxys 12 : [2-(4,4-Dimethyl-4,5-dihydro-oxazol-2-yl)-5-methoxy-phenyl]-phenyl-methanone In another flask a suspension of ZnCl2 (4.48 g, 33 mmoles) in dry ethyl ether (60 ml) was prepared and dropwise added with the solution of the lithium derivative at 0° C. and, after 1 hour, with benzoyl chloride (3.24 g, 23.02 mmoles). The mixture was left at room temperature for 3 hours, then added with bis(triphenylphosphine)palladium chloride (280 mg) and, after 3 days, poured into water/ice and extracted with ethyl acetate. Patent; Zambon Group S.p.A.; US6329370; (2001); (B1) English View in Reaxys 12 : N-FMOC-L-Leucinyl-HMPB-MBHA Resin The precipitate was dried and dissolved in 650 μL of a solution of 1/1/0.056/0.040 TFA/CH2Cl2/thiophenol/Me2S and the solution was allowed to stand for 1 hour. Precipitation from Et2O gave crude compound 24 which was purified by HPLC (C18, 15-45percent CH3CN/H2O, 0.1percent TFA). Fractions containing pure product were lyophilized to give 8.6 mg of compound 24 as a white solid. Patent; La Jolla Pharmaceutical Company; US6207160; (2001); (B1) English View in Reaxys 2.b : b) 2.38 g of 5-(2-hydroxyphenyl)-3-phenyl-1,2,4-oxadiazole are dissolved in 100 ml of anhydrous dioxane and stirred with 0.3 g of 80percent sodium hydride suspension in oil for 15 minutes at 25-30° C. To this solution is added 60 ml of anhydrous dioxane, the resulting mixture is combined with 2.88 g of 2-(N,N-dimethylamino)ethylchloride hydrochloride and 0.6 g of 80percent sodium hydride suspension in oil. This solution is also stirred for 15 minutes at 25-30° C. The combined solutions are refluxed for 8 hours, left to stand overnight and evaporated down in vacuo. The residue is mixed with water and 20 ml of 1N sodium hydroxide solution and extracted with ethyl acetate. The organic phase is dried over sodium sulphate, the solvent evaporated in vacuo and the residue chromatographed on silica gel with ethyl acetate/isopropanol (70:30, mixed with 2.5percent of a 25percent ammonia solution). The base thus obtained is dissolved in anhydrous ethanol, acidified with ethereal HCl and precipitated with diethyl ether. The residue is recrystallized from anhydrous ethanol and diethylether. Yield: 2.2 g (64percent of theory). m.p.: 186-187° C. Patent; Boehringer Ingelheim KG; US6277872; (2001); (B1) English View in Reaxys 3.c : c) 4.46 g of 2-(N,N-dimethylamino)ethyloxy-benzoic acid amidoxime and 5.44 g of methyl benzoate are dissolved in 150 ml of absolute ethanol, mixed with 2.3 g of sodium and heated in the microwave twice for 11 minutes (with a 5 minute break) at 300 W. The reaction mixture is concentrated by evaporation in vacuo, the residue is mixed with water and extracted with ethyl acetate. The organic phase is dried over sodium sulphate, the solvent is evaporated in vacuo and the residue is chromatographed on silica gel with ethyl acetate/isopropanol (70:30, mixed with 2.5percent of a 25percent ammonia solution). The base thus obtained is dissolved in anhydrous ethanol, acidified with ethereal HCl and precipitated with diethyl ether. The residue is recrystallized from anhydrous ethanol and diethylether. Yield: 2.5 g (36percent of theory). m.p.: 174-175° C. Patent; Boehringer Ingelheim KG; US6277872; (2001); (B1) English View in Reaxys

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40.e : 40e. To a solution of 594 mg of tert-butyl (S)-[[1-(2-[[(1-amino-6-isoquinolinyl)carbonyl]amino]-1-oxopropyl)piperidin-4yl]oxy]acetic acid in 8 mL of dioxane was added 3 mL 36percent hydrochloric acid and stirred at room temperature for two hours. The solution was concentrated and trituration of the residue with diethyl ether yielded 560 mg of the title compound. HPLC Supelcosil LC-18-DB column using a gradient elution system of 20percent A/80percent B to 20percent A/ 20percent B/60percent C over 40 min at a flow of 0.25 ml/min (A: 0.5M phosphate buffer pH 2.1, B: water, C acetonitril/water 3/2 v/v). Rt=22.4 min. Patent; Akzo Nobel N.V.; US6194409; (2001); (B1) English View in Reaxys 5.a : a) a) 3-(3-Cyclopentylmethyl-4-methoxyphenyl) pyridine hydrochloride The compound of Example 4a) (485 mg) was hydrogenated over the weekend in EtOH (25 ml) in the presence of 5percent Pd/C (50 mg). The reaction mixture was filtered through Celite and concentrated in vacuo to give the title compound free base (464 mg) as a colourless oil. The free base was dissolved in warm ethanolic HCl, precipitated with Et2O, decanted and dried in vacuo to yield the title compound (485 mg) as a white solid. (Found: C, 70.98; H, 7.31; N, 4,62. C18H21NO. HCl requires C, 71.16; H, 7.30; N, 4.61percent). Patent; Celltech Therapeutics Limited; US6245774; (2001); (B1) English View in Reaxys 5.b : b) 1.72 g of 5-[2-(2-bromoethyl)oxy-phenyl]-3-phenyl-1,2,4-oxadiazole are dissolved in 50 ml of anhydrous dioxane and mixed with 2 g of N-methylpiperazine. The solution is refluxed for one hour and then concentrated by evaporation in vacuo. The residue is chromatographed on silica gel with dichloromethane/methanol (90/10). The base thus obtained is dissolved in anhydrous ethanol, acidified with ethereal HCl and precipitated with diethyl ether. The residue is recrystallized from anhydrous ethanol and diethylether. Yield: 1.7 g (78percent of theory). m.p.: 251-253° C. Patent; Boehringer Ingelheim KG; US6277872; (2001); (B1) English View in Reaxys 6.A : Step A Step A To a solution of carbapenem 3 (0.0349 g, 0.060 mmoles) in sieve-dried CH2Cl2 (1 mL) was added 1-methyl imidazole (0.011 mL, 0.13 mmoles) at -20° C. followed by Tf2O (0.011 mL, 0.066 mmoles). The reaction was stirred at -20° C. for 1.5 h and then partitioned between ice/H2O and CH2Cl2. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give a pale yellow oil (0.0562 g). The oil was redissolved in CH2Cl2 (0.5 mL) and the product was precipitated out with Et2O as an oil. The mixture was centrifuged and the supernatent discarded. The oil was washed with Et2O and dried in vacuo (0.0462 g, quantitative yield). 1H

NMR (CDCl3) δ: 1.27 (d, 3H), 1.42 (d, 3H), 3.36-3.47 (m, 2H), 3.96 (s, 3H), 4.17 (dd, 1H), 4.56-4.60 (m, 2H),

4.71-4.90 (m, 2H), 4.99 (d, 1H), 5.06-5.16 (m, 1H), 5.21-5.49 (m, 4H), 5.62 (s, 2H), 5.79-6.05 (m, 3H), 6.89 (d, 1H), 7.23-7.27 (m, 2H), 7.35 (t, 1H), 7.44 (d, 1H), 7.49-7.60 (m, 2H), 8.57 (dd, 1H), 9.31 (s, 1H). Patent; Merck and Co., Inc.; US6277843; (2001); (B1) English View in Reaxys 61 : Example 61 Example 61 A 1 oz. Fisher-porter bottle was charged with 0.14 g (0.34 mmoles) of 70112, 0.97 gms (6.8 mmoles) of methyl iodide, and 7 ml of anhydrous acetonitrile. Heat to 50° C. for 4 days.

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The quat. Salt Compound No. 192 was isolated by concentrating to 1 cc acetonitrile and then precipitating with diethyl ether. Patent; G. D. Searle and Co.; US6268392; (2001); (B1) English View in Reaxys Patent; G.D. Searle and Co.; US6387924; (2002); (B2) English View in Reaxys 8.C : C. A catalytic amount of dl-camphorsulfonic acid is added to a solution of ethyl 2-amino-1-(2,4,6-trimethylphenyl)pyrrolo[1,2-a]pyrazine-2-carboxyl-ate (0.40 g) in 2,2-dimethoxypropane (10 mL) and the mixture is heated to reflux for 30 minutes. Over this period, about 5 mL of volatiles are removed by slow distillation; the remaining material is further refluxed for another 15 minutes. The mixture is cooled to room temperature and concentrated in vacuo. The residue is dissolved in THF (6 mL), cooled to 0° C. to the cooled solution is added dropwise a 1.0 M solution of sodium bis(trimethylsilyl)amide in THF (2.5 mL). After the addition, the deep red solution is allowed to warm to room temperature and stirred for 2 additional hours before being diluted with aqueous ammonium chloride and extracted with three portions of dichloromethane. The combined organic extracts are dried (Na2SO4), filtered, concentrated in vacuo, and triturated with hot ethyl acetate. The product, which precipitates upon cooling and dilution with ethyl ether, is filtered and air-dried (220 mg). Patent; Neurogen Corporation; US6194574; (2001); (B1) English View in Reaxys [Au(d3pype)2]Cl [Au(d3pype)2]Cl d3pype (0.4 g, 0.99 mmol) was dissolved in DMSO (20 mL) under an atomosphere of argon. Bu4NAuCl2 (0.236 g, 0.46 mmol was added as a solid and the resulting yellow solution was stirred overnight. In an attempt to precipitate the product Et2O (10 mL) was added but no precipitate formed after several hours refrigeration, but instead the solution settled into two layers. To this mixture toluene (30 mL) was added and the clear pale yellow solution cooled to -20° C. for 24 hrs during which time the desired compound precipitated as a light yellow solid and was collected by filtration. Patent; Griffith University; US6218378; (2001); (B1) English View in Reaxys 61 : Example 61 Example 61 A 1 oz. Fisher-porter bottle was charged with 0.14 g (0.34 mmoles) of 70112, 0.97 gms (6.8 mmoles) of methyl iodide, and 7 ml of anhydrous acetonitrile. Heat to 50° C. for 4 days. The quat. Salt Compound No. 192 was isolated by concentrating to 1 cc acetonitrile and then precipitating with diethyl ether. Patent; G.D. Searle &amp; Co.; US2004/14803; (2004); (A1) English View in Reaxys Example 1435 Example 1435 Preparation of: 1,4-Diazabicyclo(2.2.2)octane (0.0785 g, 0.700 mmol) and acetonitrile (1.0 mL) were combined in a 10 mL roundbottom flask. The reaction flask was purged with N2, equipped with magnetic stirrer, and heated to 37° C. A solution of the product of Example 1434 (0.250 g, 0.432 mmol) in acetonitrile (2.50 mL) was added. After 2.5 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0200 g, 0.178 mmol) was added. After 64 hrs, 1,4-diazabicyclo(2.2.2)octane (0.0490 g, 0.437 mmol) was added. After 24 hrs, the reaction mixture was cooled to R.T. and concentrated in vacuo. The crude product was dissolved in acetonitrile (2.0 mL) and precipitated with ethyl ether (10.0 mL).

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The precipitate was filtered to yield a white solid. This trituration method was repeated, followed by concentrated in vacuo to give a white solid (0.185 g, 62percent). mp 218.0-225.0° C.; 1H NMR (CD3OD) δ 0.90 (m, 6H), 1.05-1.55 (m, 10H), 1.16 (t, J=6.6 Hz, 2H), 1.78 (m, 1H), 2.12 (m, 3H), 2.76 (s, 6H), 3.10 (m, 2H), 3.17-(t, J=7.2 Hz, 6H), 3.30-3.50 (m, 8H), 4.10 (s, 1H), 4.21 (t, J=5.4 Hz, 2H), 5.31 (s, 1H), 6.10 (s, 1H), 6.55 (d, J=7.2 Hz, 1H), 7.25 (d, J=6.9 Hz, 1H), 7.33-7.42 (m, 2H), 7.56 (s, 1H), 7.76 (d, J=9.0 Hz, 1H). HRMS. Calc'd for C36H55N4O5SCl: 655.3893. Found: 655.3880. Patent; G.D. Searle &amp; Co.; US2004/14803; (2004); (A1) English View in Reaxys [4R-[4a,5a(4R*,5R*)]]-N,N'-bis[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1benzothiepin-5-yl]phenoxy]pentyl]-N,N,N'N'-tetramethyl-1,6-hexanediaminium Dichloride [4R-[4a,5a(4R*,5R*)]]-N,N'-bis[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]pentyl]-N,N,N'N'-tetramethyl-1,6-hexanediaminium Dichloride The pentyl bromide intermediate (1.002 g, 1.64 mmol, obtained from Example 1418, Step 1) and N,N,N',N'-tetramethyl-1,6-hexanediamine (0.100 g, 0.580 mmol) in 5 mL of acetonitrile were placed in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer and heated to 50° C. After 15 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give an offwhite foamy solid (1.141 g). The solid was dissolved in acetonitrile and precipitated with ethyl ether. After cooling to 0° C., the solvent was decanted to yield a sticky off-white solid. This trituration method was repeated, and the resulting sticky solid was concentrated in vacuo to give the desired dibromide salt as an off-white foamy solid (0.843 g, quantitative): 1H NMR (CDCl3) δ 0.85 (m, 12H), 1.01-1.70 (m, 30H), 1.76-2.08 (m, 12H), 2.18 (t, J=12.3 Hz, 2H), 2.79 (s, 12H), 3.03 (ABq, 4H), 3.35 (s, 12H), 3.52 (br s, 6H), 3.72 (br s, 4H), 3.97 (br s, 4H), 4.08 (br s, 2H), 5.42 (s, 2H), 6.00 (s, 2H), 6.51 (d, J=9.0 Hz, 2H), 6.86 (d, J=7.8 Hz, 4H), 7.38 (d, J=7.8 Hz, 4H), 7.83 (d, J=8.7 Hz, 2H). Patent; G.D. Searle &amp; Co.; US2004/14803; (2004); (A1) English View in Reaxys 1.A.B : B. To a solution of 3-(2-hydroxy)ethyl-6-methoxy-2-methylbenzomiazolium bromide (4c, 0.79 g) in methanol (30 ml) was added an excess of ethyl N-phenylformimidate (1.5 g) and the solution was stirred at room temperature for 16 h. The solvent was removed under reduced pressure to yield a dry solid. The solid was subjected to column chromatography (silica gel), and eluted with a methanol/methylene chloride gradient (from 0 to 15percent methanol). The fractions containing the product were combined and concentrated to dryness under reduced pressure. The solid was dissolved in methanol (5 ml) and precipitated with ethyl ether (150 ml). Patent; Coulter International Corp.; EP1303751; (2005); (B1) English View in Reaxys 1.C : Example 1C To a solution of 3-(2-hydroxy)ethyl-2-methylbenzothiazolium bromide (11b, 1.19 g) in a mixed solvent of methanol/ ethanol (3:1, 80 mL) was added excess of ethyl N-phenylformidiate (3.0 g) and stirred at room temperature for 36 h. Evaporated off solvent under reduced pressure to dryness. The solid was subjected to column chromatography (silica gel, methylene chloride/methanol) purification. The fractions contained the product were combined and concentrated to dryness under reduced pressure. The solid was dissolved in methanol (10 mL) and precipitated with ethyl ether (200 mL). Patent; Coulter International Corp.; EP1303751; (2005); (B1) English View in Reaxys 13 : Tetravalent PEG 2'-urea conjugate of 4-(2'-amino-4'-guanidino-6'-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine (octa)-trifluoroacetate (Terminally branched with Lysine) Example 13 Tetravalent PEG 2'-urea conjugate of 4-(2'-amino-4'-guanidino-6'-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine (octa)-trifluoroacetate (Terminally branched with Lysine) To a solution of PEG35K-(NH2)2 (1 g, 28.6 mmol, NOF, Japan) and DMAP (0.035 mg, 0.286 mmol) in DCM (3.5 mL) at rt was added Boc-N-Lys(Boc)-N-hydroxy succinimide ester (102 mg, 0.229 mmol, Novabiochem). The viscous reaction mixture was stirred vigorously for 24 h then diluted with DCM and Et2O was added slowly to cloudiness.

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The mixture was allowed to stand at 4° C. until precipitation was complete. The solid was collected by filtration and the process was repeated 3 more times. A white solid was collected and treated with TFA (50percent in DCM) for 4 h at rt. The reaction mixture was concentrated to dryness and the residue was neutralized by adding excess DIEA and evaporating in vacuo to a give the desired intermediate as a solid. Following the same procedure described in Example 7, a portion of the recovered solid (300 mg, 0.0086 mmol) was reacted with 6-(3-{3'-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-4-(N,N'-bistert-butoxycarbonyl)-guanidino-6-methyl-biphenyl-2-yl}-ureido)-hexanoic acid (64 mg, 0.0686 mmol, as prepared in Example 2, step i), diisopropylcarbodiimide (10.6 μL, 0.068 mmol), and N,N-dimethylaminopyridine (16 mg, 0.129 mmol) in DCM (2 mL). The reaction mixture was concentrated and the residue was dissolved in a DCM/MeOH mixture and precipitated with Et2O (3*). Patent; Subasinghe, Nalin; Khalil, Ehab; Ali, Farah; Hufnagel, Heather Rae; Ballentine, Shelley; Travins, Jeremy M.; Leonard, Kristi A.; Bone, Roger F.; US2005/4031; (2005); (A1) English View in Reaxys 15.C : Synthesis of Polycations. C. Di-(2-methyl-4-hydroxymethyl(glyoxilic acid ester)-1,3-dioxolane)-1,4-benzene: 1,4-Bis(3-aminopropyl)piperazine Copolymer (1:1) (MC228): To a solution of di-(2-methyl4-hydroxymethyl(glyoxylic acid ester)-1,3-dioxolane) 1,4-benzene (100 mg, 0.273 mmol) in dimethylformamide was added 1,4-bis(3-aminopropyl)-piperazine (23 μL, 0.273 mmol, Aldrich Chemical Company) and the solution was heated to 80° C. After 16 h the solution was cooled to RT and precipitated with diethyl ether. The solution was decanted and the residue washed with diethyl ether (2*) and dried under vacuum to afford di-(2methyl-4-hydroxymethyl(glyoxylic acid ester)-1,3-dioxolane) 1,4-benzene: 1,4-bis(3-aminopropyl)-piperazine copolymer (1: 1). By similar methods the following polymers were constructed: Patent; Rozema, David B.; Budker, Vladimir G.; Hagstrom, James E.; Trubetskoy, Vladimir; Wolff, Jon A.; Monahan, Sean D.; Slattum, Paul M.; US2005/37496; (2005); (A1) English View in Reaxys 5.C : Synthesis of Polycations C. Di-(2-methyl-4-hydroxymethyl(glyoxilic acid ester)-1,3-dioxolane)-1,4-benzene:1,4-Bis(3-aminopropyl)piperazine Copolymer (1:1) (MC228): To a solution of di-(2-methyl-4-hydroxymethyl(glyoxylic acid ester)-1,3-dioxolane) 1,4-benzene (100 mg, 0.273 mmol) in dimethylformamide was added 1,4-bis(3-aminopropyl)-piperazine (23 μL, 0.273 mmol, Aldrich Chemical Company) and the solution was heated to 80° C. After 16 h the solution was cooled to RT and precipitated with diethyl ether. The solution was decanted and the residue washed with diethyl ether (2*) and dried under vacuum to afford di-(2methyl-4-hydroxymethyl(glyoxylic acid ester)-1,3-dioxolane) 1,4-benzene: 1,4-bis(3-aminopropyl)-piperazine copolymer (1:1). By similar methods the following polymers were constructed: Patent; Trubetskoy, Vladimir S.; Rozema, David B.; Monahan, Sean D.; Budker, Vladimir G.; Hagstrom, James E.; Wolff, Jon A.; US2004/162235; (2004); (A1) English View in Reaxys 6.d : d) d) mPEG20K Amide of 3-{[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-4-guanidino-6-methyl-biphenyl-2ylcarbamoylmethylsulfanyl}-propionic acid bis-trifluoroacetate To a solution of methanesulfonic acid {3'-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3sulfonyl]-4-(N,N'-bis-tert-butoxycarbonyl)-guanidino-6-methyl-biphenyl-2-ylcarbamoyl}-methyl ester (21 mg, 0.023 mmol, as prepared in Example 6, Route b, step c) and diisopropyl ethylamine (100 μL, 192 μmol) in DCM (1.5 mL) was added mPEG20K-NHC(O)(CH2)2-SH (350 mg, 16.7 μmol, Rapp Polymere GMBH, Tuebingen, Germany). The resulting solution was stirred at rt and reaction progress was monitored on TLC using Ellman's reagent (DTNB). After all free thiol was consumed (2 h), the reaction mixture was diluted with MeOH (3 mL) and then precipitated by slowly adding diethyl ether. Once the reaction mixture became cloudy, it was allowed to stand at 4° C. to induce complete precipitation. The solid was collected on a Buchner funnel and dried by suction.

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Patent; Subasinghe, Nalin; Khalil, Ehab; Ali, Farah; Hufnagel, Heather Rae; Ballentine, Shelley; Travins, Jeremy M.; Leonard, Kristi A.; Bone, Roger F.; US2005/4031; (2005); (A1) English View in Reaxys VI.F : Synthesis of L75 and L76 F. L75 (N-[2-[[[[4,7,10-Tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetyl]amino]methyl]benzoyl]-L-glutaminylL-tryptophyl-L-alanyl-L-valyl-glycyl-L-histidyl-L-L-leucyl-L-methioninamide) Resin I (0.5 g; 0.3 mmol) was shaken in a solid phase peptide synthesis vessel with 50percent morpholine in DMA (7 mL) for 10 min, the solution was emptied and fresh 50percent morpholine in DMA (7 mL) was added. The suspension was stirred for 20 min then the solution was emptied and the resin washed with DMA (5*7 mL). 2-[[[9H-Fluoren-9-ylmethoxy)carbonyl]amino]methyl]benzoic acid, E (0.45 g; 1.2 mmol), N-hydroxybenzotriazole (HOBt) (0.18 g; 1.2 mmol), N,N'-diisopropylcarbodiimide (DIC) (0.19 mL; 1.2 mmol) and DMA (7 mL) were added to the resin, the mixture shaken for 24 h at room temperature, the solution was emptied and the resin was washed with DMA (5*7 mL). The resin was then shaken with 50percent morpholine in DMA (7 mL) for 10 min, the solution was emptied, fresh 50percent morpholine in DMA (7 mL) was added and the mixture shaken for 20 min. The solution was emptied and the resin washed with DMA (5*7 mL). 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid tris(1,1-dimethylethyl)ester adduct with NaCl (DOTA tri-tbutyl ester) (0.79 g; 1.2 mmol), HOBt (0.18 g; 1.2 mmol), DIC (0.19 mL: 1.2 mmol), DIEA (0.40 mL; 2.4 mmol) and DMA (7 mL) were added to the resin. The mixture was shaken for 24 h at room temperature, the solution was emptied and the resin was washed with DMA (5*7 mL), CH2Cl2 (5*7 mL) and vacuum dried. The resin was shaken in a flask with reagent B (25 mL) for 4.5 h. The resin was filtered and the filtrate was evaporated under reduced pressure to afford an oily crude that after treatment with Et2O (20 mL) gave a precipitate. The resulting precipitate was collected by centrifugation and was washed with Et2O (3*20 mL) to give L75 (190 mg; 0.13 mmol) as a white solid. Yield 44percent. Patent; Cappelletti, Enrico; Lattuada, Luciano; Linder, Karen E.; Marinelli, Ed; Nanjappan, Palaniappa; Raju, Natarajan; Swenson, Rolf E.; Tweedle, Michael; US2004/136906; (2004); (A1) English View in Reaxys 95 mg 15 (55%)

10 : 6-(2-(1,3,3,5,7,7-hexamethyl-6-(2-(1,3,3-trimethyl-1,2,3,4-tetrahydrobenzo[h]quinazolin-3-ium-6-yl)vinyl)-3,7-dihydropyrrolo[2,3-f]indolediium-2-yl)vinyl)-1,3,3-tri methyl-1,2,3,4-tetrahydrobenzo[h]quinazolin-3ium di(4-methyl-1-benzene sulfonat) di(hexafluorophosphate) (15) 100 mg (0.25 mmol) of 6-formyl-1,3,3-trimethyl-1,2,3,4-tetrahydrobenzo[h]quinazolin-3-ium hexafluorophosphate 16 was dissolved in 5 ml of acetic anhydride, and 77 mg (0.125 mmol) of 1,2,3,3,5,6,7,7-octamethyl-3,7-dihydropyrrolo[2,3-f]indoledinium di(4-methyl-1-benzene sulfonate) 3b was added. The mixture was refluxed for 1 hour. After cooling the solvent was removed under reduced pressure and the residue treated with hexane, filtered and washed with hexane and Et2O. The solid was redissolved in a minimum volume of nitromethane and precipitated with Et2O. Yield: 95 mg 15 (55percent). UV: λmax (abs) 554 nm (MeOH). Patent; Terpetschnig, Ewald A.; US2007/281363; (2007); (A1) English View in Reaxys 14 : Preparation of Compound 17 Example 14 Preparation of Compound 17 To compound 16 (0.18 g, 0.48 mmol) was added compound 4 (0.14 g, 0.33 mmol), Pd(PPh3)4 (0.05 g, 0.49 mmol), and toluene (10 mL) in a sealed tube under an argon atmosphere. The solution was degassed with argon and heated at 135° C. in an oil bath for 3 h. The solution was cooled to room temperature, diluted with saturated NaHCO3, and extracted with CH2Cl2 (3*30 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give a light brown oil. The residue was purified by flash column chromatography using MeOH/CH2Cl2 (10percent) to afford 17 as a white solid. The sample was dissolved into hexane/CH2Cl2/MeOH and then precipitated with diethyl ether, filtered, and rinsed several times with ether to provide in 17 (30.3 mg): mp 95-100° C.; 1H NMR (300 MHz, CDCl3) δ 8.68 (d, 1 H), 7.96 (d, 2 H), 7.77-7.69 (m, 2 H), 7.49-7.45 (m, 3 H), 7.24-7.20 (m, 1 H), 5.99 (s, 1 H), 5.11 (s, 1 H), 4.88-4.83 (m, 3 H),

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4.65-4.56 (m, 1 H), 3.91-3.80 (m, 2 H), 3.65-3.60 (m, 1 H), 1.66-1.52 (m, 8 H), 1.05-0.99 (t, 3 H; IR (KBr) 3411, 2968, 1601, 1489 cm-1; CI MS m/z=432 [C24H29N7+H]+. Patent; AMR Technology, Inc.; US6969720; (2005); (B2) English View in Reaxys 1.2 : 1-2. The diethylether soluble extract was concentrated and dried to obtain 300 g of diethyl ether soluble extract of Salviae miltiorrhizae BGE. Patent; DIGITAL BIOTECH CO., LTD.; ILSUNG PHARMACEUTICALS CO., LTD.; US2009/312413; (2009); (A1) English View in Reaxys 3 : Synthesis of a CHI-PEOPPO-PEO Derivative EXAMPLE 3 Synthesis of a CHI-PEOPPO-PEO Derivative A synthesis carried out with a PEO of molar mass 2,000 g/mol, a CHI-PEOPPO with DS 0.1 and a PEO DS of ~0.25 is targeted. To a solution of poly(ethylene oxide) methyl monoether (2 g, 1 mmol) in a solution of anhydrous CH2Cl2/DMSO (97/3 (v/v), 100 mL) under nitrogen is slowly added a solution of Dess-Martin Periodinane (DMP) (0.424 g, 1 mmol) in DMSO (4 mL). The reaction medium is left under stirring for 2 hours at room temperature. The medium is concentrated with the rotary evaporator until a whitish oil is obtained. The residual oil precipitates from ethyl ether (600 mL). The raw product is isolated by filtration on a frit 4. Patent; Centre National De La Recherche Scientifique (CNRS); Universite Joseph Fourier-Grenoble 1; US2010/204177; (2010); (A1) English View in Reaxys 1 : Synthesis of Azido-Topotecan.HCl Synthesis of Azido-Topotecan.HCl A 500 mL single neck round-bottomed flask is charged with a rubber septum, a magnetic stir bar, and argon gas inlet. 10-MEM-topotecan.HCl.3H2O (13.3 mmol, prepared from topotecan and methoxyethoxymethyl chloride\triethylamine) and acetonitrile (MeCN 250 mL) are added to give a pale yellow suspended solution. All the volatiles are removed using a rotary evaporator to remove H2O from 10-MEM-topotecan by azeotropic evaporation. Azidoacetic acid (5.37 g, 53.2 mmol) is added and then dichloromethane (266 mL) is added to give a clear yellow solution. 4-(dimethylamino)pyridine (DMAP, 2.44 g, 20.0 mmol) is added and the mixture is cooled down to 0° C. A solution of dicyclohexylcarbodiimide (DCC 11.00 g, 53.2 mmol) in dichloromethane (10 mL) is added slowly. After stirring in the cold for 1 hour, the mixture is allowed to stir at room temperature for 16 hours. The mixture is filtered using a filter paper and the filtrate is poured into 0.5 N HCl solution (100 mL) to keep the solution acidic (pH ~3). The resulting solution is charged with NaCl (15.0 g, 15percent w/v water) and two layers are separated. The organic layer is collected and the aqueous layer is twice extracted with dichloromethane. The combined organic phases are dried over anhydrous sodium sulfate, filtered and concentrated to give the product containing some 10-MEM-topotecan. A 250 mL single neck round-bottomed flask with a magnetic stir bar is fitted with a rubber septum and then connected to an argon gas inlet. The crude product prepared above (azidoacetic acid (1.34 g, 13.3 mmol), and dichloromethane (200 mL) are added into the flask. DMAP (1.95 g, 16.0 mmol) and DCC (2.74 g, 13.3 mmol) are added at room temperature. After stirring overnight, the aqueous workup as described above is performed. After concentrating, the residue is dissolved in MeCN and the methoxyethoxymethyl group is removed under reflux with cerium (III) chloride and filtered. After the filtrate is concentrated, the residue is redissolved in dichloromethane and precipitated by adding into diethyl ether. The precipitated material is collected and dried in vacuo to give the product as a powder. The structure is confirmed by 1H-NMR (Varian, 500 MHz, 10 mg/mL CDCl3). Patent; Serina Therapeutics, Inc.; US2010/330023; (2010); (A1) English View in Reaxys

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2 : (R)-1-({6-[(2, 5-dihydroxybenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol (R)-1-({6-[(2, 5-dihydroxybenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol Reaction conditions: 155° C., 2 h. Liquid chromatography 1.5percent MeOH in CHCl3; crystallization from abs. diethylether; mp 162.4-163.6° C. 1H

NMR (CDCl3): 0.86 (3H, t, J=9.0), 1.45 (6H, dd, J=12.0, J'=0.8), 1.82 (1H, sep, J=12.0), 3.38-3.56 (2H, mt), 3.76

(1H, m, J=9.0), 4.59 (2H, qui, J=9.0), 4.58 (2H, s(br)), 5.80 (1H, d, J=15.0), 6.28 (1H, s), 6.32 (1H, d, J=7.5), 6.85 (1H, d, J=7.5), 7.52 (1H, s(br)), 7.79 (1H, s), 8.95 (1H, s(br)), 10.50 (1H, s(br)). 1H NMR (CDCl ): 10.9, 22.5, 25.0, 39.4, 46.4, 56.3, 68.5, 114.7, 116.0, 116.9, 117.2, 127.8, 134.6, 149.5, 151.3, 3 152.0, 155.8, 160.0 Patent; Zatloukal, Marek; Krystof, Vladimir; Havlicek, Libor; Popa, Igor; Dolezal, Karel; Strnad, Miroslav; Jorda, Radek; US2012/70512; (2012); (A1) English View in Reaxys 2 : (R)-1-({6-[(2,4-dihydroxybenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol (R)-1-({6-[(2,4-dihydroxybenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol Reaction conditions: 155° C., 2 h. Liquid chromatography 1.5percent MeOH in CHCl3; crystallization from abs. diethylether; mp 189-191° C. 1H

NMR (CDCl3): 0.90 (3H, t, J=9.0), 1.43 (6H, dd, J=12.0, J'=3.0), 1.82 (1H, sep, J=12.0), 3.38-3.56 (2H, mt), 3.78

(1H, m, J=9.0), 4.59 (2H, qui, J=9.0), 4.58 (2H, s(br)), 5.80 (1H, d, J=15.0), 6.28 (114, s), 6.32 (1H, d, J=7.5), 6.85 (1H, d, J=7.5), 7.52 (1H, s(br)), 7.79 (1H, s), 8.95 (1H, s(br)), 10.50 (1H, s(br)). 1H NMR (CDCl ): 10.9, 22.5, 25.0, 42.6, 46.4, 56.3, 68.5, 102.6, 108.2, 114.7, 118.3, 130.5, 134.6, 152.0, 155.7, 3 155.8, 158.4, 160.0 Patent; Zatloukal, Marek; Krystof, Vladimir; Havlicek, Libor; Popa, Igor; Dolezal, Karel; Strnad, Miroslav; Jorda, Radek; US2012/70512; (2012); (A1) English View in Reaxys 2 : (R)-1-({6-[(2-hydroxy-3-methylbenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol Reaction conditions: 160° C., 3 h. Liquid chromatography 1.5percent MeOH in CHCl3; crystallization from abs. diethylether; mp 145-147° C. 1H

NMR (CDCl3): 0.89 (3H, t, J=9.0), 1.46 (6H, dd, J=12.0, J'=3.0), 1.63 (1H, sep, J=12.0), 2.32 (3H, s), 2.54 (1H, s),

3.38-3.56 (2H, m), 3.76 (3H, s), 3.82 (1H, m), 4.58 (2H, qui, J=9.0), 4.62 (2H, s(br)), 6.76-6.83 (3H, m), 7.50 (1H, s(br)), 7.78 (1H, s), 9.32 (1H, s(br)). 1H NMR (CDCl ): 10.9, 16.6, 22.5, 25.0, 38.3, 46.4, 56.3, 68.5, 114.7, 119.2, 125.1, 125.8, 126.4, 129.4, 134.6, 3 152.0, 154.1, 155.8 Patent; Zatloukal, Marek; Krystof, Vladimir; Havlicek, Libor; Popa, Igor; Dolezal, Karel; Strnad, Miroslav; Jorda, Radek; US2012/70512; (2012); (A1) English View in Reaxys 2 : (R)-1-({6-[(2-hydroxy-4-methoxybenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol Reaction conditions: 160° C., 3 h. (R)-1-({6-[(2,3-dihydroxybenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol Reaction conditions: 155° C., 2 h. Liquid chromatography 1.5percent MeOH in CHCl3; crystallization from abs. diethylether; mp 182-183° C. 1H

NMR (CDCl3): 0.86 (3H, t, J=9.0), 1.46 (6H, dd, J=12.0, J'=3.0), 1.63 (1H, sep, J=12.0), 3.38-3.56 (2H, m), 3.82

(1H, m, J=9.0), 4.57 (2H, qui, J=9.0), 4.64 (2H, s(br)), 5.80 (1H, d, J=15.0), 6.55 (1H, t, J=11.0), 6.62-6.70 (2H, m), 7.50 (1H, s(br)), 7.79 (1H, s), 8.95 (1H, s(br)), 9.40 (1H, s(br)). 1H NMR (CDCl ): 10.55, 21.84, 21.93, 23.78, 45.75, 53.97, 62.84, 114.08, 118.59, 119.31, 126.92, 135.27, 142.93, 3 145.30, 154.28, 158.61 Patent; Zatloukal, Marek; Krystof, Vladimir; Havlicek, Libor; Popa, Igor; Dolezal, Karel; Strnad, Miroslav; Jorda, Radek; US2012/70512; (2012); (A1) English View in Reaxys 2 : (R)-1-({6-[(2-hydroxy-5-methylbenzyl)amino]-9-isopropyl-9H-purin-2-yl}amino)propan-2-ol Reaction conditions: 160° C., 3 h. Liquid chromatography 1.5percent MeOH in CHCl3; crystallization from abs. diethylether; mp 160.0-161.3° C.

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NMR (CDCl3): 0.89 (3H, t, J=9.0), 1.46 (6H, dd, J=12,0, J'=3.0), 1.63 (1H, sep, J=12,0), 2.32 (3H, s), 2.54 (1H, s),

3.38-3.56 (2H, m), 3.76 (3H, s), 3.82 (1H, m), 4.58 (2H, qui, J=9.0), 4.62 (2H, s(br)), 6.72 (1H, d, J=7.50), 6.77-6.80 (2H, m), 7.50 (1H, s(br)), 7.78 (1H, s), 9.50 (1H, s(br)). 1H NMR (CDCl ): 10.9, 20.5, 22.5, 25.0, 39.4, 46.4, 56.3, 68.5, 114.7, 118.3, 124.1, 127.4, 129.1, 133.2, 134.6, 3 152.0, 152.3, 155.8, 160.0 Patent; Zatloukal, Marek; Krystof, Vladimir; Havlicek, Libor; Popa, Igor; Dolezal, Karel; Strnad, Miroslav; Jorda, Radek; US2012/70512; (2012); (A1) English View in Reaxys 2 : (RS)-2-({6-[(2-hydroxy-3-methoxybenzyl)amino]-9-isopropyl-9-H-purin-2-yl}amino)butan-1-ol Reaction conditions: 160° C., 6 h. Liquid chromatography 1.5percent MeOH in CHCl3; crystallization from abs. CHCl3/abs. Et2O; mp 120-122° C. 1H

NMR (CDCl3): 0.86 (3H, t, J=9.0), 1.46 (6H, dd, J=12.0, J'=3.0), 1.63 (1H, sep, J=12,0), 2.54 (1H, s), 3.38-3.56

(2H, m), 3.76 (3H, s), 3.82 (1H, m), 4.58 (2H, qui, J=9.0), 4.62 (2H, s(br)), 5.85 (1H, d, J=15.0), 6.67 (1H, t, J=12.0), 6.76-6.87 (2H, m), 7.50 (1H, s(br)), 7.78 (1H, s), 9.32 (1H, s(br)). 13C NMR (CDCl ): 10.56, 21.95, 23.82, 54.01, 55.75, 62.92, 64.83, 110.73, 113.55, 118.43, 120.65, 126.78, 135.21, 3 144.01, 147.57, 150.55, 154.42, 158.74 Patent; Zatloukal, Marek; Krystof, Vladimir; Havlicek, Libor; Popa, Igor; Dolezal, Karel; Strnad, Miroslav; Jorda, Radek; US2012/70512; (2012); (A1) English View in Reaxys 1.10 : Step 10: Step 10: (3aR,7S,13Z,14aS,15aR,18S,21R,33aR)-25-methoxy-5,17,35-trioxo-1,2,3,3a,5,6,7,8,9,10,11,12,14a, 15,17,18,20,21,29,30,31,32,33,33a-tetracosahydro-7,19:18,21-dimethanocyclopenta[28,29]cyclopropa[12,13] [1,20,3,14,17]dioxatriazacyclononacosino[21,22-b]quinoxaline-15a(16H)-carboxylic acid To a solution of the product from step 9 (14.3 g, 19.54 mmol) in THF (200 mL), EtOH (50 mL), and H2O (100 mL) was added LiOH (4.68 g, 195 mmol). The mixture was heated to 40° C. for 4 hours, cooled to RT, and pH adjusted to 2 with 1N HCl. The resulting solid was collected by filtration, washed with H2O, and combined with the material isolated from the extraction of the aqueous layer. The aqueous layer was then extracted with EtOAc two times. The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo. The combined residues were then taken up in DCM and precipitated with Et2O to give, after filtration, the title compound as a solid. LRMS (ESI) m/z 704.6 [(M+H)+; calculated for C38H50N5Og 704.4]. in tetrahydrofuran, ethanol, water Patent; MERCK SHARP and DOHME CORP; Liverton, Nigel J.; McCauley, John A.; Rudd, Michael T.; US2012/121624; (2012); (A1) English View in Reaxys R.11 : Synthesis of Compound 19 Reference Example 11 Synthesis of Compound 19 A four-necked flask was added with 3.00 g (6.32 mmol) of compound 6c, and 60 mL of tetrahydrofuran, and argon bubbling was conducted at room temperature (25° C.) for 30 minutes. After cooling the reaction solution to -30° C., 1.01 g (5.69 mmol) of N-bromosuccinimide was added, and stirred at -10° C. for 2 hours. After stirring, disappearance of 90percent of starting material was confirmed by liquid chromatography, and the reaction was stopped. The reaction solution was added with water and diethylether, and the organic layer was extracted, and the organic layer was purified by a column using hexane as a developing solvent. The purified organic layer was dried to remove the solvent, and 2.84 g of compound 19 was obtained. 1H-NMR (CDCl , δ (ppm)): 0.83 (m, 18H), 1.08-1.47 (m, 20H), 1.95 (q, 4H), 6.65 (s, 1H), 6.66 (s, 1H), 6.98 (s, 1H) 3 With N-Bromosuccinimide in tetrahydrofuran Patent; SUMITOMO CHEMICAL COMPANY, LIMITED; Yoshimura, Ken; Ohya, Kenichiro; US2013/26459; (2013); (A1) English

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View in Reaxys 82 : Example 82 Example 82 Synthesis of mPEG12K-b- Poly-(d-Glu(OBn)1.5-co-Glu(OBn)1.5)-b-Poly (Tyr(OH)25-co-d-Phe15)-Ac The polymer from Example 81 was deprotected using the general method from example 74 only adjusting stoichometry. Once complete (3 hrs) the solution was rotovapped to a thick paste and then redissolved in dicholomethane and precipitated in cold Diethyl ether, collected by filtration and dried in vacuo. This reaction yielded 22 g of dry material (Yield = 76.92 percent). 1H NMR (d6-DMSO) δ 9.09, 8.50-7.75, 7.35-6.45, 5.04, 4.70-4.20, 3.91-3.05, 3.03-2.10,2.09-1.50. Patent; Intezyne Technologies Inc.; Sill, Kevin; Carie, Adam; Vojkovsky, Tomas; Semple, Edward J.; EP2660255; (2013); (A1) English View in Reaxys 85 : Example 85 Example 85 Synthesis of mPEG12K-b-Poly-(d-Glu(OBn)2.5-co-Glu(OBn)2.5)-b-Poly (Tyr(OH)25-co-d-Phe15)-Ac Using the general method from Example 74 and adjusting stoichiometry, the polymer from Example 84 was deprotected (32 g, 1.65 mmol). Once complete (3 Hrs.) the solution was rotovapped to a thick paste and then redissolved in DCM and precipitated in cold Diethyl ether, collected by filtration and dried in vacuo. This reaction yielded 27g of dry material (94.2 percent). 1H NMR (d6-DMSO) δ 9.09, 8.50-7.75, 7.35-6.45, 5.04, 4.70-4.20, 3.91-3.05, 3.03-2.10, 2.09-1.50. Patent; Intezyne Technologies Inc.; Sill, Kevin; Carie, Adam; Vojkovsky, Tomas; Semple, Edward J.; EP2660255; (2013); (A1) English View in Reaxys 88 : Example 88 Example 88 Synthesis of mPEG12K-b-Poly-(d-Glu(OBn)3.5-co-Glu(OBn)3.5)-b-Poly (Tyr(OH)25-co-d-Phe15)-Ac The polymer from Example 87 was deprotected using the general method from Example 74 only adjusting stoichometry (32 g, 1.61 mmol). Once complete (3 Hrs.) the solution was rotovapped to a thick paste and then redissolved in DCM and precipitated in cold Diethyl ether, collected by filtration and dried in vacuo. This reaction yielded 23g of dry material (80 percent). 1H NMR (d6-DMSO) δ 9.09 , 8.50-7.75, 7.35-6.45, 5.04, 4.70-4.20, 3.91-3.05, 3.03-2.10, 2.09-1.50. Patent; Intezyne Technologies Inc.; Sill, Kevin; Carie, Adam; Vojkovsky, Tomas; Semple, Edward J.; EP2660255; (2013); (A1) English View in Reaxys 106 : Example 106 Example 106 Synthesis of mPEG11.6K-b-Poly-(d-Glu(NHOH)5-co-Glu(NHOH)-b-Poly (Tyr(OH)10-co-d-Leu20-co-Asp10)-Ac Triblock ester from Example 105 was weighed (25 g, 1.38 mmol) into a clean 500mL round bottom flask and the polymer was dissolved completely in 200 mL of tetrahydrofuran. To this solution thirty equivalents of hydroxylamine (1.9 mL, .028 mmol) and lithium hydroxide monohydrate (1.16 g, 27.6 mmol) was stirred under nitrogen at room temp over night. Completion of the reaction was verified by 1H NMR. This solution was mixed with 100mL methanol and precipitated with diethyl ether (about 7 volumes). This white solid was collected by filtration and washed with fresh diethyl ether. The collected solid was then dissolved in acetone and and a catalytic amount of acetic acid was allowed to stir overnight. the solution was poured into a clean two liter beaker and diethyl ether was slowly added to the solution with stirring. This white solid was collected by filtration and then dried in vacuo. Yielded 22 g (92percent). 1H NMR (d6-DMSO)) δ 9.4-8.5, 8.40-7.71, 7.40-7.11, 6.93, 6.57, 5.10, 4.53-3.99, 3.86-3.02, 2.99-2.87, 2.09-1.19, 1.6-1.2, 1.01-0.5. With lithium hydroxide monohydrate, hydroxylamine in tetrahydrofuran, methanol

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Patent; Intezyne Technologies Inc.; Sill, Kevin; Carie, Adam; Vojkovsky, Tomas; Semple, Edward J.; EP2660255; (2013); (A1) English View in Reaxys 77 : Example 77 Example 77 Synthesis of mPEG12K-b-(d-Glu(NHOH)5-co-Glu(NHOH)-b-Poly (Tyr(OH)10-co-d-Leu20-co-Asp10)-Ac Triblock ester (Example 76) was weighed (20 g, 0.96 mmol) into a clean 500mL round bottom flask and 200 mL of tetrahydrofuran was added and dissolved completely. To this solution thirty equivalents of hydroxylamine (1.9 mL, 28 mmol) and 0.5 g of TBD catalyst was stirred under nitrogen at 50°C overnight. Completion was verified by 1H NMR. This solution was mixed with 100 mL methanol and precipitated with diethyl ether (about 7 volumes). This white solid was collected by filtration and washed with fresh diethyl ether. The collected solid was then dissolved in acetone and and a catalytic amount of acetic acid was allowed to stir overnight. The solution was poured into a clean two liter beaker and diethyl ether was slowly added to the solution with stirring. 1H NMR (d6-DMSO) δ 9.4-8.6, 8.51-7.77 , 7.44-7.57, 6.96, 6.56, 4.52-4.00 , 3.75-3.29, 3.03-2.45 , 2.08-1.21, 0.95-0.57. With hydroxylamine in tetrahydrofuran, methanol Patent; Intezyne Technologies Inc.; Sill, Kevin; Carie, Adam; Vojkovsky, Tomas; Semple, Edward J.; EP2660255; (2013); (A1) English View in Reaxys 1.b : Part (b): Part (b): Synthesis of PNIPAM43-SC(=S)SC4H9 by RAFT Polymerization NIPAM (15 g, 0.133 mol), RAFT agent (0.75 g 3.0*10-3 mol) and AIBN (50 mg, 3.0*10-4 mol) were dissolved in 30 ml DMSO in a 50 ml Schlenk flask. The solution was purged by Ar for 30 min. The reaction solution was then immersed in preheated oil-bath at 60° C. for 16 h. The reaction was stopped by cooling in ice-bath and exposing the solution to the air. The polymerization mixture was then diluted by 500 ml DCM and washed by Milli-Q water for three times. The organic phase was dried over MgSO4, filtered, concentrated and precipitated in diethyl ether. After filtration, the yellow powder was dried under vacuum at R.T. for 48 h. (Mn,GPC=4800). 1H

NMR (CDCl3, 298K, 500 MHz); 6.47 (b, -NH-C=O- of poly(NIPAM) repeating units), 3.97 (b, -NH-CH(CH3)2 of

poly(NIPAM) repeating units), 4.62 (b, 1H, -CH-SC(=S)S-C4H9), 3.97 (b, -NH-CH(CH3)2 of poly(NIPAM) repeating units), 3.66 (b, 3H, CH3O-RAFT residual group) 3.34 (b, 2H, -SC(=S)S-CH2C3H7), 1.06-2.45 (b, methylene and methine protons of poly(NIPAM) backbone), 1.12 (b, methyl protons of poly(NIPAM) repeating units), 0.90 (b, 6H, methyl protons of RAFT residual group). With 2,2'-azobisisobutyronitrile in dimethyl sulfoxide Patent; THE UNIVERSITY OF QUEENSLAND; Gray, Peter; Monteiro, Michael John; Munro, Trent Phillip; Prowse, Andrew Benjamin James; US2015/337128; (2015); (A1) English View in Reaxys 10 : Preparation of Yellow Compound 2A1 Example 10 Preparation of Yellow Compound 2A1 A solution of 2.0 g of compound 4A1 and 7.47 g of compound 5A1, prepared as described in example 5, are dissolved in 50 ml toluene under an argon atmosphere and treated with 0.6 ml of a solution of hexachloroplatinic acid in iso-propanol (10percent (w/v)) at 80° C. until a 29Si-NMR confirms the consumption of all Si-H moieties (ca. 24 h). The mixture is then cooled down and dropped into diethyl ether to precipitate the product. The resulting solid is taken up in dichloromethane and precipitated a second time with diethyl ether. This procedure is repeated a third time to yield 6.1 g of yellow compound 2A1. 1H-NMR (CDCl3, 300 MHz): δ 0.15 (s, 6H); 0.61 (t, 2H); 1.62 (quint, 2H); 2.48 (m, 4H); 2.94 (t, 2H); 2.72 (m, 4H); 7.21 (d, 1H); 7.25 (d, 2H); 7.42 (d, 2H); 7.78 (m, 2H); 8.67 (d, 2H); 9.76 (NH). 29Si-NMR (CDCl , 80 MHz): δ -109; +13. 3

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in isopropyl alcohol, toluene Patent; BASF SE; Oehrlein, Reinhold; Baisch, Gabriele; (69 pag.); US9228063; (2016); (B2) English View in Reaxys EXAMPLES Synthesis of PLGA-Tris-Asp: A mixture of PLGA-Tris (100 mg, 0.016 mmol) and DMAP (6.1 mg, 0.050 mmol) in dry CH2Cl2 was stirred for 30 min at room temperature. A solution of aspirin chloride (99.0 mg, 0.5 mmol) in CH2Cl2 was added drop wise to the reaction mixture. The reaction was stirred at room temperature for 24 h. The solvent was evaporated to dryness. The residue was dissolved in CH2Cl2, precipitated with diethyl ether and methanol (CH2Cl2:MeOH:diethyl ether: 1:5:4). This process was repeated 5 times. Yield, 94 mg, 90percent. 1H NMR (CDCl3, 400 MHz): δ ppm 7.90 (d), 7.60 (t), 7.19 (t), 7.03 (d), 5.21 (m), 4.82 (m), 3.24 (s), 1.88 (s), 1.58 (m). With dmap in dichloromethane Patent; UNIVERSITY OF GEORGIA RESEARCH FOUNDATION INC.; Dhar, Shanta; Pathak, Rakesh Kumar; (23 pag.); US2016/45445; (2016); (A1) English View in Reaxys EXAMPLES A solution of triethylamine (18.13 mg, 0.18 mmol) and Tris (22.0 mg, 0.18 mmol) in 10 mL DMF was added slowly to the above reaction mixture. This reaction mixture was kept at room temperature for 24 h with vigorous stirring. The solvent was evaporated to dryness. The residue was dissolved in CH2Cl2, filtered and precipitated with diethyl ether and methanol (CH2Cl2:MeOH:diethyl ether:1:5:4). This process was repeated 5 times. Yield, 190 mg, 37percent. 1H NMR (CDCl3, 400 MHz): δ ppm 5.20 (m), 4.81 (m), 4.28 (br), 3.66 (s), 1.56 (d). With triethylamine in dichloromethane, DMFA Patent; UNIVERSITY OF GEORGIA RESEARCH FOUNDATION INC.; Dhar, Shanta; Pathak, Rakesh Kumar; (23 pag.); US2016/45445; (2016); (A1) English View in Reaxys

Methoxy-polyethylene glycol succinimidyl propionic acid

Rx-ID: 10762855 View in Reaxys 489/630 Yield 92.1%

Conditions & References 4 : Methoxy-polyethylene glycol succinimidyl propionic acid, MPEG-SPA (5) EXAMPLE 4 Methoxy-polyethylene glycol succinimidyl propionic acid, MPEG-SPA (5) 3.4 g (1 mmole) of methoxypoly(ethylene glycol)propionic acid is dissolved in 20 ml of dichloromethane and 0.24 g of N-hydroxysuccinimide (2.1 mmole) to react in ice-bath (0° C.). 2.1 mmole of dicyclohexylcarbodiimide dissolved in 4 ml of dichloromethane is dissolved in the solution. After reaction, the solution is vibration stirred overnight at room temperature, eluted out solid by precipitation of ethyl ether, filtered to be vacuum dried to obtain 3.2 g of product with a yield of 92.1percent. 1H-NMR(400 MHz, CDCl3), δ (ppm): 2.81 ppm (t, 4H, -NHS), 2.92 ppm (t, 4H, -CH2-COO-), 3.2 ppm (s, -OCH3), 3.5 ppm (s, -OCH2CH2O-), 13C NMR (400 MHz, CDCl3), δ (ppm) 25.2, 25.3, 31.2, 58.8, 69.9, 71.1, 72.3, 166.7, 168.8, 169.4. Anal. Calcd. (found)C16H29N3O9: C, 55.23 (54.42); H, 9.1(9.17); N, 19.43 (19.25). Patent; Kaohsiung Medical University; US2006/154324; (2006); (A1) English View in Reaxys

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PEG acrylates

Rx-ID: 23858885 View in Reaxys 490/630 Yield 88%

Conditions & References 3 : Preparation of PEG-Acrylates Preparation of PEG-Acrylates PEG acrylates were produced under argon atmosphere by reacting an azeotropically dried toluene solution of the precursor polymers with acryloyl chloride, in presence of triethylamine (molar ratios: OH 1: acryloyl chloride 2: triethylamine 2.2). The reaction proceeded with stirring overnight in the dark at room temperature. The resulting pale yellow solution was filtered through a neutral alumina bed; after evaporation of the solvent, the reaction product was dissolved in dichloromethane, washed with water, dried over sodium sulphate and precipitated in cold diethyl ether. Yield: 88percent; conversion of OH to acrylate: 100percent (from 1H-NMR analysis) 1H-NMR (CDCl ): 3.6 (341H (14800 4 arm: 337H theor.), 230 (10000 4 arm: 227H theor.), or 210H (20000 8 arm: 3 227H theor.), PEG chain protons), 4.3 (t, 2H, -CH2-C2-O-CO-CH=CH2), 5.8 (dd, 1H, CH2=CCOO-), 6.1 and 6.4 (dd, 1H, C2=CH-COO-) ppm. FT-IR (film on ATR plate): 2990-2790 (υ C-H), 1724 (υ C=O), 1460 (υs CH2), 1344, 1281, 1242, 1097 (υas C-O-C), 952, 842 (υs C-O-C) cm-1. Patent; Eidgenossische Technische Hochschule Zurich; US2003/166833; (2003); (A1) English View in Reaxys (4R-cis)-N-[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxylpentyl]N'-ethyl-N,N,N',N'-tetramethyl-1,2-ethanediaminium dichloride

Rx-ID: 24006314 View in Reaxys 491/630 Yield 92%

Conditions & References 3 : Step 1 Step 3: Preparation of di-quaternary salt The mono-quaternary salt (0.933 g, 1.29 mmol, obtained from Step 2), iodoethane (0.300 mL/3.75 mmol), and acetonitrile (30.0 mL) were combined in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer, and heated to 50° C. After 24 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give a yellow foamy solid (1.166 g). The solid was dissolved in methylene chloride/acetonitrile and precipitated with ethyl ether. After cooling to 0° C. overnight, the resulting solid was filtered, washed with ethyl ether and concentrated in vacuo to yield the di-quaternary salt as an off-white solid (1.046 g, 92percent): 1NMR (CD3OD) δ 0.59 (t, 6H), 0.70-1.10 (m, 9H), 1.16 (t, 3H), 1.22-1.80 (m, 9H), 2.42 (s, 6H), 2.78 (d, 2H), 2.98 (s, 6H), 3.02 (s, 6H), 3.22-3.37 (m, 4H), 3.63-3.78 (m, 4H), 3.80 (s, 4H), 4.93 (s, 1H), 5.71 (s, 1H), 6.22 (dd, 1H), 6.61 (d, 2H), 7.02 (d, 2H), 7.40 (d, 1H). Patent; G.D. Searle and Co.; US2002/13476; (2002); (A1) English View in Reaxys (4R-cis)-N-[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl ]phenoxy]pentyl]N'-ethyl-N,N,N',N'-tetramethyl-1,2-ethanediaminium dichloride

Rx-ID: 24075431 View in Reaxys 492/630 Yield 92%

Conditions & References 3 : Step 3 Step 3 Preparation of Di-quaternary Salt The mono-quaternary salt (0.933 g, 1.29 mmol, obtained from Step 2), iodoethane (0.300 mL/3.75 mmol), and acetonitrile (30.0 mL) were combined in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer, and heated to 50° C. After 24 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give a yellow foamy solid (1.166 g). The solid was dissolved in methylene chloride/acetonitrile and precipitated with ethyl ether.

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After cooling to 0° C. overnight, the resulting solid was filtered, washed with ethyl ether and concentrated in vacuo to yield the di-quaternary salt as an off-white solid (1.046 g, 92percent): 1H NMR (CD3OD) δ0.59 (t, 6H), 0.70-1.10 (m, 9H), 1.16 (t, 3H), 1.22-1.80 (m, 9H), 2.42 (s, 6H), 2.78 (d, 2H), 2.98 (s, 6H), 3.02 (s, 6H), 3.22-3.37 (m, 4H), 3.63-3.78 (m, 4H), 3.80 (s, 4H), 4.93 (s, 1H), 5.71 (s, 1H), 6.22 (dd, 1H), 6.61 (d, 2H), 7.02 (d, 2H), 7.40 (d, 1H). Patent; G.D. Searle and Co.; US6387924; (2002); (B2) English View in Reaxys

MPN-GThr-(R,S)MLys-Pro-Gln-OH

Rx-ID: 24520407 View in Reaxys 493/630 Yield 95%

Conditions & References 3.G : EXAMPLE 3 G) The retro-inverted tetrapeptide under F) (2.13 g, 1.87 mmoles) was dissolved in methylene chloride/TFA (1:1 v/v, 40 ml) at room temperature. After 90 minutes, the solvent was evaporated, the crude precipitated by addition of ethyl ether. Thus 1.416 g of MPN-gThr-(R,S)mLys-Pro-Gln-OH were obtained (yield: 95percent). HPLC [gradient (I) (230 nm)]: r.t. 12.4 minutes; purity: 91.5percent. Patent; Italfarmaco S.p.A.; US5521159; (1996); (A1) English View in Reaxys 5'-O-t-butyldiphenylsilyl-N4,3'-O-diacetyl2'-deoxy-2'-methylidenecytidine

Rx-ID: 24822629 View in Reaxys 494/630 Yield 89%

Conditions & References 11 : Example 11 Example 11 N4,3'-O-Diacetyl-2'-deoxy-2'-methylidenecytidine 5'-O-t-Butyldiphenylsilyl-2'-deoxy-2'-methylidenecytidine, 843 mg (1.64 mM) was 10 ml of pyridine, 1.5 ml of acetic anhydride was added thereto, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution to stop reaction, and then, the solvent was distilled off under reduced pressure. The resulting residue was partitioned with a mixture solvent of diethylether and aqueous saturated solution of sodium bicarbonate and the organic layer was distilled off to give a crude product of 5'-O-t-butyldiphenylsilyl-N4,3'-O-diacetyl2'-deoxy-2'-methylidenecytidine in an amount of 870 mg (yield: 89percent). Patent; Yamasa Shoyu Co., Ltd.; Yoshitomi Pharmaceutical Industries, Ltd.; US5026835; (1991); (A1) English View in Reaxys ethyl 5,6-methylenedioxy-(1,2,3,4-tetrahydronaphthylene)-1-carboximidate

Rx-ID: 24982352 View in Reaxys 495/630 Yield 87%

Conditions & References 8 : Ethyl 5,6-methylenedioxy-(1,2,3,4-tetrahydronaphthylene)-1-carboximidate EXAMPLE 8 Ethyl 5,6-methylenedioxy-(1,2,3,4-tetrahydronaphthylene)-1-carboximidate The product from Example 7 (3.8 g) was dissolved in absolute ethanol (30 ml) and diethylether (60 ml) and the imino ether formed as in Example 3 affording the product in 87percent yield; m.p. 185°-87° C. Patent; Abbott Laboratories; US4634705; (1987); (A1) English View in Reaxys Ethyl 5,6-methylenedioxy-(1,2,3,4-tetrahydronaphthylene)-1-carboximidate

Rx-ID: 25414452 View in Reaxys 496/630 Yield 87%

Conditions & References 8 : Ethyl 5,6-methylenedioxy-(1,2,3,4-tetrahydro-naphthylene)-1-carboximidate

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Example 8 Ethyl 5,6-methylenedioxy-(1,2,3,4-tetrahydro-naphthylene)-1-carboximidate The product from Example 7 (3.8 g) was dissolved in absolute ethanol (30 ml) and diethylether (60 ml) and the imino ether formed as in Example 3 affording the product in 87percent yield; m.p. 185-7°. Patent; ABBOTT LABORATORIES; EP166937; (1991); (B1) English View in Reaxys (4R-cis)-N-[5-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]pentyl]N'-ethyl-N,N,N',N'-tetramethyl-1,2-ethanediaminium dichloride

Rx-ID: 25783000 View in Reaxys 497/630 Yield 92%

Conditions & References 3 : Step 3 Step 3 Preparation of Di-Quaternary Salt The mono-quaternary salt (0.933 g, 1.29 mmol, obtained from Step 2), iodoethane (0.300 mL/3.75 mmol), and acetonitrile (30.0 mL) were combined in a 4 oz. Fischer Porter bottle. The reaction vessel was purged with N2, sealed, equipped with magnetic stirrer, and heated to 50° C. After 24 hours, the reaction mixture was cooled to ambient temperature and concentrated in vacuo to give a yellow foamy solid (1.166 g). The solid was dissolved in methylene chloride/acetonitrile and precipitated with ethyl ether. After cooling to 0° C. overnight, the resulting solid was filtered, washed with ethyl ether and concentrated in vacuo to yield the di-quaternary salt as an off-white solid (1.046 g, 92percent): 1H NMR (CD3OD) δ 0.59 (t, 6H), 0.70-1.10 (m, 9H), 1.16 (t, 3H), 1.22-1.80 (m, 9H), 2.42 (s, 6H), 2.78 (d, 2H), 2.98 (s, 6H), 3.02 (s, 6H), 3.22-3.37 (m, 4H), 3.63-3.78 (m, 4H), 3.80 (s, 4H), 4.93 (s, 1H), 5.71 (s, 1H), 6.22 (dd, 1H), 6.61 (d, 2H), 7.02 (d, 2H), 7.40 (d, 1H). Patent; G.D. Searle &amp; Co.; US2004/14803; (2004); (A1) English View in Reaxys

bis TFA salt

Rx-ID: 28805610 View in Reaxys 498/630 Yield 99%

Conditions & References 2.A.A : Step 5A Step 5A A solution of the product from step 4A (950 mg, 1.20 mmol) in DCM (75 mL) was treated with TFA (25 mL) slowly to control CO2 gas from vigorously bubbling. After stirring at rt for 1.5 hr, the solvent was concentrated to give a light brown slurry and Et2O was added to effect a precipitation. The light brown product (1.10 g, 99percent yield) bis TFA salt was obtained by a vacuum filtration and used without further purification. LC-MS (MS m/z 690 (M++1)). Patent; Bristol-Myers Squibb Company; US2009/285774; (2009); (A1) English View in Reaxys

azido-irinotecan.HCl Rx-ID: 29961284 View in Reaxys 499/630

Yield 95%

Conditions & References 14 : Synthesis of Azido-Irinotecan.HCl Synthesis of Azido-Irinotecan.HCl A 500 mL single neck round-bottomed flask was fitted with a rubber septum, a magnetic stir bar, and argon gas inlet. Irinotecan.HCl.3H2O (9.00 g, 13.3 mmol) and MeCN (250 mL) were added to give a pale yellow suspension. All the volatiles were removed using a rotary evaporator. Azidoacetic acid (5.37 g, 53.2 mmol) was added and dichloromethane (266 mL) was added to give a clear yellow solution. 4-(Dimethylamino)pyridine (DMAP, 2.44 g, 20.0 mmol) was added and the mixture was cooled to 0° C. A solution of DCC (11.0 g, 53.2 mmol) in dichloromethane (10 mL) was added. After stirring in the cold for 1 hour, the mixture was allowed to stir at room temperature for 16 hours.

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The mixture was filtered and the filtrate was poured into 0.5 N HCl (100 mL) to keep the solution acidic (pH ~3). The resulting solution was charged with NaCl (15.0 g, 15percent w/v water) and two layers were separated. The organic layer was collected and the aqueous layer was extracted twice with dichloromethane. The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated to give a pale yellow powder containing ~20percent of irinoteca.HCl. A 250 mL single neck round-bottomed flask with a magnetic stir bar was fitted with a rubber septum and then connected to an argon gas inlet. The crude product prepared above (9.1 g), azidoacetic acid (1.34 g, 13.3 mmol), and dichloromethane (200 mL) were placed in a flask and DMAP (1.95 g, 16.0 mmol) and DCC (2.74 g, 13.3 mmol) were added at room temperature. After stirring overnight, the aqueous workup described above was performed. After concentrating, the residue was dissolved in MeCN and filtered. After the filtrate was concentrated, the residue was dissolved in dichloromethane and precipitated by adding into diethyl ether. The precipitated material was collected and dried in vacuo to give 8.9 g (95percent yield) of desired product as pale yellow powder. 1H-NMR (Varian, 500 MHz, 10 mg/mL CDCl3) showed a significant chemical shift change of proton on C5 from 7.64 ppm (s, 1H) to 7.21 ppm (s, 1H) and the azidoacetyl proton peak at 4.09 ppm (m, 2H, N3CH2C(=O)O-) due to the conjugation of hydroxyl group of C4 with azidoacetic acid. Patent; Serina Therapeutics, Inc.; US2010/330023; (2010); (A1) English View in Reaxys

O HO

Rx-ID: 23858883 View in Reaxys 500/630 Yield

Conditions & References

87%

P.2 : Preparative Example 2 Preparative Example 2 Preparation of 1-(4-fluoro-n-butyl)piperazine trifluoroacetic acid (a compound of the formula (5a) wherein n=4, m=0, Z=F) A mixture of 1-tert-butoxycarbonyl-4-(4-fluoro-n-butyl)piperazine (3.50 g, 10.74 mmol) in trifluoroacetic acid (20 mL) was stirred at room temperature for 1 h. The reaction mixture was evaporated to dryness under vacuum and the resulting residue was triturated from Et2O to afford the titled compound (2.61 g, 87percent) as a white solid. mp 108.5-109.5° C; IR (neat) 1665 (C=O), 1118 (C-F) cm-1; 1NMR (CDCl /TMS) δ1.58-1.78 (m, 4H, NCH CH CH CH F), 3.11 (t, J=6.9 Hz, NCH CH ), 3.30-3.50 (m, 8 H, 2 3 2 2 2 2 2 2 NCH2 and 2 BocNCH2), 4.46 (dt, J=47.7 Hz, 5.4 Hz, 2 H, CH2CH2F); MS (FAB) m/z 161 (MH+). Patent; Kim, Dae-Kee; Lee, Ju Young; Ryu, Do Hyun; Lee, Nam Kyu; Lee, Suk Ho; Kim, Nam-Ho; Kim, JaeSun; Ryu, Je Ho; Choi, Jin-Young; Im, Guang-Jin; Choi, Won-Son; Kim, Tae Kon; Cha, Hoon; US2003/171361; (2003); (A1) English View in Reaxys

N F

2 HCl NH O

Rx-ID: 23858884 View in Reaxys 501/630 Yield 97%

Conditions & References P.4 : Preparative Example 4 Preparative Example 4 Preparation of 1-(2-fluoroethyl)homopiperazine dihydrochloride (a compound of the formula (5a) wherein n=2, m=1, Z=F) A mixture of 1-tert-butoxycarbonyl-4-(2-fluoroethyl)homopiperazine (550 mg, 2.23 mmol) in 10percent aqueous hydrochloric acid (2 ml) and tetrahydrofuran (4 mL) was stirred at room temperature for 2 h, and the reaction mixture was evaporated to dryness under vacuum. Resulting residue was triturated from Et2O/MeOH to afford the titled compound (475 mg, 97percent) as a white solid.

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mp 185-186° C.; IR (neat) 1069 (C-F) cm-1; 1H NMR (DMSO-d ) δ2.06-2.14 (m, 2H, NCH CH CH N), 3.16-3.76(m, 10 H, 5 NCH ), 4.54(dt, J=47.1 Hz, 5.7 Hz, 2 6 2 2 2 2 H, NCH2CH2F), 9.57(br s, 1 H, NH+), 9.91 (br s, 1 H, NH+), 11.70 (br s, 1 H, NH+); MS (FAB) m/z 147 (MH+). Patent; Kim, Dae-Kee; Lee, Ju Young; Ryu, Do Hyun; Lee, Nam Kyu; Lee, Suk Ho; Kim, Nam-Ho; Kim, JaeSun; Ryu, Je Ho; Choi, Jin-Young; Im, Guang-Jin; Choi, Won-Son; Kim, Tae Kon; Cha, Hoon; US2003/171361; (2003); (A1) English View in Reaxys meso-tetrakis[3-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)-2,4,6-trimethylphenyl]porphyrinato diaqua-manganese (III) pentaacetate

Rx-ID: 24075434 View in Reaxys 502/630 Yield 84%

Conditions & References 6.2 : 6.2. 6.2. Synthesis of meso-tetrakis[3-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)-2,4,6-trimethylphenyl]porphyrinato diaqua-manganese (III) pentaacetate, Structural Formula VII To a solution of 0.40 g (0.16 mmol) of Structural Formula x in 25 mL of methanol, 11.8 g of AG1-X8 acetate form resin was added. The mixture was stirred 3 h at room temperature. The resin was filtered off and washed several times with a large quantity of methanol. The filtrate was then concentrated under vacuum. The residue was dissolved in a minimum quantity of methanol and precipitated by adding a large excess of diethylether. The precipitate was filtered, washed with diethylether and dried under vacuum overnight leaving a dark green powder: 0.28 g (84percent yield). UV-visible (H2O) λ(ε mol-1 L cm-1): 378 (51.4*103), 398 (53.8*103), 466 (118.6*103), 566 (13.4*103), 596 (8.3*103). Anal.: Calc for C94H135N12O18S4Mn.7H2O: C, 55.61; H, 7.40; N, 8.28. Found: C, 55.31; H, 7.42; N, 8.66. MS (ES), m/z 1622.8 (C83H114N12O10S4Mn, z=1). Patent; Eukarion, Inc.; US6403788; (2002); (B1) English View in Reaxys meso-tetrakis[4-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)phenyl]porphyrinato diaqua-manganese (III) pentaacetate

Rx-ID: 24075435 View in Reaxys 503/630 Yield 76%

Conditions & References 5.2 : 5.2. 5.2. Synthesis of meso-tetrakis[4-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)phenyl]porphyrinato diaquamanganese (III) pentaacetate, Structural Formula VI To a solution of 0.52 g (0.24 mmol) of Structural Formula ix in 25 mL of methanol, 16.5 g of AG1-X8 acetate form resin was added. The mixture was carefully stirred 3 h at room temperature. The resin was filtered and washed several times with a large quantity of methanol. The filtrate was then concentrated under vacuum. The residue was dissolved in a minimum quantity of methanol and precipitated by adding a large excess of diethylether. The precipitate was filtered, washed with diethylether and dried under vacuum overnight leaving a dark green powder, Structural Formula VI: 0.37 g (76percent yield). UV-visible (H2O) λ(ε mol-1 L cm-1): 378 (57.9*103), 400 (59.0*103), 466 (104.6*103), 562 (13.7*103), 592 (8.9*103). Anal.: Calc for C82H111N12O18S4Mn.6H2O: C, 53.41; H, 6.72; N, 9.11. Found: C, 53.23; H, 7.00; N, 9.60. MS (ES), m/z 1453.5 (C71H90N12O10S4Mn, z=1). Patent; Eukarion, Inc.; US6403788; (2002); (B1) English View in Reaxys

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O O

NH 2 O O

Rx-ID: 24294565 View in Reaxys 504/630 Yield

Conditions & References

98%

11.A : N-(2-Aminoethyl-4-[(fluoren-9-yl)methoxy-carbamoylmethyl]benzamide.HCl A. A solution of 9-fluorenylmethyl chloroformate (5 g, 19 mmoles) in THF (50 ml) was added slowly to a solution of 4aminomethyl benzoic acid (2.9 g, 19 mmoles). The reaction mixture was stirred at room temperature for 3 hours, then acidified with 1N HCl, and THF was evaporated in the cold. The aqueous phase was extracted with ethyl acetate, the combined organic phases were dried over anhydrous sodium sulfate and the solvent was evaporated off. The resulting crude was treated with warm ethyl ether and filtered to give 7 g of 4-[(fluoren-9-yl)methoxy-carbamoylmethyl]benzoic acid (98percent yield); m.p.=232-235° C. 1 H-NMR d 12.7 (s, 1H, exchange with D O), 7.94 (m, 5H), 7.77 (d, 2H), 7.58+7.30 (m, 6H), 4.42 (d, 2H), 4.30 (m, 2 3H). Patent; Italfarmaco S.p.A.; US6034096; (2000); (A1) English View in Reaxys

H N

OH O

O F

Rx-ID: 25414450 View in Reaxys 505/630 Yield 85%

Conditions & References 30 : Example 30 Example 30 Preparation of 7-(1-acetamino-5-azaspiro[2,4]heptane-5-yl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3carboxylic acid 375mg of 7-(1-amino-5-azaspiro[2,4]heptane-5-yl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid was dissolved in a solvent containing 5m of pyridine and 4.5m of acetic anhydride; and the resulting solution was stirred at a room temperature over night and evaporated under a reduced pressure to remove the solvent. The residue was dissolved in 2m of dichloromethane and 0.5m of methanol and precipitated by adding 50m of ethylether. The precipitate was filtered and dried under a reduced pressure to obtain 355mg of desired compound(yield: 85percent). m.p.: 190~193°C Patent; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; EP550016; (1993); (A1) English View in Reaxys

cyclo-(Gly-Orn(Z)-Cyc(Ts)-Gly-Gly-)

Rx-ID: 25858208 View in Reaxys 506/630 Yield 78%

Conditions & References 1.L : L. L. Synthesis of cyclo-(Gly-Orn(Z)-Cyc(Ts)-Gly-Gly-) A solution of Gly-Orn(Z)-Cyc(Ts)-Gly-Gly-OH TFA salt (5.0 g, 6.23 mmol) in dry degassed DMF (1520 mL) was treated with TEA (1.74 mL, 12.5 mmol) and cooled to -40° C. DPPA (1.64 mL, 7.60 mmol was added dropwise over 10 min and the reaction was stirred at -40° C. for 3 hr thereafter. After this time the reaction was place in a -2° C. bath and allowed to stand at this temperature for 16 h thereafter.

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Water (1520 mL) was added and the resulting solution was stirred with mixed bed ion-exchange resin (750 g) for 6 h at RT. The resin was filtered and the solution was concentrated to a volume of -100 mL (DMF). The addition of ethyl ether (500 mL) produced a solid residue which was redissolved in methanol (100 mL) and again precipitated by the addition of ethyl ether (500 mL). Filtration afforded 3.26 g (78percent yield) of product as a white powder: 1H NMR (CDCl3) δ 0.96-2.10 (complex m, 14H), 2.37 (bs, 3H), 2.68-3.05 (m, 3H), 3.42-3.90 (complex m, 8H), 4.14 (m, 1H), 4.20 (m, 1H), 4.97-5.08 (m, 3H), 6.42 (d, J=8.4 Hz, 1H), 7.19 (d, J=8.0 Hz, 1H), 7.20-7.39 (m, 7H), 7.65-7.78 (m, 2H), 9.15 (bs, 1H), 9.22 (bs, 1 H); MS(HRFAB) m/z 671.2842 (M+H)+; 671.2863 calculated for C32H43N6O8S. Patent; MetaPhore Pharmaceuticals, Inc.; US2004/57904; (2004); (A1) English View in Reaxys F O

O Cl

Rx-ID: 40762562 View in Reaxys 507/630 Yield

Conditions & References Compound A1: 2-Benzyloxy-1-chloromethyl-4-fluoro-benzene Compound A1: 2-Benzyloxy-1-chloromethyl-4-fluoro-benzene To a solution of compound A1-4 (42.4 g, 182 mmol) in CH2Cl2 (210 mL) was added dropwise thionyl chloride (15.6 mL, 219 mmol) at 0° C. during 7 min period, and then added DMF (1 drop). After stirring at rt for 30 min, the solvent was concentrated in vacuo. To the resulting residue were added cold-water (100 mL) and Et2O (200 mL), and the mixture was neutralized to pH 7.2 with sat. NaHCO3 solution. After neutralizing, the mixture was extracted with Et2O several times. The combined organic layers were washed with water and brine, then dried over Na2SO4. The solvent was concentrated in vacuo to give a crude product. The crude product was purified by crystallization with n-Hexane to give 41.7 g of compound A-1 (yield=89.0percent) as a pale yellow powder. 1H NMR. (CDCl ) δ 7.47-7.29 (m, 6H), 6.65 (m, 2H), 5.12 (s, 2H), 4.66 (s, 2H). 3 With thionyl chloride in dichloromethane, N,N-dimethyl-formamide Patent; ViiV Healthcare Company; Shionogi and Co., Ltd.; JOHNS, Brian Alvin; BOROS, Eric Eugene; KAWASUJI, Takashi; KOBLE, Cecilia S.; KUROSE, Noriyuki; MURAI, Hitoshi; SHERRILL, Ronald George; WEATHERHEAD, Jason G.; US2015/225399; (2015); (A1) English View in Reaxys

H N

Cl S

O Br

Rx-ID: 24006315 View in Reaxys 508/630 Yield 80%

Conditions & References E.3.ii : N-[3-(2',4'-Diamino-[2,5']bithiazolyl-4-yl)phenyl]-5-chloro-thiophene-2-carboxamide Step (ii): A solution of 5-chloro-thiophene-2-carboxylic acid (3-acetyl-phenyl)-amide (2.0 g, 7.17 mmol) and CuBr2 (3.19 g, 14.34 mmol) in EtOAc (100 ml) was heated to reflux. Progress of the reaction was monitored every 30 minutes by TLC. After 2.5 h, starting material was still present, so additional CuBr2 (0.75 g) was added. After an additional 1.5 h, TLC indicated that all starting material had been consumed. The reaction was reduced in volume by 50percent in vacuo, diluted with CH2Cl2 (50 mL), filtered through a plug of silica, which was eluted with 40percent ethyl acetate/CH2Cl2 (300 mL). The resulting solution was concentrated in vacuo, giving a colorless oil, which was taken up in CH2Cl2 (2 mL) and precipitated with diethyl ether (10 mL), giving 5-chloro-thiophene-2-carboxylic acid (3-bromoacetyl-phenyl)-amide (2.06 g, 80percent yield) as white powder.

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The title compound was prepared as follows. Patent; Agouron Pharmaceuticals, Inc.; US2002/25976; (2002); (A1) English View in Reaxys meso-tetrakis[3-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)-2,4,6-trimethylphenyl]porphyrinato diaqua-iron(III) pentaacetate

Rx-ID: 24075433 View in Reaxys 509/630 Yield 67%

Conditions & References 7.2 : 7.2. 7.2. Synthesis of meso-tetrakis[3-(N-(2-(N,N,N-diethylmethylammonio)ethyl)aminosulfonyl)-2,4,6-trimethylphenyl]porphyrinato diaqua-iron(III) pentaacetate, Structural Formula VIII To a solution of 0.37 g (0.15 mmol) of Structural Formula xi in 20 mL of methanol, 10.5 g of AG1-X8 acetate form resin was added. The mixture was carefully stirred 3 h at room temperature. The resin was filtered and washed several times with a large quantity of methanol. The filtrate was then concentrated under vacuum. The residue was dissolved in a minimum quantity of methanol and precipitated by adding a large excess of diethylether. The precipitate was filtered, washed with diethylether and dried under vacuum overnight leaving a dark brown powder, Structural Formula VIII: 0.22 g (67percent yield). UV-visible (H2O) λ(ε mol-1 L cm-1): 330 (39.6*103), 416 (105.9*103). Anal.: Calc for C94H135N12O18S4Fe.12H2O: C, 53.22; H, 7.55; N, 7.92. Found: C, 52.66; H, 7.28; N, 7.98. MS (ES), m/z 768.5 (z=2), 517.5 (z=3). Patent; Eukarion, Inc.; US6403788; (2002); (B1) English View in Reaxys Homopolymer of benzenemethanaminium,N,N-dimethyl,N-methacryloxyethyl]-ethyl-3,4-{2-[tris(trimethylsiloxyl)silyl]ethyl},-chloride [VA]

Rx-ID: 24461541 View in Reaxys 510/630 Yield 70%

Conditions & References 11 : Homopolymer of benzenemethanaminium,N,N-dimethyl,N-methacryloxyethyl]-ethyl-3,4-{2-[tris(trimethylsiloxyl)silyl]ethyl},-chloride [VA] EXAMPLE 11 Homopolymer of benzenemethanaminium,N,N-dimethyl,N-methacryloxyethyl]-ethyl-3,4-{2-[tris(trimethylsiloxyl)silyl]ethyl},-chloride [VA] Dioxane was used as a solvent for all polymerizations, before use it was freshly distilled from LiAlH4. Benzene-methanaminium,N,N-dimethyl,N-methacryloxyethyl-3,4-{2-[tris(trimethylsiloxyl)silyl]ethyl},-chloride, 1.0 g was added to a clean, dry 20 ml glass, screw top test tube along with 10 ml dioxane, 10mg of azobisisobutylonitrile. After degassing with Argon the tube was capped and placed in an oil bath at 60° C. for one hour and then the temperature was raised to 70° C. and the polymerization was allowed to proceed overnight. A white precipitate was formed that was dissolved in methanol and precipitated from ethyl ether. A 70percent yield of polymer was obtained. The homopolymer was essentially insoluble in water but was soluble in methanol, dimethyl formamide and other polar organic solvents. The structure was confirmed by the following peaks in IR: 3400 CM-1, 1730 (ester), and 1060 (Si--O). Patent; Alcon Laboratories, Inc.; US5399737; (1995); (A1) English View in Reaxys Cl Cl Cl

OH H N

Cl Cl

Rx-ID: 25147481 View in Reaxys 511/630 Yield 71%

Conditions & References 1 : (1a)

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Molecular weight=532.40 43 mmol H--Arg--pNA.2HBr dissolved in 120 ml DMF is neutralized in cold (-10° C.) with Et3 N. The Et3 N.HBr formed is filtered off, whereafter 43 mmol Box--Gly--OH, 45 mmol HOBT and 50 mmol DCCI are added. The reaction goes on during stirring for 1 hour in cold and at room temperature overnight. The DCU formed is filtered off and the solution is evaporated in vacuo to an oil which is dissolved in 160 ml EtOAc, is washed with 2percent NaHCO3, H2 O, 2percent KHSO4 and H2 O. After drying with Na2 SO4 the EtOAc-phase is evaporated and precipitated with diethylether. Yield: 71percent TLC: Rf=0.23 (Pa6). Patent; KabiVitrum AB; US4797472; (1989); (A1) English View in Reaxys 20 : (20a) Molecular weight=438.33 5 mmol Boc--SarOH, 5 mmol HOBT and 6 mmol DCCI are added to 5 mmol H--Arg--pNA.2HCl dissolved in 25 ml DMF and neutralized in cold (-10° C.) with Et3 N. The mixture is stirred for 1 hour in cold and at room temperature overnight. The DCU formed is filtered off and the solution is evaporated in vacuo to an oil, which is dissolved in 100 ml n-butanol, washed with 2percent NaHCO3, H2 O, 2percent KHSO4 and H2 O. After drying with Na2 SO4, the n-butanol phase is evaporated and precipitated with diethylether. The precipitate is filtrated, washed with diethylether and dried. The substance is suspended in 25 ml HCl-solution (1.5M in AcOH) and stirred for 2 hours at room temperature, precipitated with diethylether and ion exchanged in the same way as in example 1. Yield: 63.5percent Patent; KabiVitrum AB; US4797472; (1989); (A1) English View in Reaxys

O HO

S H

(v6)

I–

N H

O O

N+

Rx-ID: 24006318 View in Reaxys 512/630 Yield 70%

Conditions & References 4 : N-[2-[2-[2-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-1,1-dioxido-1 4-benzothiazepin-5-yl]phenoxy]ethoxy]ethoxy]ethoxy]-N,N,N-triethylaminium Iodide Example 4 N-[2-[2-[2-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-1,1-dioxido-1 4-benzothiazepin-5-yl]phenoxy]ethoxy]ethoxy]ethoxy]-N,N,N-triethylaminium Iodide 2-[2-[2-[4-[3,3-Dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-1,1 -dioxido- 1,4-benzothiazepin-5-yl]phenoxy]ethoxy]ethoxy]ethoxy iodide (0.0500 g, 0.0729 mmol), Et3N (0.50 ml, 3.59 mmol) and CH3CN (0.80 ml) were combined in a 25 ml round-bottom flask. The mixture was heated 40° C. After 3 days, the mixture was concentrated in vacuo, and the resulting residue was washed repeatedly with ethyl ether to yield the desired product (0.040 g/70percent). Reverse-phase HPLC: rt=10.9 min, 97percent pure. 1H NMR (CDCl3) δ 0.80 (t, J=6.9 Hz, 3H), 0.86 (t, J=6.3 Hz, 3H), 1.11-1.43 (m, 10H), 1.34 (t, J=6.9 Hz, 9H), 1.78 (m, 1H), 2.15 (m, 1H), 2.80 (s, 6H), 3.24 (qAB, JAB=13.8 Hz, Δν=155.4 Hz, 2H), 3.50 (q, J=7.2 Hz, 6H), 3.71 (br s, 6H), 3.83 (m, 2H), 4.00 (br s, 2H), 4.11 (m, 2H), 5.92 (s, 1H), 5.96 (s, 1H), 6.47 (d, J=9.6 Hz, 1H), 6.89 (d, J=8.7 Hz, 2H), 7.33 (d, J=8.7 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H). LC/MS (ES/M-HI): 659.5. Patent; Tremont, Samuel J.; Koeller, Kevin J.; Neumann, William L.; US2002/183307; (2002); (A1) English View in Reaxys

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N N

HCl N

Rx-ID: 24904590 View in Reaxys 513/630 Yield 70%

Conditions & References 9 : 2-(1H-1,2,4-triazole-1-yl)-4-methyl-quinoline hydrochloride EXAMPLE 9 2-(1H-1,2,4-triazole-1-yl)-4-methyl-quinoline hydrochloride A mixture of 1.78 g of 2-chloro-4-methyl-quinoline, 0.76 g of 1,2,4-triazole and 10 ml of chloro benzene is stirred at 100° C. for 7 hours. The reaction mixture is cooled, the precipitated product is filtered, dissolved in 5 ml of ethanol and precipitated by adding 10 ml of ethyl ether. The precipitated product is filtered. Thus 1.72 g of the desired compound are obtained, yield 70percent. Mp.: 193°-194° C. Patent; Alkaloida Vegyeszeti Gyar; US5104884; (1992); (A1) English View in Reaxys

N-acetopimaricin benzyl ester

Rx-ID: 25060032 View in Reaxys 514/630 Yield 60%

Conditions & References VII : EXAMPLE VII EXAMPLE VII 0.3 g of N-acetopimaricin with E1 cm1percent =110 at 304 nm and 0.2 g of DCCJ are dissolved in 2 ml of freshly distilled benzyl alcohol and allowed to stand over night at room temperature. The residue precipitated with a mixture of ethyl ether:hexane (2:1) is supplied to the column filled with the gel Sephadex LH 20 and submitted to chromatography in the system of chloroform:methanol (5:1). There are obtained 0.2 g of N-acetopimaricin benzyl ester (E1 cm1percent =1000 at 1304 nm), that constitutes 60percent of theoretical yield. Patent; Politechnika Gdanska; US4365058; (1982); (A1) English View in Reaxys

cyclo-(Gly-Orn(Lithocholyl)-Cyc(Ts)-Gly-Gly-)

Rx-ID: 25858207 View in Reaxys 515/630 Yield 56%

Conditions & References 1.N : N. N. Synthesis of cyclo-(Gly-Orn(Lithocholyl)-Cyc(Ts)-Gly-Gly-) To a solution of cyclo-(Gly-Orn-Cyc(Ts)-Gly-Gly-) (1.0 g, 1.9 mmol) in CHCl3 (25 mL) was added lithocholic acid NHS active ester (881 mg, 1.9 mmol) and the resulting mixture was stirred for 16 h thereafter. Addition of ethyl ether (50 mL) produced a solid. Filtration afforded 946 mg (56percent yield) of the product as a tan powder: 1H NMR (CD3OD) δ 0.66 (m, 3H), 0.93 (bs, 6H), 0.94-2.37 (complex m, 48H), 2.43 (s, 3H), 2.80-4.60 (bm, 14H), 7.39 (bs, 2H), 7.80 (bs, 2H); MS (HRFAB) m/z 895.5432 (M+H)+; 895.5367 calculated for C48H75N6O8S. Patent; MetaPhore Pharmaceuticals, Inc.; US2004/57904; (2004); (A1) English View in Reaxys

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O N

N N

Rx-ID: 24145874 View in Reaxys 516/630 Yield 64.8%

Conditions & References 64 : Synthesis of 1-Benzyl-6,7-dimethoxy-4-pyridin-4-ylmethyl-phthalazine (Compound 20) EXAMPLE 64 Synthesis of 1-Benzyl-6,7-dimethoxy-4-pyridin-4-ylmethyl-phthalazine (Compound 20) In anhydrous environment, ZnCl2 (863 mg, 6.33 mmoles) was dissolved in tetrahydrofuran (20 ml), and a 2M solution of benzyl magnesium chloride in tetrahydrofuran (3.2 ml, 2.5 equivalents) was dropped therein. After 30 minutes 1-chloro-6,7-dimethoxy-4-pyridin-4-ylmethyl-phthalazine (800 mg, 2.53 mmoles), obtained as described in example 63, palladium acetate (71 mg, 0.316 mmole) and triphenylphosphine (166 mg, 0.633 mmole) were added and the whole was refluxed. After 1 hour the mixture was poured into a saturated solution of NH4Cl and by adding ethyl acetate a solid precipitated. The whole was evaporated to dryness and the residue taken up in methylene chloride and extracted with concentrated ammonia. The organic phase was dried to yield a residue which was chromatographed (eluent:methylene chloride/2percent methanol, then methylene chloride/5percent methanol). The oily elude was dissolved in methylene chloride and by adding HCl/ethyl ether a precipitate formed which was tritured in ethyl acetate and filtered to give 788 mg of the title product (yield: 64.8percent). 1H-NMR (200 MHz, DMSO) δ (ppm): 8.89-8.06 (m, 4H); 7.96 and 7.86 (2, 2H); 7.54-7.19 (m, 5H); 5.23 and 5.04 (2s, 4H); 4.08 and 4.03 (2s, 6H). Patent; Zambon Group S.p.A.; US6589951; (2003); (B1) English View in Reaxys (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, trifluoroacetic acid salt

Rx-ID: 24217549 View in Reaxys 517/630 Yield

Conditions & References 17 : (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3cephem-4-carboxylate, trifluoroacetic acid salt Example 17 (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4carboxylate, trifluoroacetic acid salt (7R)-7-[(Z)-2-(N-triphenylmethylaminothiazol-4-yl)-2-(triphenylmethoxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, 4-methoxybenzylester(40 mg) was dissolved in 0.1 ml of anisole and 0.9 ml of dichloroacetic acid. The resulting mixture was stirred at room temperature for 3 hours and then precipitated by addition of diethyl ether (100 ml). The precipitate was filtered and subjected to HP-20 reverse phase chromatography to give the title compound. 1H NMR (D2 O) δ3.60 (q, 2H, J=6), 4.60 (q, 2H, J=10), 5.20 (d, 1H, J=4), 5.80 (d, 1H, J=4), 6.90 (s, 1H), and 9.13 (s, 1H). IR (KBr) 997, 1042, 1180, 1349, 1386, 1533, 1615, 1655, and 1768 cm-1. Patent; Microcide Pharmaceuticals, Inc.; US6057312; (2000); (A1) English View in Reaxys 17 : (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3cephem-4-carboxylate, trifluoroacetic acid salt Example 17 (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4carboxylate, trifluoroacetic acid salt (7R)-7-[(Z)-2-(N-triphenylmethylaminothiazol-4-yl)-2-(triphenylmethoxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, 4-methoxybenzyl ester(40 mg) was dissolved in 0.1 ml of anisole and 0.9 ml of dichloroacetic acid.

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The resulting mixture was stirred at room temperature for 3 hours and then precipitated by addition of diethyl ether (100 ml). The precipitate was filtered and subjected to HP-20 reverse phase chromatography to give the title compound. 1H NMR (D2 O) δ 3.60 (q, 2H, J=6), 4.60 (q, 2H, J=10), 5.20 (d, 1H, J=4), 5.80 (d, 1H, J=4), 6.90 (s, 1H), and 9.13 (s, 1H). IR (KBr) 997, 1042, 1180, 1349, 1386, 1533, 1615, 1655, and 1768 cm-1. Patent; Microcide Pharmaceuticals, Inc.; US6066630; (2000); (A1) English View in Reaxys Patent; Microcide Pharmaceuticals, Inc.; US6087355; (2000); (A1) English View in Reaxys Patent; Microcide Pharmaceuticals, Inc.; US5859256; (1999); (A1) English View in Reaxys 17 : (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3cephem-4-carboxylate, trifluoroacetic acid salt Example 17 (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4carboxylate, trifluoroacetic acid salt (7R)-7-[(Z)-2-(N-triphenylmethylaminothiazol-4-yl)-2-(triphenylmethoxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, 4-methoxybenzylester(40 mg) was dissolved in 0.1 ml of anisole and 0.9 ml of dichloroacetic acid. The resulting mixture was stirred at room temperature for 3 hours and then precipitated by addition of diethyl ether (100 ml). The precipitate was filtered and subjected to HP-20 reverse phase chromatography to give the title compound. 1H NMR (D2O) δ 3.60 (q, 2H, J=6), 4.60 (q, 2H, J=10), 5.20 (d, 1H, J=4), 5.80 (d, 1H, J=4), 6.90 (s, 1H), and 9.13 (s, 1H). IR (KBr) 997, 1042, 1180, 1349, 1386, 1533, 1615, 1655, and 1768 cm-1. Patent; Microcide Pharmaceuticals, Inc.; EP1059293; (2000); (A1) English View in Reaxys

S O

Rx-ID: 24989239 View in Reaxys 518/630 Yield 50%

Conditions & References 121 : 1,3,8,9-tetrahydro-1-methylthio-2H-benz[e]indole-2,6(7H)-dione EXAMPLE 121 1,3,8,9-tetrahydro-1-methylthio-2H-benz[e]indole-2,6(7H)-dione A solution of ethyl (methyl thio) acetate (6 g) in methylene chloride (20 ml) was added dropwise to a solution of chlorine (2 ml) in methylene chloride (100 ml) at -78° C. To this colorless solution was added a solution of 6-amino-1-tetralone (6.4 g) in methylene chloride (170 ml) and triethyl amine (5.6 ml) dropwise over 30 minutes. After stirring the reaction mixture at -70° C. for 5 hours a solution of triethyl amine (8 ml) in methylene chloride (20 ml) was added and the reaction was warmed to room temperature and quenched with water. The aqueous layer was extracted with methylene chloride and the organic layer was stirred with 2.5N hydrochloric acid (100 ml) overnight. The organic layer was separated, dried and evaporated to afford the desired compound after triturating with diethylether in 50percent yield. Patent; Abbott Laboratories; US4634705; (1987); (A1) English View in Reaxys

H--D--Arg--Gly--Arg--pNA.3HCl

Rx-ID: 25147483 View in Reaxys 519/630 Yield 38%

Conditions & References 3 : H--D--Arg--Gly--Arg--pNA.3HCl EXAMPLE 3 H--D--Arg--Gly--Arg--pNA.3HCl

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Molecular weight=616.96 22 ml TFA is added to 12 mmol Nα --Boc--D--Arg--Gly--Arg--pNA.2HCl (prepared according to example 2) dissolved in 22 ml methylenechloride. The mixture is stirred for 30 minutes at room temperature and precipitated with diethylether thereafter. The product is ion exchanged and purified in the same way as in example 1. Yield: 38percent Patent; KabiVitrum AB; US4797472; (1989); (A1) English View in Reaxys O NH

O O

Rx-ID: 25414448 View in Reaxys 520/630 Yield 50 %

Conditions & References 8 : EXAMPLE 8 EXAMPLE 8 Preparation of (S)-3-(4-methoxybenzoylamino)-ε-caprolactam (ST 734). CDl (1.96 g; 12 mmoles) was added under stirring to 4-methoxybenzoic acid (1.52 g; 10 mmoles) in CH2Cl2(50 mL) and after 30 minutes (S)-3-amino-ε--caprolactam (1.28 g, 10 mmoles) was added. The reaction mixture was kept under stirring at room temperature for 24 hours, the solvent was evaporated and the residue chromatographed on silica gel using EtOAc-MeOH as eluant (9:1). The solid thus obtained was taken up with CH2Cl2 e precipitated with Et2O obtaining 1.3 g of product. Yield = 50 percent M.P. = 170-172° C [α] [25/D ] =+ 42.2°MeOH (C=1) TLC on silica gel; eluant EtOAc RF= 0.3 Elementary analysis for C1 4H1 8N2O3 1H-NMR(CDCl3):δ7.82(d,2H,aromatic),7.58(br d,1H,-CH NH CO-), 6.93(d, 2H,aromatic),6.58(br t,1H,-CH2 NH CO-),4.76-466(m,1H,-CHNCO-), 3.85(s,3H-O CH 3),3.42-3.22(m,2H, CH 2NCO-), 2.3-2.18(m,1H,-CH H CHN-),2.1-1.82(m,3H,- CH 2CH2C H HCHN-),1.64-1.35(m,2H,- CH 2CH2CHNCO-). HPLC μBondapack C1 8 Length = 300 mm Inner Diameter = 3.9 mm Size = 10 μm Eluant = KH2PO4 0.05/CH3CN (60:40) Flow rate = 1 mL/min. Retention time = 4.9 min. Patent; Sigma-Tau Industrie, Farmaceutiche Riunite S.p.A.; EP462949; (1991); (A1) English View in Reaxys

O O

Rx-ID: 24367010 View in Reaxys 521/630 Yield 28%

Conditions & References 3.b : 3b. 3b. Synthesis of 4-(3-Chloro-phenyl)-1-methyl-6-(1-trityl-1H-imidazol-4-ylmethoxy)-1H-quinolin-2-one STR46 To dichloromethane was added (1-trityl-1H-imidazol-4-yl)-methanol (0.7 g, 2.05 mmol), 4-(3-chlorophenyl)-6-hydroxy-1-methyl-1H-quinolin-2-one (0.56 g, 1.96 mmol) and triphenylphosphine (0.56 g, 2.14 mmol) giving a suspension. To this was added tetrahydrofuran, 25 mL. A solution of diethyl azodicarbozylate (0.374 g, 2.14 mmol) in 20 mL tetrahydrofuran was added over 3 minutes. The mixture was stirred overnight at 25° C.

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The mixture was evaporated in vacuo, and the residue was taken up into ethyl ether and water, giving a suspended solid. The mixture was filtered and the solid dissolved in methylene dichloride. The solution was washed with brine, dried over anhydrous magnesium sulfate, filtered, and precipitated by addition of ethyl ether. The resulting solid was filtered and dried giving a solid, 0.339 g. The solid was chromatographed on 25 g silica gel which was eluted with chloroform. The product was recovered as a solid, 0.33 g, 28percent yield, NMR was consistent with structure. Patent; Warner-Lambert Company; US6143766; (2000); (A1) English View in Reaxys

O O

F F

Rx-ID: 25002592 View in Reaxys 522/630 Yield

Conditions & References 14 : 1-[2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepin-1-yl)methoxy]ethyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine EXAMPLE 14 1-[2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepin-1-yl)methoxy]ethyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine A mixture of 0.10 g (1.50 mmoles) of 2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepine-1-yl)methoxy]ethyl-4-nitrobenzenesulfonate, 0.37 g (1.50 mmoles) of 4-hydroxy-4-(3-trifluoromethylphenyl)piperidine, 0.21 ml (1.50 mmoles of triethylamine and 30 ml of tetrahydrofuran is stirred at room temperature for 3 days, at 50° for 1 day, and again at room temperature for 2 days, after which the tetrahydrofuran is removed in vacuo. The reaction mixture is extracted with methylene chloride and aqueous sodium bicarbonate. The organic layer is filtered through sodium sulfate and taken to dryness and chromatographed on silica gel with 2percent methanol:0.5percent ammonium hydroxide:methylene chloride as eluent to give 0.46 g (60percent) of the titled product. The hydrochloride salt is prepared with hydrochloric acid/ethyl ether, m.p. 156°-159°. Analysis: Calc'd. for C27 H34 F3 NO5.HCl.1/2H2 O C, 58.43; H, 6.54; N, 2.52; Cl, 6.34. Found: C, 58.60; H, 6.49; N, 2.85; Cl, 7.08. Patent; The Upjohn Company; US4247553; (1981); (A1) English View in Reaxys 14 : 1-[2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepin-1-yl)methoxy]ethyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine EXAMPLE 14 1-[2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepin-1-yl)methoxy]ethyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine A mixture of 0.10 g (1.50 mmoles) of 2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepine-1-yl)methoxy]ethyl 4-nitrobenzenesulfonate, 0.37 g (1.50 mmoles) of 4-hydroxy-4-(3-trifluoromethylphenyl)piperidine, 0.21 ml (1.50 mmoles) of triethylamine and 30 ml of tetrahydrofuran is stirred at room temperature for 3 days, at 50° for 1 day, and again at room temperature for 2 days, after which the tetrahydrofuran is removed in vacuo. The reaction mixture is extracted with methylene chloride and aqueous sodium bicarbonate. The organic layer is filtered through sodium sulfate and taken to dryness and chromatographed on silica gel with 2percent methanol:0.5percent ammonium hydroxide:methylene chloride as eluent to give 0.46 g (60percent) of the titled product. The hydrochloride salt is prepared with hydrochloric acid/ethyl ether, m.p. 156°-159°.

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Analysis: Calc'd. for C27 H34 F3 NO5.HCl.1/2H2 O: C, 58.43; H, 6.54; N, 2.52; Cl, 6.34. Found: C, 58.60; H, 6.49; N, 2.85; Cl, 7.08. Patent; The Upjohn Company; US4153612; (1979); (A1) English View in Reaxys 8 : 1-[2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepin-1-yl)methoxy]ethyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine EXAMPLE 8 1-[2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepin-1-yl)methoxy]ethyl]-4-hydroxy-4-(3-trifluoromethylphenyl)piperidine A mixture of 0.10 g (1.50 mmoles) of 2-[(1,3,4,5-tetrahydro-7,8-dimethoxy-2-benzoxepine-1-yl)methoxy]ethyl 4-nitrobenzenesulfonate, 0.37 g (1.50 mmoles) of 4-hydroxy-4-(3-trifluoromethylphenyl)piperidine, 0.21 ml (1.50 mmoles) of triethylamine and 30 ml of tetrahydrofuran is stirred at room temperature for 3 days, at 50° for 1 day, and again at room temperature for 2 days, after which the tetrahydrofuran is removed in vacuo. The reaction mixture is extracted with methylene chloride and aqueous sodium bicarbonate. The organic layer is filtered through sodium sulfate and taken to dryness and chromatographed on silica gel with 2percent methanol:0.5percent ammonium hydroxide:methylene chloride as eluent to give 0.46 g (60percent) of the titled product. The hydrochloride salt is prepared with hydrogen chloride/ethyl ether; m.p. 156°-159°. Analysis: Calc'd. for C27 H34 F3 NO5.HCl.1/2H2 O C, 58.43; H, 6.54; N, 2.52; Cl, 6.34. Found: C, 58.60; H, 6.49; N, 2.85; Cl, 7.08. Patent; The Upjohn Company; US4166062; (1979); (A1) English View in Reaxys H-Cys-βAla-D-Arg-D-Arg-D-Met-D-Lys-D-Trp-D-Lys-D-LysNH2

Rx-ID: 24075432 View in Reaxys 523/630 Yield

Conditions & References 7 : H-Cys-βAla-D-Arg-D-Arg-D-Met-D-Lys-D-Trp-D-Lys-D-Lys-NH2 Example 7 H-Cys-βAla-D-Arg-D-Arg-D-Met-D-Lys-D-Trp-D-Lys-D-Lys-NH2 Starting from Rink Amide AM resin (0.69 mmol/g, Novabiochem). H-Cys(Trt)-βAla-D-Arg(Pmc)-D-Arg(Pmc)-D-MetD-Lys(Boc)-D-Trp-D-Lys(Boc)-D-Lys(Boc)-resin was assembled. After deprotection (1.5 h), the crude peptide was obtained by precipitation from Et2O, centrifugation/decantation, and drying. Aliquots (total 237 mg) were purified by preparative RP-HPLC (8-18percent MeCN gradient) to afford the pure title compound (66 mg). Anal. RP-HPLC: tR=12.9 min (9-19percent MeCN gradient, purity>99percent. λ=214 nm). DE MALDI-TOF MS: [M+H]-=1207.2 (C52H92N20O9S2=1205.55). Patent; Cyclacel Limited; US2002/98236; (2002); (A1) English View in Reaxys 15 : H-Cys-βAla-D-Arg-D-Arg-D-Met-D-Lys-D-Trp-D-Lys-D-Lys-NH2 (SEQ ID No. 19) Example 15 H-Cys-βAla-D-Arg-D-Arg-D-Met-D-Lys-D-Trp-D-Lys-D-Lys-NH2 (SEQ ID No. 19) Starting from Rink Amide AM resin (0.69 mmol/g, Novabiochem), H-Cys(Trt)-βAla-D-Arg(Pmc)-D-Arg(Pmc)-D-MetD-Lys(Boc)-D-Trp-D-Lys(Boc)-D-Lys(Boc)-resin (SEQ ID No. 19) was assembled. After deprotection (1.5 h), the crude peptide was obtained by precipitation from Et2O, centrifugation/decantation, and drying. Aliquots (total 237 mg) were purified by preparative RP-HPLC (8-18percent MeCN gradient) to afford the pure title compound (66 mg). Anal. RP-HPLC: tR=12.9 min (9-19percent MeCN gradient, purity>99percent, λ=214 nm). DE MALDI-TOF MS: [M+H]+=1207.2 (C52H92N20O9S2=1205.55). Patent; Cyclacel Limited; US6472507; (2002); (B1) English View in Reaxys

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N H N

Cl HCl

Rx-ID: 24075443 View in Reaxys 524/630 Yield 22%

Conditions & References 111 : {1-[1-(3,4-Dichloro-phenyl)-1H-imidazol-4-yl-methyl]-1H-imidazol-2-yl}-ethyl-amine Hydrochloride (1:2) EXAMPLE 111 {1-[1-(3,4-Dichloro-phenyl)-1H-imidazol-4-yl-methyl]-1H-imidazol-2-yl}-ethyl-amine Hydrochloride (1:2) N-{1-[1-(3,4-Dichloro-phenyl)-1H-imidazol-4-ylmethyl]-1H-imidazol-2-yl}-acetamide (0.30 g, 0.86 mmol) was treated with 1M BH3 THF complex (1.6 ml) and refluxed for 2 h. The mixture was cooled to 5° C. and MeOH (5 ml) was added slowly. After evaporation of all volatiles the residue was taken up in 2N HCl solution (3 ml) and refluxed for 20 min. The mixture was cooled and 2N NaOH solution (3 ml) was added. After extraction with AcOEt (50 ml), the organic phase was dried (Na2SO4) and evaporated to dryness. Purification by chromatography [silica, elution with gradient CH2Cl2 to 50percent (CH2Cl2/MeOH/aq. NH4OH=90:10:1)] gave the free base of the title compound. After treatment with a solution of HCl in MeOH followed by addition of Et2O the title compound was isolated as an off-white crystalline material (0.062 g, 22percent). Mp.>250° C. (MeOH/Et2O), MS: m/e=336 (M+H'). Patent; Alanine, Alexander; Buettelmann, Bernd; Heitz Neidhart, Marie-Paule; Jaeschke, Georg; Pinard, Emmanuel; Wyler, Rene; US2002/151715; (2002); (A1) English View in Reaxys O O N+ Cl –

N O

Cl Cl

Rx-ID: 24520409 View in Reaxys 525/630 Yield

Conditions & References 13.7 : Step 7 Step 7 0.5 g of the product prepared above and 0.25 g of 4-phenylquinuclidine are dissolved in 1 ml of dimethylformamide and the reaction mixture is heated at 80° C. for two hours. The reaction mixture is poured into water and then successively extracted with AcOET, washed with water, with a saturated solution of NaCl, concentrated under vacuum and the residue is chromatographed on silica gel using CH2 Cl2/ CH3 OH (100/5 v/v) as the eluent. The pure fractions are concentrated under vacuum, the residue is taken up in CH2 Cl2 and precipitated by adding ethyl ether to give 0.45 g of 1-[3-(3,4-dichlorophenyl)-4-(N-(2-acetoxyethyl)-3-isopropoxyphenylacetylamino)butyl]-1azoniabicyclo[2.2.2.]octane chloride (Compound 13). M.p.=90°-92° C. Patent; Sanofi; US5554763; (1996); (A1) English View in Reaxys Patent; Sanofi; US5583134; (1996); (A1) English View in Reaxys 13.7 : Step 7 Step 7 0.5 g of the product prepared above and 0.25 g of 4-phenylquinuclidine are dissolved in 1 ml of dimethylformamide and the reaction mixture is heated at 80° C. for two hours. The reaction mixture is poured into water and then successively extracted with AcOET, washed with water, with a saturated solution of NaCl, concentrated under vacuum and the residue is chromatographed on silica gel using CH2 Cl2 /CH3 OH (100/5 v/v) as the eluent. The pure fractions are concentrated under vacuum, the residue is taken up in CH2 Cl2 and precipitated by adding ethyl ether to give 0.45 g of 1-[3-(3,4-dichlorophenyl)-4-(N-(2-acetoxyethyl)-3-isopropoxyphenylacetylamino)butyl]-1azoniabicyclo[2.2.2.]octane chloride (Compound 13). M.p. =90°-92° C.

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Patent; Sanofi; US5679693; (1997); (A1) English View in Reaxys

Na +

N N O

–O

O O

Rx-ID: 24595323 View in Reaxys 526/630 Yield 23%

Conditions & References 1 : Sodium 7-(3,4,5-triphenyl-2-oxo-2,3-dihydroimidazol-1-yl)-heptane-sulphonate A solution of 1,4,5-triphenyl-3-(7-bromoheptyl)imidazol-2-one (2.0 g) in ethanol (10 ml) was refluxed with a solution of sodium sulphite (0.55 g) in water (5 ml) for 20 hours. More sodium sulphite (0.2 g) was added and refluxing continued for a further 20 hours. The mixture was evaporated to dryness, boiled in ethanol, filtered hot and evaporated to an oil. This was taken up in a small volume of ethanol, excess diethyl ether added and the precipitated solid filtered off and chromatographed on silica gel (dichloro-methane/methanol 5:1). The resulting oil in methanol/water 1:1 was passed down an Amberlyst 15 ion exchange resin (Na form) and evaporated to a solid. This was taken up in ethanol and precipitated with diethyl ether giving sodium 7-(3,4,5-triphenyl-2-oxo-2,3-dihydroimidazol-1-yl)heptane-sulphonate (0.49 g), 23percent) as a white solid, m.p. 160° C. Found: C, 63.47; H, 5.69; N, 5.04; S, 5.63percent; C28 H29 N2 NaO4 S+3.5percent water; Requires: C, 63.31; H, 5.89; N, 5.28; S, 6.04percent Patent; SmithKline Beecham Corporation; The Johns Hopkins University; US5648373; (1997); (A1) English View in Reaxys

D-glucaro-δ-lactam ethyl ester

Rx-ID: 24822627 View in Reaxys 527/630 Yield

Conditions & References R.3 : REFERENCE EXAMPLE 3 REFERENCE EXAMPLE 3 To a solution of 1.8 g D-glucaro-δ-lactam in 20 ml of N,N-dimethylformamide were added 2.5 g of K2 CO3 and 3 g of ethyl iodide and the reaction was conducted at 50° C. with stirring for 10 hours. The insolubles were filtered off and the filtrate was concentrated. The residue was extracted with 50 ml of warm ethanol and the extract was concentrated to about 10 ml and, then, caused to precipitate from ethyl ether. The procedure gave 1.4 g of D-glucaro-δ-lactam ethyl ester. Thin-layer chromatography on silica gel (chloroform/methanol=4/1): Rf 0.17 Patent; Meiji Seika Kaisha, Ltd.; US4954510; (1990); (A1) English View in Reaxys REFERENCE EAMPLE 3 REFERENCE EAMPLE 3 To a solution of 1.8 g D-glucaro-δ-lactam in 20 ml of N,N-dimethylformamide were added 2.5 g of K2CO3 and 3 g of ethyl iodide and the reaction was conducted at 50°C with stirring for 10 hours. The insolubles were filtered off and the filtrate was concentrated. The residue was extracted with 50 ml of warm ethanol and the extract was concentrated to about 10 ml and, then, caused to precipitate from ethyl ether. The procedure gave 1.4 g of D-glucaro-δ-lactam ethyl ester. Thin-layer chromatography on silica gel (chloroform/methanol = 4/1): Rf 0.17 Patent; MEIJI SEIKA KAISHA LTD.; EP322822; (1989); (A2) English View in Reaxys

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Rx-ID: 24006122 View in Reaxys 528/630 Yield

Conditions & References 12.b : a b) (R)-1-(2-tert-Butoxycarbonylamino-1-methyl-ethyl)-6-trifluoromethyl-1H-indole-2-carboxylic acid ethyl ester: Sodium hydride (0.75 g, 17 mmol) was suspended in N,N-dimethylformamide (15 mL) and a solution of 6-trifluoromethyl-1H-indole-2-carboxylic acid ethyl ester (3.6 g, 14 mmol) in N,N-dimethylformamide (15 mL) was added with cooling at 50° C. After 1 h (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester (4.0 g, 17 mmol) was added and the solution was allowed to reach room temperature over the weekend. The solution was partitioned between ice water (600 mL) and diethylether (2-*250 mL). The organic layer was washed with ice water and brine, dried (MgSO4), and evaporated. Chromatography on silica gel with n-hexane/diethylether (4:1) yielded the title product as yellow oil (5.1 g, 88percent). ISP-MS: m/e=415.3 (M+H+), αD 20=-29.6 Patent; Bentley, Jonathan M.; Hebeisen, Paul; Muller, Marc; Richter, Hans; Roever, Stephan; US2002/35110; (2002); (A1) English View in Reaxys 9 : 3'-N-(Gylcyl-L-leucyl-L-phenylalanyl) doxorubicin (5a) STR15 EXAMPLE 9 3'-N-(Gylcyl-L-leucyl-L-phenylalanyl) doxorubicin (5a) STR15 Doxorubicin hydrochloride (2.9 g, 5 mmol) dissolved in anhydrous dimethylformamide (50 ml) and triethylamine (0.5 ml), was reacted with N-trityl-Phenylalanylleucylglycyl p-nitrophenylester (9a: 3.5 g, 5 mmol) prepared as described in Example 7. The reaction mixture was kept overnight at room temperature, then precipitated with a mixture 1:1 of ethyl ether and n-hexane. The solid was purifyied through silica gel column eluding with a mixture of methylene chloride and methanol (98:2 by volume) to give N-protected peptidyl doxorubicin 10a (4.6 g), TLC on Kieselgel plate F254 (Merck), eluding system methylene chloride/methanol (95:5 by volume) Rf =0.35. FD-MS: m/z 1103 [M+H]+. Patent; Farmitalia Carlo Erba S.r.l; US5571785; (1996); (A1) English View in Reaxys

F OH O

E OH

O O

O N

Rx-ID: 24461540 View in Reaxys 529/630 Yield

Conditions & References 132 : 2-[[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate EXAMPLE 132 2-[[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate A mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethylamine (2.0 gm, 7.6 mmol), K2 CO3 (1.38 gm, 10 mmol) and bromoethyl acetate (1.40 gm, 8.3 mmol) in acetonitrile (50 ml) was heated at reflux for 4 hr. At the end, the insolubles were filtered off and rinsed with DCM. The solvent was evaporated down. The crude mixture was purified by flash chromatography over a silica gel column (Sorbsil C-30, 30 gm; eluted with 2percent CH3 OH in DCM, 800 ml). The oil (1.15 gm) thus obtained was treated with a solution of fumaric acid (358 mg) in ethanol. Crystallization was induced by adding drops of ethyl ether, yield: 1.09 gm, m.p.=116°-118° C. Patent; Hoechst-Roussel Pharmaceuticals, Inc.; US5364866; (1994); (A1) English View in Reaxys 132 : 2-[[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate EXAMPLE 132 2-[[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amino]ethyl acetate fumarate

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A mixture of 2-[4-[(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]amine (2.0 g, 7.6 mmol), K2 CO3 (1.38 g, 10 mmol) and bromoethyl acetate (1.40 g, 8.3 mmol) in acetonitrile (50 ml) was heated at reflux for 4 hours. At the end, the insolubles were filtered off and rinsed with DCM. The solvent was evaporated down. The crude mixture was purified by flash chromatography over a silica gel column (Sorbsil C-30, 30 g; eluted with 2percent CH3 OH in DCM, 800 ml). The oil (1.15 g) thus obtained was treated with a solution of fumaric acid (358 mg) in ethanol. Crystallization was induced by adding drops of ethyl ether, yield: 1.09 g, m.p.=116-118° C. ANALYSIS: Calculated for C18 H24 FN3 O3 *C4 H4 O4: 56.77percent C 6.06percent H 9.03percent N Found: 56.32percent C 5.97percent H 8.94percent N Patent; Hoechst Marion Roussel, Inc.; US5776963; (1998); (A1) English View in Reaxys

N O

Rx-ID: 24991463 View in Reaxys 530/630 Yield

Conditions & References EXAMPLES 9 TO 14 EXAMPLES 9 TO 14 The different compounds from 9 to 14 are synthesised by the following general process: A solution containing compound No. 5 (0.01 mol), triethylamine (1.4 cc) and ethyl ether (20 cc) is prepared. Patent; Rhone-Poulenc Agrochimie; US4690708; (1987); (A1) English View in Reaxys 47 : EXAMPLE 47 EXAMPLE 47 N-Chloromethylcarbonyl-3-azabicyclo[3.2.2]nonane required as a starting material in this example was prepared substantially as described in copending Application Ser. No. 278,997, filed May 8, 1963, A mixture of 125 grams (1.0 mole) of amine, 101.3 grams (1.0 mole) of triethylamine, and 1500 ml. of ethyl ether was prepared and 113 grams (1.0 mole) of chloroacetyl chloride added dropwise over a period of 15 minutes. The temperature during the addition was maintained at 25°-30° C. by means of an ice-bath. Stirring was continued at this same temperature for 24 hours, a liter of water added, and stirring continued for an additional 15 minutes. The ether layer was washed with water until the washings were neutral to litmus and dried over sodium sulfate. The ether was removed in vacuo at a maximum temperature of 30° C./10-12 mm. and the resulting solid air-dried at 25°-30° C. Patent; Monsanto Company; US4013638; (1977); (A1) English View in Reaxys

H N

OH S N

Rx-ID: 25283368 View in Reaxys 531/630 Yield

Conditions & References 1.D : Step D: To a solution of 0.065 g. of benzyl 6-azido-6-methoxypenicillanate in 20 ml. of acetic anhydride is added 0.065 g. of platinum oxide, and the mixture is hydrogenated at atmospheric pressure for 18 hours. The resulting solution is concentrated under reduced pressure at a temperature below 40° C. to remove the acetic anhydride. The resulting residue is taken up in a mixture of equal volumes of methylene chloride and ethyl ether and filtered through diatomaceous earth to remove the catalyst.

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The filtrate and washings are evaporated under reduced pressure to afford 0.066 g. of benzyl 6β-acetamido-6-methoxypenicillanate. The crude product is purified by thin layer chromatography to yield 0.03 g. of pure product. Rf of 0.52 (2percent CH3 OH/CHCl3); IR: 5.59 μ (β-lactam) and 5.71μ (ester). NMR: 2.63 tau (s), (phenyl); 4.4 tau (s), (5H); 4.80 tau (s), (CH2 C6 H5); 5.52 tau (s), (3H); 6.53 tau (s), (OCH3); 7.9 tau (s), STR10 8.45 tau (s) and 8.60 tau (s), (gem CH3). Patent; Merck and Co., Inc.; US4071529; (1978); (A1) English View in Reaxys 1.D : Step D To a solution of 0.065 g. of benzyl 6-azido-6-methoxypenicillanate in 20 ml. of acetic anhydride is added 0.065 g. of platinum oxide, and the mixture is hydrogenated at atmospheric pressure for 18 hours. The resulting solution is concentrated under reduced pressure at a temperature below 40° C. to remove the acetic anhydride. The resulting residue is taken up in a mixture of equal volumes of methylene chloride and ethyl ether and filtered through diatomaceous earth to remove the catalyst. The filtrate and washings are evaporated under reduced pressure to afford 0.066 g. of benzyl 6β-acetamido-6-methoxypenicillanate. The crude product is purified by thin layer chromatography to yield 0.03 g. of pure product. Rf of 0.52 (2percent CH3 OH/CHCl3); IR: 5.59μ (β-lactam) and 5.71μ (ester). NMR: 2.63 tau (s), (phenyl); 4.4 tau (s), (5H); 4.80 tau (s) (CH2 C6 H5); 5.52 tau (s), (3H); 6.53 tau (s), (OCH3); 7.9 tau (s), STR11 8.45 tau (s) and 8.60 tau (s), (gem CH3). Patent; Merck and Co., Inc.; US4035359; (1977); (A1) English View in Reaxys 1,3,3,5,7,7-hexamethyl-2,6-di[3-(1,1,3-trimethyl-2,3-dihydro-1H-2-indenyliden)-1-propenyl]-3,7-dihydropyrrolo[2,3-f]indolediium-di(4-methyl-1-benzenesulfonate)

Rx-ID: 10640606 View in Reaxys 532/630 Yield

Conditions & References

180 mg (62%)

4 : EXAMPLE 4 EXAMPLE 4 1,3,3,5,7,7-hexamethyl-2,6-di[3-(1,1,3-trimethyl-2,3-dihydro-1H-2-indenyliden)-1-propenyl]-3,7-dihydropyrrolo[2,3f]indolediium-di(4-methyl-1-benzenesulfonate) (7) was synthesised according to (Mihajlenko F. A, Boguslavskaya A. N, Kiprianov A. I.; Khimiya Geterotsykl. Soed. (in Russ), 1971; No 5, p. 618-620). 150 m g (0.75 mmol) of 2-(1,1,3-trimethyl-2,3-dihydro-1H-2-indenyliden) acetaldehyde 4d (H. Fritz, Chemische Berichte; 1959, 92 (8), 1809-17); was dissolved in 5 ml of acetic anhydride, and 182 mg (0.34 mmol) of 1,2,3,3,5,6,7,7octamethyl-3,7-dihydropyrrolo[2,3-f]indoledinium di(4-methyl-1-benzenesulfonate) 3b was added. The mixture was refluxed for 1 hour. After cooling the solvent was removed under reduced pressure by a rotary evaporator. The residue was treated by hexane, filtered off and washed with hexane and Et2O. Solid was redissolved in a minimum volume of nitrometan and precipitated with Et2O. Yield 180 mg (62percent). UV: λmax (abs) 658 nm (CHCl3), λmax (abs) 644 nm (MeOH), λmax (abs) 645 nm (6 mg/ml BSA), λmax (fl) 677 nm (CHCl3), λmax (fl) 664 nm (MeOH), λmax (fl) 668 nm (6 mg/ml BSA); Q.Y. 10.4percent; Q.Y.BSA 6.6percent; δH (200 MHz, DMSO-d6) 8.31 (2H, t, 13.4 Hz, CH), 7.85 (2H, s, bispyrrolenin arom H), 7.65 (2H, d, arom H), 7.53-7.39 (4H, Tos and 4H indolenine H), 7.38-7.25 (2H, m, arom indolenine H), 7.11 (4H, d, 7.8 Hz, Tos H), 6.45 (4H, d, 13.4 C), 3.7 (6H, s, bispyrrolenin NCH3), 3.66 (6H, s, indolenine NCH3), 2.28 (6H, s, Tos CH3), 1.73 (12H, s, bispyrrolenin CH3) 1.7 (12H, s, indolenine CH3). FAB-MS (GI) m/z 621 (Cat-CH3)+, 635 (Cat-H)+, 636 (Cat+++e-)+, 807 (Cat+An)+. Patent; Terpetschnig, Ewald A.; US2007/281363; (2007); (A1) English View in Reaxys

di-peptide Fmoc-6-aminohexanoic acid-GluOH

Rx-ID: 23858881 View in Reaxys 533/630

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Yield

Conditions & References 2.a : Preparation of the Copolymer Backbone Fmoc-6-aminohexanoyl-glutamic Acid and O,O'-bis(2-aminoethyl)poly(ethylene Glycol) 6000 (Diamino-PEG-6000; Fluka) or O,O'-bis(2-aminoethyl)poly(ethylene glycol) 3400 (Diamino-PEG-3400; Fluka) Di-t-butyl-protected derivative (5) was dissolved in 30 ml dichloromethane/trifluoroacetic acid 2:1 and stirred for one hour at room temperature. Upon completeness of reaction (assessed by reverse phase-HPLC), the solvent was reduced to approximately 5percent of the initial volume. Product (6) was yielded upon precipitation from diethyl ether. Patent; Plank, Christian; Stemberger, Axel; Scherer, Franz; US2003/26840; (2003); (A1) English View in Reaxys 7-Ethyl-10-hydroxy-20-O-(leucyl-glycyl)camptothecin trifluoroacetate

Rx-ID: 23858882 View in Reaxys 534/630 Yield

Conditions & References 2 : 7-Ethyl-10-hydroxy-20-O-(leucyl-glycyl)-camptothecin trifluoroacetate (16') Compound (16) was dissolved in trifluoroacetic acid (50 ml of 95percent aqueous solution) and after one hour the solvent was removed under reduced pressure to give the title compound ((16'), yield 3 g) which was collected with ethyl ether in the form of trifluoroacetate salt derivative. Patent; Suarato, Antonio; Angelucci, Francesco; Caruso, Michele; Scolaro, Alessandro; Volpi, Daniele; Zamai, Moreno; US2003/195152; (2003); (A1) English View in Reaxys

6-desoxo-naloxone

Rx-ID: 23936564 View in Reaxys 535/630 Yield

Conditions & References 3 : Synthesis of MPEG (2000 Da)-6-desoxo-naloxone Example 3 Synthesis of MPEG (2000 Da)-6-desoxo-naloxone To a mixture of 6-amino-6-desoxonaloxone.2HCl (0.6 g) (from Step A of Example 1) and mPEG (2000 Da)-propionaldehyde (6.0 g) dissolved in 0.1 M phosphate buffer pH 6.5 was added phosphate buffer solution (pH 6.5, 5 ml) of NaCNBH3. The resulting solution was stirred at room temperature under argon overnight. The reaction mixture was diluted to 500 ml, saturated with NaCl and extracted with dichloromethane. The extracted dichloromethane was dried with Na2SO4, evaporated and precipitated with ethyl ether. The product was dried under vacuum overnight. Yield: 5.63 g GPC: ~25percent of conjugates. Patent; Shearwater Corporation; US2003/124086; (2003); (A1) English View in Reaxys 2-[[(3,8-diaza-8-benzyl-1-oxaspiro[4.3.0]decan-2-yl)methyl](benzyloxycarbonyl)amino]acetic acid

Rx-ID: 23936567 View in Reaxys 536/630 Yield

Conditions & References Synthesis of 2-[[(3,8-diaza-8-benzyl-1-oxaspiro[4.3.0]decan-2-yl)methyl](benzyloxycarbonyl)amino]acetic acid Synthesis of 2-[[(3,8-diaza-8-benzyl-1-oxaspiro[4.3.0]decan-2-yl)methyl](benzyloxycarbonyl)amino]acetic acid To a solution of the compound obtained in Step 2 (1.35 g) in methanol (25 ml), was added a solution of lithium hydroxide monohydrate (0.24 g) in water (10 ml) under cooling with ice. The mixture was stirred under cooling with ice for 10 minutes and at room temperature for 40 minutes. The reaction mixture was concentrated under reduced pressure and to the resulting residue was added water, followed by extraction with ethyl acetate. The aqueous layer was adjusted to pH 2 with 6N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain a compound.

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To a solution of this compound (1.21 g) in methylene chloride (40 ml) were added toluene (40 ml), 4-(aminomethyl)-1-benzyl-4-hydroxypiperidine (1.06 g) and magnesium sulfate (2.90 g) and the mixture was stirred overnight at room temperature. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The resulting residue was solidified by addition of diethyl ether and thereafter the solid content was collected by filtration and dried in vacuum to thereby obtain the title compound (2.05 g). NMR spectrum (*DMSO-d6,100° C.) δppm: 7.39-7.15(10H,m), 5.15-4.98(2H,m),4.62-4.57(1H,m),4.13-3.91(2H,m),3.67-3.25(4H,m),2.88-2.60 (2H,m), 2.56-2.26(4H,m),1.65-1.33(4H,m) Patent; Nishida, Hidemitsu; Saitoh, Fumihiko; Harada, Kousuke; Shiromizu, Ikuya; Mukaihira, Takafumi; US2003/45520; (2003); (A1) English View in Reaxys (+-)-7-[[[2-(4-Azabenzimidazoyl)methyl]methylamino]carbonyl]-4-isopropyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2acetic acid

Rx-ID: 24006319 View in Reaxys 537/630 Yield

Conditions & References 19.b : b b (+-)-7-[[[2-(4-Azabenzimidazoyl)methyl]methylamino]carbonyl]-4-isopropyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetic acid 1.0 N NaOH (1.5 mL, 1.5 mmol) was added to a solution of methyl (+-)-7-[[[2-(4-azabenzimidazolyl)methyl]methylamino]carbonyl]-4-isopropyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate (226.2 mg, 0.49 mmol) in MeOH (5 mL) and H2O (5 mL) at RT. After 24 h, the reaction was neutralized with 1.0 N HCl and the solvents were evaporated under vacuum. ODS chromatography (0.1percent TFA/H2O, followed by 20percent CH3CN/H2O-0percent TFA), concentration, and reconcentration from toluene left a residue, which was redissolved in H2O. Lyophilization gave impure title compound (181.9 mg) as a white powder, which was repurified by ODS chromatography (10percent CH3CN/H2O-0.1percent TFA, followed by 20percent CH3CN/H2O-0.1percent TFA). Concentration and reconcentration from toluene left a residue, which was dissolved in MeOH and precipitated with Et2O. The precipitate was collected on a sintered glass funnel and dried in a vacuum desiccator to afford the title compound (65.5 mg). Patent; SmithKline Beecham Corporation; US2002/32187; (2002); (A1) English View in Reaxys H-Cys-Arg-Arg-Met-Lys-Trp-Lys-Lys-CysNH2

Rx-ID: 24075429 View in Reaxys 538/630 Yield

Conditions & References 12 : H-Cys-Arg-Arg-Met-Lys-Trp-Lys-Lys-Cys-NH2 Example 12 H-Cys-Arg-Arg-Met-Lys-Trp-Lys-Lys-Cys-NH2 Starting from Rink Amide AM resin (0.69 mmol/g, Novabiochem), H-Cys(Trt)-Arg(Pmc)-Arg(Pmc)-Met-Lys(Boc)-TrpLys(Boc)-Lys(Boc)-Cys(Trt)-resin was assembled. After deprotection (1.5 h), the crude peptide was obtained by precipitation from Et2O, centrifugation/decantation, and drying. Aliquots (total 258 mg) were purified by preparative RP-HPLC (9-19percent MeCN gradient) to afford the pure title compound (132.4 mg). Anal. RP-HPLC: tR=20.3 min (8-18percent MeCN gradient, purity>99percent, λ=214 nm). DE MALDI-TOF MS: [M+H]-=1238.6 (C52H92N20O9S3=1237.63). Patent; Cyclacel Limited; US2002/98236; (2002); (A1) English View in Reaxys H-Cys-βAla-Arg-Arg-Met-Lys-Trp-Lys-LysNH

Rx-ID: 24075430 View in Reaxys 539/630

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Yield

Conditions & References 5 : H-Cys-βAla-Arg-Arg-Met-Lys-Trp-Lys-Lys-NH, Example 5 H-Cys-βAla-Arg-Arg-Met-Lys-Trp-Lys-Lys-NH, Starting from Rink Amide AM resin (0.69 mmol/g, Novabiochem), H-Cys(Trt)-βAla-Arg(Pmc)-Arg(Pmc)-MetLys(Boc)-Trp-Lys(Boc)-Lys(Boc)-resin was assembled. After deprotection (1.5 h), the crude peptide was obtained by precipitation from Et2O, centrifugation/decantation, and drying. Aliquots (total 246 mg) were purified by preparative RP-HPLC (6.5-16.5percent MeCN gradient) to afford the pure title compound (106.4 mg). Anal. RP-HPLC: tR=15.8 min (6.5-16.5percent MeCN gradient, purity>95percent, λ=214 nm). DE MALDI-TOF MS: [M+H]-=1205.4 (C52H92N20O9S2=1205.55). Patent; Cyclacel Limited; US2002/98236; (2002); (A1) English View in Reaxys N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-(tetrahydro-2-oxo-1(2H)-pyrimidinyl)-4-(methylaminocarbonyl)]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate

Rx-ID: 24075436 View in Reaxys 540/630 Yield

Conditions & References 47 : N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-(tetrahydro-2-oxo-1(2H)-pyrimidinyl)-4-(methylaminocarbonyl)]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate (1:1:2) Example 47 N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-(tetrahydro-2-oxo-1(2H)-pyrimidinyl)-4-(methylaminocarbonyl)]-1-piperidinyl]butyl]N-methyl-3-cyano-1-naphthamide Citrate Hydrate (1:1:2) Using standard reductive amination conditions (except that acetic acid-sodium acetate buffer was substituted for acetic acid) N-[(S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-1-naphthamide (145 mg, 0.34 mmol) was reacted with 4-(tetrahydro-2-oxo-1(2H)-pyrimidinyl)-4-(methylaminocarbonyl)piperidine (Miller, S C; WO 9512577) (79.1 mg, 0.329 mmol), converted to the citrate salt, and isolated by filtration from Et2O to afford the title compound (162.5 mg) as a white powder. MS m/z 649 (M+H); analysis for C34H38Cl2N6O3.C6H8O7.2.0 H2O: calculated: C, 54.73; H, 5.74; N, 9.57; found: C, 54.92; H, 5.41; N, 9.29. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys N-[2-(S)-(3,4-Dichlorophenyl)-4-[4-[(R,S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate

Rx-ID: 24075437 View in Reaxys 541/630 Yield

Conditions & References 7 : N-[2-(S)-(3,4-Dichlorophenyl)-4-[4-[(R,S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1naphthamide Citrate Hydrate Example 7 N-[2-(S)-(3,4-Dichlorophenyl)-4-[4-[(R,S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate Using standard reductive amination conditions (except that acetic acid-sodium acetate buffer was substituted for acetic acid) N-[(S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-1-naphthamide (255 mg, 0.60 mmol) was reacted with 4-[(RS)-2-methylsulfinyl-phenyl]piperidine (Shenvi, A B; Jacobs, R T; Miller, S C; Ohnmacht, C J Jr; Veale, C A.: WO 9516682) (201 mg, 0.595 mmol). converted to the citrate salt, and isolated by filtration from Et2O to afford the title compound (290.7 mg) as a white powder. MS m/z 632 (M+H); analysis for C35H35Cl2N3O2S.C6H8O7.H2O: calculated: C, 58.43; H, 5.38; N, 4.98; found: C, 58.20; H, 5.28; N, 4.95. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys N-[2-(S(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1piperidinyl]butyl]-N-methyl-3,4-dicyano-1-naphthamide Citrate Hydrate

Rx-ID: 24075445 View in Reaxys 542/630

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Yield

Conditions & References 12 : N-[2-(S(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3,4-dicyano-1naphthamide Citrate Hydrate Using standard acylation conditions 3,4-dicyano-1-naphthoyl chloride was reacted with N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methylamine (271 mg, 0.597 mmol), converted to the citrate salt, and isolated by filtration from Et2O to afford the title compound (291.7 mg) as a white powder. MS m/z 657 (M+H); analysis for C36H34Cl2N4O2S.C6H8O7.H2O: calculated: C, 58.13; H, 5.11; N, 6.46; found: C, 58.20; H, 5.03; N, 6.36. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys H-Cys-D-Arg-D-Gln-D-Ile-D-Lys-D-Ile-D-Trp-D-Phe-D-Gln-DAsn-D-Arg-D-Arg-D-Nle-D-Lys-D-Trp-D-Lys-D-Lys-NH2

Rx-ID: 24145873 View in Reaxys 543/630 Yield

Conditions & References 13 : H-Cys-D-Arg-D-Gln-D-Ile-D-Lys-D-Ile-D-Trp-D-Phe-D-Gln-D-Asn-D-Arg-D-Arg-D-Nle-D-Lys-D-Trp-D-Lys-DLys-NH2 (SEQ ID No. 27) Example 13 H-Cys-D-Arg-D-Gln-D-Ile-D-Lys-D-Ile-D-Trp-D-Phe-D-Gln-D-Asn-D-Arg-D-Arg-D-Nle-D-Lys-D-Trp-D-Lys-D-Lys-NH2 (SEQ ID No. 27) Starting from Rink Amide AM resin (0.69 mmol/g, Novabiochem), H-Cys(Trt)-D-Arg(Pmc)-D-Gln(Trt)-D-Ile-DLys(Boc)-D-Ile-D-Trp-D-Phe-D-Gln(Trt)-D-Asn(Trt)-D-Arg(Pmc)-D-Arg(Pmc)-D-Nle-D-Lys (Boc)-D-Trp-D-Lys(Boc)-DLys(Boc)-resin (SEQ ID No. 27) was assembled. After deprotection (1.5 h), the crude peptide was obtained by precipitation from Et2O, centrifugation/decantation, and drying. Aliquots (total 246 mg) were purified by preparative RP-HPLC (17.5-27.5percent MeCN gradient) to afford the pure title compound (45.9 mg). Anal. RP-HPLC: tR=16.9 min (17.5-27.5percent MeCN gradient, purity>99percent, l=214 nm). DE MALDI-TOF MS: [M+H]+=2330.3 (C108H176N36O20S=2330.85). Patent; Cyclacel Limited; US6472507; (2002); (B1) English View in Reaxys (E/Z) Methyl 1-(4-[2-(2-Phenyl-4-oxazolyl)ethoxy]phenylsulfonyl)-2-N,N-dimethylamino Acrylate

Rx-ID: 24145875 View in Reaxys 544/630 Yield 1.10 g (64%)

Conditions & References 1.C : (C) (C) (E/Z) Methyl 1-(4-[2-(2-Phenyl-4-oxazolyl)ethoxy]phenylsulfonyl)-2-N,N-dimethylamino Acrylate A stirred solution of 1.5 g (3.7 mM) of the compound prepared in (B) above in 20 mL of Dioxane was treated with 1.2 mL (9.0 mM) of DMA and heated to reflux 7 h. The mixture was kept at rt overnight and then concentrated in vacuo. Trituration of the residue with Et2O produced a solid which was recrystallized from MeOH to provide 1.10 g (64percent) of product as nearly white crystals, mp 111-114° C. Anal. Cal. For C23H24N2O6S (MW 456): C, 60.51; H, 5.30; N, 6.14. Found: C, 60.58; H, 5.29; N, 6.09 NMR(CDCl3) 2.95 (broad s, 3H), 3.15(t, 2H),3.30 (broad s, 3H), 3.60 (s, 3H), 4.45(t, 2H), 7.20(d, 2H),7.55 (m, 3H)7.55,7.85(d,2H), 7.95(m, 2H), 8.05(s, 1H)] MS (FD+) m/e 456 IR(KBr) 1609, 1614, 1590 cm-1 Patent; Eli Lilly and Company; US6617342; (2003); (B1) English View in Reaxys

PEG t-Boc amine

Rx-ID: 24145876 View in Reaxys 545/630 Yield

Conditions & References 2 : Preparation of N-maleimidyl poly(ethylene glycol) amine

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The above described crude N-maleimidyl PEG t-Boc amine was purified by ion exchange chromatography. The crude product (1.45 g in 100 ml deionized water) was loaded onto DEAE Sepaharose, 100 ml) and eluted with aqueous NaCl (15percent, pH 3). The eluent was extracted with CH2Cl2 (3*100 ml) and the extract was dried over Na2SO4, evaporated to dryness and precipitated with ethyl ether (100 ml). The precipitate was collected by filtration and dried under vacuum at room temperature to yield 0.7 g of N-maleimidyl PEG t-Boc amine The 1H nmr was consistent with that of N-maleimidyl PEG t-Boc amine (1H nmr: dmso-d6: 1.37 ppm, t-butyl; 3.51, PEG backbone; 7.03, HC=CH). Patent; Shearwater Corporation; US6602498; (2003); (B2) English View in Reaxys

MPEG-Diethanolamine

Rx-ID: 24217550 View in Reaxys 546/630 Yield

Conditions & References Preparation of MPEG-DEA (Step 2, Chart A) Preparation of MPEG-DEA (Step 2, Chart A) MPEG-Diethanolamine (MPEG-DEA) was prepared from MPEG-Cl 750 by reaction with Diethanolamine (DEA) in water. To 3.98 g of MPEG-Cl (5.18 mmoles) dissolved in 70 mL of water was added 3.58 g K2 CO3 (25.0 mmoles) and 2.73 g of DEA (25.96 mmoles). The mixture was refluxed for 24 hours. After cooling, 17.5 g of Na2 SO4 were added to form two phases and the upper polymer phase containing the product was collected. The upper phase was extracted once with 100 mL of chloroform/ethanol (1:1.5, v:v), dried over anhydrous MgSO4 and concentrated by distillation of the solvent. The solid residue was dissolved in 10 mL of chloroform and precipitated with 100 mL of diethyl ether at -20° C. The product was dried under vacuum to yield 2.69 g (62percent yield) of MPEG-DEA (MW 837.14). FTIR results indicate nearly complete conversion to the product: (neat) 3468 cm-1 (OH), disappearance of C-Cl absorbance at 663 cm-1. Patent; Baxter Biotech Technology Sarl; US5907035; (1999); (A1) English View in Reaxys (7R)-7- [(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)aceta mido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem4-carboxylate, trifluoroacetic acid salt

Rx-ID: 24294558 View in Reaxys 547/630 Yield

Conditions & References 17 : (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3cephem-4-carboxylate, trifluoroacetic acid salt Example 17 (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4carboxylate, trifluoroacetic acid salt (7R)-7-[(Z)-2-(N-triphenylmethylaminothiazol-4-yl)-2-(triphenylmethoxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, 4-methoxybenzyl ester(40 mg) was dissolved in 0.1 ml of anisole and 0.9 ml of dichloroacetic acid. The resulting mixture was stirred at room temperature for 3 hours and then precipitated by addition of diethyl ether (100 ml). The precipitate was filtered and subjected to HP-20 reverse phase chromatography to give the title compound. 1H NMR (D2 O) δ3.60 (q, 2H, J=6), 4.60 (q, 2H, J=10), 5.20 (d, 1H, J=4), 5.80 (d, 1H, J=4), 6.90 (s, 1H), and 9.13 (s, 1H). IR (KBr) 997, 1042, 1180, 1349, 1386, 1533, 1615, 1655, and 1768 cm-1. Patent; Microcide Pharmaceuticals, Inc.; US6030965; (2000); (A1) English View in Reaxys (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)aceta mido]-3(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, trifluoroacetic acid salt

Rx-ID: 24294559 View in Reaxys 548/630

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Yield

Conditions & References 17 : (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3cephem-4-carboxylate, trifluoroacetic acid salt Example 17 (7R)-7-[(Z)-2-(aminothiazol-4-yl)-2-(hydroxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4carboxylate, trifluoroacetic acid salt (7R)-7-[(Z)-2-(N-triphenylmethylaminothiazol-4-yl)-2-(triphenylmethoxyimino)acetamido]-3-(4-isothioureidomethylthiazol-5-ylthio)-3-cephem-4-carboxylate, 4-methoxybenzyl ester(40 mg) was dissolved in 0.1 ml of anisole and 0.9 ml of dichloroacetic acid. The resulting mixture was stirred at room temperature for 3 hours and then precipitated by addition of diethyl ether (100 ml). The precipitate was filtered and subjected to HP-20 reverse phase chromatography to give the title compound. 1H NMR (D2 O) δ3.60 (q, 2H, J=6), 4.60 (q, 2H, J=10), 5.20 (d, 1H, J=4), 5.80 (d, 1H, J=4), 6.90 (s, 1H), and 9.13 (s, 1H). IR (KBr) 997, 1042, 1180, 1349, 1386, 1533, 1615, 1655, and 1768 cm-1. Patent; Microcide Pharmaceuticals, Inc.; US6025352; (2000); (A1) English View in Reaxys 4-Cyano-5-(dimethylamino-methyleneamino)-3(3-methoxy-benzylamino-pyrazole

Rx-ID: 24294560 View in Reaxys 549/630 Yield

Conditions & References 45.3 : 4-Cyano-5-(dimethylamino-methyleneamino)-3-(3-methoxy-benzylamino-pyrazole Step 45.3 4-Cyano-5-(dimethylamino-methyleneamino)-3-(3-methoxy-benzylamino-pyrazole A mixture of 9.12 g (37.5 mmol) of 5-amino-4-cyano-3-(3-methoxy-benzylamino)-pyrazole, 7.71 ml (45 mmol) of N,Ndimethylformamide diethyl acetal and 130 ml of toluene is heated under reflux for 3 hours and then approx. 40 ml of hexane are added dropwise thereto. Cooling to 10° C. causes a crystalline precipitate to form. Filtering and washing the filter residue with diethyl ether yield the title compound; m.p. 136-137° C. Patent; Novartis AG; US5981533; (1999); (A1) English View in Reaxys 17-beta-cyano -3,3-ethylenedioxy-9-alpha-hydroxy-17-alpha-(tetrahydropyran -2'-yloxy)-androst-5-ene

Rx-ID: 24442035 View in Reaxys 550/630 Yield

Conditions & References 25 : 17-Beta-cyano-3,3-ethylenedioxy-9-alpha-hydroxy-17-alpha-(tetrahydropyran -2'-yloxy)-androst-5-ene EXAMPLE 25 17-Beta-cyano-3,3-ethylenedioxy-9-alpha-hydroxy-17-alpha-(tetrahydropyran -2'-yloxy)-androst-5-ene p-Toluenesulfonic acid monohydrate (50 mg) was added to a stirred solution of 17-beta-cyano-3,3-ethylenedioxy-9alpha, 17-alpha-dihydroxyandrost-5-ene (5.0 g) in methylene chloride (10 ml) and 2,3-dihydropyran (10 ml). After stirring for 3 hours at room temperature pyridine (2 ml) was added and the reaction mixture was poured into water. The phases were separated and the aqueous layer was extracted with methylene chloride (10 ml). The combined organic layers were dried and concentrated under reduced pressure to an oil. Crystallization of the oil from diethyl ether yielded 4.5 g of the title compound, as a mixture of two diastereomers. M.p.: 210° C. (decomp.) NMR (CDCl3): 0.972, 0.995 (C18 H3), 1.176 (C19 H3), 3.58, 3.91 (2x m, 2H), 3.91 (ethylenedioxy-H), 5.01, 5.05(2x tr, 1H), 5.36 (C6 H). Patent; Gist-Brocades N.V.; US5352809; (1994); (A1) English View in Reaxys

7-(βalanyl)paclitaxel

Rx-ID: 24443160 View in Reaxys 551/630

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Yield

Conditions & References 9 : 7-(βalanyl)paclitaxel EXAMPLE 9 7-(βalanyl)paclitaxel To a solution of 135 mg of 7-(carbobenzyloxy-βalanyl)paclitaxel in 20 ml of methanol and 13 ml of formic acid, was added 200 mg of Pd/C 5percent. The reaction mixture was stirred for 6 hours at room temperature. The catalyst was filtered, washed with methanol and the solvents were evaporated to dryness under vacuum. The residue was dissolved in 8 ml of methanol and precipitated with 150 ml of diethylether, affording 85 mg of the title compound. FAB-MS: M/z 925, M+H +; 947, M+Na +1 H NMR(400 MHz, CDCl3): δ 1.14 (s,3H,CH3 -16) 1.20(s,3H,CH3 -17) 1.79 (s,3H,CH3 -19) 1.85 (s, 3H,CH3 -18) 2.17(s,3H,CH3 CO-10) 2.2-2.6(m,6H,CH2 -14+CH2 -6+OCOCH2 CH2 NH2) 2.42(s,3H,CH3 CO-4) 3.0-3.2(m,2H,OCOCH2 CH2 NH2) 3.90(d,J=6.8 Hz,1H, 3) 4.18, 4.31(two d, J=8.2 Hz,2H,CH2 -20) 4.80(d,J=3.2 Hz,1H,2') 4.91(d,J=8.5 Hz,1H,5) 5.62(dd,J=10.2 Hz, J=7.0 Hz,1H,7) 5.66 (d,J=6.8 Hz,1H,2) 5.81(dd,J=2.9 Hz, J=9.1 Hz,1H,3' 6.17 (m,1H,13) 6.19(s,1H,10) 7.3-8.2 (m,16H,NH-4'+3-Ph) Patent; Farmitalia Carlo Erba S.r.l.; US5362831; (1994); (A1) English View in Reaxys

(S)-Tfc-(L)-Leu-(L)-TrpOMe

Rx-ID: 24520406 View in Reaxys 552/630 Yield

Conditions & References 18 : Synthesis and pharmacological activity of (S)-Tfc-(L)-Leu-(L)-TrpOMe (compound 18) EXAMPLE 18 Synthesis and pharmacological activity of (S)-Tfc-(L)-Leu-(L)-TrpOMe (compound 18) A suspension of 0.500 g (5.21 mmoles) of (-)tetrahydrofuran-2-carboxylic acid (Aldrich) in 50 ml of dry methylene chloride (CH2 Cl2) was brought under argon atmosphere to the temperature of an ice and salt bath. The following were then added in succession under stirring: 0.880 g (5.21 mmoles) of commercial hydroxybenzotriazole (HOBt) and 1.070 g (5.19 mmoles) of N.N'-dicyclohexylcarbodiimide (DCC). After 10 minutes, a further 1.900 g (5.16 mmoles) of (L)-Leu-(L)-TrpOMe.HCl (Novabiochem) and 0.570 ml (5.17 mmoles) of 4-methylmorpholine (NMM) were added, maintaining the temperature of the bath for a further 2 hours. The mixture was then left, under static argon, out of the light, and with the temperature free to rise to room temperature, under stirring for 12 hours. The white precipitate was then filtered away and washed with a little CH2 Cl2. The latter was put back into the pale yellow coloured filtered reaction solution, which was dried out under vacuum. The yellowish solid thus obtained was ground with an excess of water and the aqueous solution, after extraction with ethyl acetate, was treated under stirring for 12 hours with ion-exchange resin Bio-Rad AG-501 X8 (D). On filtering away the resin, the aqueous solution was freeze-dried and the white solid thus recovered was ground with anhydrous ethyl ether, discarding the organic phase after decanting. The analytically pure white solid thus obtained (1.660 g, 74.8percent) was separated into its two diastereoisomers by flash-chromatography in an inverted phase (resin C18, eluant CH3 CN 30/H2 O 70 v/v), recovering the fractions of interest which, when joined together, concentrated and freeze-dried in their turn, give 0.580 g (34.9percent with respect to the pure diastereoisomeric pair) of an analytically pure white solid. Patent; Polifarma S.p.A.; US5504071; (1996); (A1) English View in Reaxys Boc-N(CH2 COOH)--CH2 --CO-Pro-O--(CH2)3 --NHlt;-Glylt;Fmoc

Rx-ID: 24596666 View in Reaxys 553/630 Yield

Conditions & References 6 : Boc-N(CH2 COOH)--CH2 --CO-Pro-O--(CH2)3 --NH<-Gly<-Fmoc (3) Boc-N(CH2 COOH)--CH2 --CO-Pro-O--(CH2)3 --NH<-Gly<-Fmoc (3) To a solution of tert-butyloxycarbonyl-iminodiacetic acid anhydride (0.62 g, 2.8 mmol) in DMF (3 ml), Pro-O(CH2)3 NH<-Gly<-Fmoc (0.76 g, 1.7 mmol) in DMF (10 ml) was added. The amino component was prepared from the corresponding trifluoroacetate as follows: TFA, Pro-O(CH2)3 NH<-Gly<-Fmoc was dissolved in ethyl acetate and extracted into aqueous 1M hydrochloric acid.

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The aqueous phase was then adjusted to pH 9 by adding a saturated solution of Na2 CO3 and immediately extracted with chloroform at 5° C. After drying over MgSO4, solvent was evaporated to dryness. The reaction mixture was stirred for 6 hrs and then evaporated to dryness. The residue was dissolved in methanol and precipitated by adding diethylether to remove remaining Boc-IDA anhydride. The crude product that was obtained was crystallized from a solvent mixture of ethyl acetate and petroleum ether. Yield 0.63 g (57percent); 1 H-NMR (300 MHz, DMSO-d6, 25° C.) δ: 1.35 (s, 9H, BOC), 1.71 (m, 2H, PA Cδ H2), 1.85, 2.14 (m, 2H, Pro Cδ H2), 1.91 (m, 2H, Pro Cγ H2), 3.13 (m, 2H, PA Cγ H2), 3.58 (d, 2H, Gly Cα H2), 3.75-4.16 (m, 4H, IDA), 4.05 (m, 2H, PA Cα H2), 4.32 (m, 1H, Pro Cα H), 4.18-4.32 (m, 3H, Fmoc OCH2 --CH--), 7.47 (t, 1H, Gly NH), 7.33-7.84 (m, 8H, Fmoc), 7.85 (t, 1H, PA NH). Patent; Selectide Corporation; US5635598; (1997); (A1) English View in Reaxys

N-BOC-aziridines

Rx-ID: 24596667 View in Reaxys 554/630 Yield

Conditions & References 89 : 6-methyl-7-bromo-1H-indole-3-ethanamine Elemental Analysis: C 45.54; H 4.80; N 9.47. For Examples 90 through 110, where applicable, diethylether was distilled from sodium benzophenone ketyl prior to use. All reactions were performed under a positive pressure of argon. 1 H-NMR and 13 C-NMR data were recorded on a Bruker AC-200P (200 MHz). IR spectra were obtained on Nicolet 510 P-FT (film and KBr). Melting points were determined on a Buchi apparatus and are not corrected. Analytical TLC was performed on Merck TLC glass plates precoated with F254 silica gel 60 (UV, 254 nm and Iodine). Chromatographic separations were performed by using 230-400 mesh silica gel (Merck). N-BOC-aziridines (2a-d) were prepared from the corresponding alkenes following standard procedures. Patent; Eli Lilly and Company; US5688807; (1997); (A1) English View in Reaxys

Dimethylbenzothiazolium monocarbothiophene iodide

Rx-ID: 24596668 View in Reaxys 555/630 Yield

Conditions & References I : Synthesis of Dimethylbenzothiazolium monocarbothiophene iodide Example I Synthesis of Dimethylbenzothiazolium monocarbothiophene iodide A mixture of 0.24 g (1.26 mmol) of 5-bromo-2-thiophene-carboxaldehyde and 0.185 mL of triethylamine in 10 mL of acetonitrile was added with 0.84 g (2.89 mmole) of 1,2-dimethylbenzothiazolium iodide. The reaction mixture was slowly heated to reflux for 16 hours. The initial color was yellow. It turned red as temperature increased to 67° C. and it was dark green when the reaction was completed. The final product was recrystallized by dissolution in methanol and precipitation from ethyl ether; yield 70 mg: 1 H NMR (300 MHz, DMSO-d6) d 3.18, 3.37, 3.7, 4.2, 4.3, 6.70-8.5 ppm; 13 C NMR (75.6 MHz, DMSO-d6) d 18.1, 37.2, 117.9, 125.4, 125.6, 129.1, 130.4 ppm. UV-vis (methanol) lmax (e, mol-1 dm3 cm-1) 707 (14,000) nm; ESI-MS m/z for M+ is 419 which corresponds to C27 H31 N2 S3. Patent; Fung; Ella Y.; Rajagopalan; Raghavan; US5723104; (1998); (A1) English View in Reaxys

Petroleum ether Rx-ID: 24822626 View in Reaxys 556/630

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Yield

Conditions & References 20.F : Preparation of tert-butyl (1S,4R,6R,7R)-3-methylene-1-oxo-7-phenylacetamidocepham-4-carboxylate from (1S,6R,7R)-4-tertbutoxycarbonyl-1-oxo-phenylacetamido-3-triphenylphosphoniomethyl-3-cephem bromide. F. The process according to Example 19 was repeated but, instead of stannous chloride, sodium stannite was used which was formed in situ by adding to the suspension of the cephem bromide compound (750 mg) in 15 ml of tetrahydrofuran a solution of 385 mg of stannous chloride dihydrate and 100 mg of sodium chloride in 5 ml of water, of which the pH was adjusted to 9 with a 4N sodium hydroxide solution. After heating the reaction mixture up to 40° C. and maintaining the pH at 9 with a 1N sodium hydroxide solution, the reaction mixture was stirred for 90 minutes and cooled down to room temperature. After adjusting the pH to 7 and pouring out the reaction mixture into 60 ml of ethyl acetate the layers were separated, the water layer extracted with 3*30 ml of ethyl acetate and the combined organic layers were washed with brine. The ethyl acetate solution, containing 92percent of the title compound as determined by HPLC analysis was concentrated to dryness. The residue was then dissolved in acetone and precipitated with diethylether and petroleum ether 40°-60° C. Isolation by centrifugation, washing and drying gave 490 mg of the title compound with a purity of 61percent. Yield 88percent. Patent; Gist-Brocades N.V.; US4985554; (1991); (A1) English View in Reaxys

bisurethane bisphenol

Rx-ID: 24993020 View in Reaxys 557/630 Yield

Conditions & References 5 : EXAMPLE 5 EXAMPLE 5 A solution of 10 mmol. of 2-(4-hydroxyphenyl)-2-(4-methylaminophenyl)propane and 5 mmol. of bisphenol A bischloroformate in 50 ml. of methylene chloride was placed in a small blender and agitated for 10 minutes, during which time a precipitate formed. There was then added a solution of 15 mmol. of sodium carbonate in 50 ml. of water, and the mixture was blended for an additional 11/2 hours. The organic layer was separated, dried with phase separation paper and stripped in a rotary evaporator to yield a fluffy white solid. The solid was washed twice with hexane, dissolved in a small amount of methylene chloride and precipitated slowly by the addition of ethyl ether. The precipitate was filtered, washed twice with ether and dried to yield the desired bisurethane bisphenol having the formula STR7 Patent; General Electric Company; US4767877; (1988); (A1) English View in Reaxys 6-[2-(1-Dimethylamino-3-oxo-butene-2-yl)]-3,4-dihydrocarbostyril

Rx-ID: 25002594 View in Reaxys 558/630 Yield

Conditions & References 1.4 : Step 4. Step 4. 6-[2-(1-Dimethylamino-3-oxo-butene-2-yl)]-3,4-dihydrocarbostyril A mixture of the oxo compound obtained in Step 3. above (750 mg), dimethyl formamide dimethyl acetal (5 ml) and pyridine (0.3 ml) stirred under nitrogen at a temperature of 75°-80° C. for about 22 hours. The reaction mixture is cooled to 0° C., filtered and the resulting precipitate rinsedwith cold ethyl ether and dried in vacuo, this affording the desired crude product as a solid, M.P.=178°-180° C. Patent; Rorer Pharmaceutical Corporation; US4785005; (1988); (A1) English View in Reaxys

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7-(3-cyclohexylureido)-3-desacetoxy-cephalosporanic acid

Rx-ID: 25212260 View in Reaxys 559/630 Yield

Conditions & References 23 : EXAMPLE 23 EXAMPLE 23 In a 1 liter reaction flask and to 5.360 g of 7-amino-3-desacetoxy-cephalosporanic acid (7-ADCA) are added pyridine (500 ml) and cyclohexylisocyanate (4.8 ml). The mixture is heated at 50° C for 4 hrs. and at 70° C for 3 hrs. The solvent is removed by evaporation under reduced pressure, the residue is taken up in acetic acid (20 ml) and ethyl acetate (250 ml) from which 7-(3-cyclohexylureido)-3-desacetoxy-cephalosporanic acid precipitates by addition of ethyl ether (1 liter). Rf = 0.37 (+- 0.10) in the system methylisobutylketone/methanol/formic acid 60/6/2, detection with bromeresol green and KMnO4; nmr: 1.0-1.8 m (6H), 1.4-2.1 m (4H), 2.04 s (3H), 3.31 d (1H) (J 14.7 c./sec.), 3.4-3.9 m (1H), 3.66 d (1H) (J 14.7 c./sec.), 5.04 d (1H) (J 5.3 c./sec.), 5.61 d (1H) (J 5.3 c./sec.). Patent; Recherche et Industrie Therapeutiques (R.I.T.); US3994886; (1976); (A1) English View in Reaxys

7-(3-isopropylureido)-3-desacetoxy-cephalosporanic acid

Rx-ID: 25212261 View in Reaxys 560/630 Yield

Conditions & References 10 : EXAMPLE 10 EXAMPLE 10 In a 1 liter reaction flask and to 5.360 g. of 7-amino-3-desacetoxy-cephalosporanic acid (7-ADCA) are added chloroform (250 ml), triethylamine (10 ml) and isopropylisocyanate (3.7 ml). The mixture is heated to 50° C for 10 hrs. The unreacted 7-ADCA is separated by filtration. The solvent is removed by evaporation under reduced pressure, the residue is dissolved in acetone and precipitated by addition of ethyl ether. After filtration, the precipitate is taken up in acetic acid (30 ml) from which 7-(3-isopropylureido)-3-desacetoxy-cephalosporanic acid precipitates by addition of ethyl ether (200 ml). Rf = 0.25 (+- 0.10) in the system methylisobutylketone/methanol/formic acid 60/6/2, detection with bromcresol green and KMnO4; nmr: 1.04 d (6H) (J 6.6 c./sec.), 2.01 s (3H), 2.8-3.5 m (1H) (J 6.6 c./sec.), 3.29 d (1H) (J 15.5 c./sec.), 3.67 d (1H) (J 15.5 c./sec.), 5.02 d (1H) (J 4.8 c./sec.), 5.60 d (1H) (J 4.8 c./sec.). Patent; Recherche et Industrie Therapeutiques (R.I.T.); US3994886; (1976); (A1) English View in Reaxys trifluoroacetic salt of 3-(3-methoxyprop-1-(t)-enyl)-7β-(α-amino-αphenylacetamido)-ceph-3-em-4-carboxylic acid

Rx-ID: 25283367 View in Reaxys 561/630 Yield

Conditions & References 16 : EXAMPLE 16 The above obtained acid is stirred for 30 minutes at 0° C in a mixture of 1 ml. of anisole and 6 ml. of trifluoroacetic acid. Thereafter, the solvents are removed under reduced pressure and the resulting residue mixed with ethyl ether and the mixture to afford the trifluoroacetic salt of 3-(3-methoxyprop-1-(t)-enyl)-7β-(α-amino-α-phenylacetamido)-ceph-3em-4-carboxylic acid. Patent; Syntex (U.S.A.) Inc.; US4112087; (1978); (A1) English View in Reaxys trifluoroacetic acid salt of 3-[3-(2-methyl-1,3,4-thiadiazol-5-ylthio)-prop-1-(t)-enyl]-7β-amino-ceph-3-em-4-carboxylic acid

Rx-ID: 25283369 View in Reaxys 562/630 Yield

Conditions & References 14 : EXAMPLE 14

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EXAMPLE 14 This example illustrates step 7 of the first process described for preparing the compounds of the invention. In this example, 2.5 ml. of trifluoroacetic acid is added to a stirring mixture of 200 mg. of benzhydryl 3-[3-(2-methyl-1,3,4-thiadiazol-5-ylthio)-prop-1-(t)-enyl]-7β-amino-3-em-4-carboxylate and 0.5 ml. of anisole at 0° C. After three minutes, the mixture is evaporated to dryness and the resulting residue mixed with ethyl ether affording the crystalline trifluoroacetic acid salt of 3-[3-(2-methyl-1,3,4-thiadiazol-5-ylthio)-prop-1-(t)-enyl]-7β-amino-ceph-3em-4-carboxylic acid which is then collected by filtration. Patent; Syntex (U.S.A.) Inc.; US4139618; (1979); (A1) English View in Reaxys 7β-[(EZ)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(hydroxyiminoacetamido]-3-[(E)-2-((RS)-2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4-carboxylate

Rx-ID: 25360607 View in Reaxys 563/630 Yield

Conditions & References 3 : Physicochemical properties (3) A 251 mg (0.27 mmol) portion of the compound obtained in the above step (2) and 0.2 ml of anisole were dissolved in 2 ml of methylene chloride, the resulting solution was mixed with 2 ml of trifluoroacetic acid, and the mixture was stirred for 1 hour at room temperature. The reaction solution was concentrated under a reduced pressure, the residue was again mixed with 2 ml of trifluoroacetic acid and 4 ml of methylene chloride, and the mixture was stirred for 1 hour at room temperature. The reaction solution was concentrated under a reduced pressure, and the resulting residue was mixed with ethyl ether to obtain 167 mg of crude product. This was purified by HP-20 column chromatography to obtain 135 mg of 7β-[(EZ)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2(hydroxyiminoacetamido]-3-[(E)-2-((RS)-2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4-carboxylate. This was further purified by a high performance liquid chromatography to obtain two components (26A and 26B) based on the oxime E,Z of the above compound. These were diastereomer mixtures based on the isooxazolidine at the 5-position. Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys p-methoxybenzyl 7β-[(Z)-2-(2-tritylamino-1,2,4-thiadiazol-3-yl)-2methoxyiminoacetamido]-3-[(E)-2-(2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4-carboxylatemiddot;iodide

Rx-ID: 25360609 View in Reaxys 564/630 Yield

Conditions & References

827 mg (93%)

2 : Physicochemical properties (2) A 766 mg (0.89 mmol) portion of the compound obtained in the above step (1) was dissolved in 4 ml of DMF, and the resulting solution was mixed with 277 μl of methyl iodide (4.5 mmol) and the mixture was stirred overnight at room temperature. Thereafter, the solvent was evaporated under a reduced pressure, and the resulting residue was solidified by adding ethyl ether, collected by filtration and then dried to obtain 827 mg (93percent) of p-methoxybenzyl 7β-[(Z)-2-(2-tritylamino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[(E)-2-(2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4carboxylate*iodide. Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys

p-methoxybenzyl 7β-[(Z)-2-(5-tert-butoxycarbonylamino-1,2,4thiadiazol-3-yl)-2-(1-methoxy-1-methyl)ethoxyiminoacetamido]-3[(E)-2-((RS)-2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4carboxylatemiddot;iodide

Rx-ID: 25360610 View in Reaxys 565/630 Yield

Conditions & References 2 : Physicochemical properties (2)

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A 230 mg (0.30 mmol) portion of the compound obtained in the above step (1) was dissolved in 4 ml of DMF, the solution was mixed with 93 μl (1.5 mmol) of methyl iodide, and the mixture was stirred overnight at room temperature. The solvent was evaporated under a reduced pressure, and the resulting residue was solidified by adding ethyl ether, collected by filtration and then dried to obtain 251 mg of p-methoxybenzyl 7β-[(Z)-2-(5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2-(1-methoxy-1-methyl)ethoxyiminoacetamido]-3-[(E)-2-((RS)-2,2-dimethyl-5-isooxazolidinio)vinyl]-3-cephem-4-carboxylate*iodide. Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys sodium 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-[1,3-dioxo-2-methyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1.2-a)pyridazin-5-yl]-3-cephem-4-carboxylate

Rx-ID: 25360611 View in Reaxys 566/630 Yield

Conditions & References 2 : Physicochemical properties (2) In an atmosphere of argon, 160 mg (0.18 mmol) of p-methoxybenzyl 7β-[(Z)-2-(2-tritylamino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-[1,3-dioxo-2-methyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]-3-cephem-4-carboxylate obtained in the above step (1) was dissolved in methylene chloride (3 ml) and anisole (2 ml). To the resulting solution cooled at 10°C was added dropwise trifluoroacetic acid (5 ml). After 60 minutes of stirring at 10°C to room temperature, the solvent and trifluoroacetic acid were evaporated under a reduced pressure, and the thus obtained residue was solidified by adding ethyl ether-hexane and collected by filtration. This was added to trifluoroacetic acid (10 ml) cooled at 10°C, and water (5 ml) was added dropwise to the resulting mixture. After 60 minutes of stirring at room temperature, trifluoroacetic acid was evaporated under a reduced pressure, and the resulting residue was mixed with ethyl alcohol and subjected to azeotropic distillation to remove water. The resulting residue was solidified by adding ethyl ether and collected by filtration. The thus obtained powder was dissolved in saturated sodium bicarbonate aqueous solution and purified using an HP-20 column to obtain sodium 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3-[1,3-dioxo-2-methyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1.2-a)pyridazin-5-yl]-3-cephem-4-carboxylate (74 mg). Patent; YAMANOUCHI PHARMACEUTICAL CO. LTD.; EP691343; (1996); (A1) English View in Reaxys

deglucoteicoplanin

Rx-ID: 25414447 View in Reaxys 567/630 Yield

Conditions & References 19 : Preparation of deglucoteicoplanin from antibiotic L 17046 This solution is treated in the same manner as in Example 18. The crude product (precipitated by addition of ethyl ether) is purified as in the last part of Example 4 yielding 900 mg of substantially pure deglucoteicoplanin. Patent; GRUPPO LEPETIT S.p.A.; EP146053; (1991); (B1) English View in Reaxys Trans -D,L-cyclohexane-1,2-dicarboxylate monoamide of Cha-Asp-Leu-NHEt

Rx-ID: 25414451 View in Reaxys 568/630 Yield

Conditions & References B.6 : Step 6: Step 6: Synthesis of Trans-D,L-cyclohexane-1,2-dicarboxylate monoamide of Cha-Asp-Leu-NHEt . A solution of H-Cha-Asp(OtBu-Leu-NHEt (100 mg, 0.21 mmol), DMAP (cat. amount) and trans-(D,L)-cyclohexanedicarboxylic anhydride in DCM (5 mL) was stirred at room temperature for 3 h. Then the solution was diluted with DCM (20 mL), washed with 1N HCl (2 x 10 mL) and brine, then dried and concentrated to obtain 98 mg (73percent) of a white solid. The solid was dissolved in water (1 mL) and TFA (4 mL) and was stirred at room temperature for 1 h.

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Solvents were then distilled off in vacuo. Trituration of the residual oil with diethyl ether yielded 60 mg of a white solid. 1H-NMR (DMSO-6d) δ 8.20, 8.00, 7.90, 7.85, 7.65, 7.60, 7.50 (NHs, 4H), 4.45(m, 1H), 4.14(m, 2H), 3.00(dd, 2H), 2.70(m, 1H), 2.50(m, 1H), 2.41(m, 2H), 2.05-1.05(m, 22H), 1.00(t, 3H), 0.80(dd, 6H), 0.80(m, 2H). The two distereoisomers were separated by preparative HPLC (linear gradient 30percent-90percent B in 25 min) to obtain: R,R-cyclohexane-1,2-dicarboxylate monoamide of Cha-Asp-Leu-NHEt retention time 10min. S,S-cyclohexane-1,2-dicarboxylate monoamide of Cha-Asp-Leu-NHEt (Tab. I, Example No 3): retention time 20 min. Patent; ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.; EP1230260; (2003); (B1) English View in Reaxys

Rhodamine B piperazine amide

Rx-ID: 25614292 View in Reaxys 569/630 Yield

Conditions & References 10 : Synthesis of {9-[2-(4-{3-[4-(4-(3-{4-Carboxy-3-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenyl]-thioureido}-phenyldisulfanyl)-phenylcarbamoyl]-propionyl}-piperazine-1-carbonyl)-phenyl]-6-diethylamino-xanthen-3-ylidene}-diethyl-ammonium Synthesis of Rhodamine B piperazine amide (3). A 2.0 M solution of trimethyl aluminum in toluene (4.5 mmol) was added dropwise to a solution of piperazine (9.1 mmol) in 35 mL of CH2Cl2 at room temperature. After one hour of stirring a white precipitate was observed. A solution of rhodamine B base (2, 2.3 mmol) in 20 mL of CH2Cl2 was added drop wise to the heterogeneous solution. Gas evolution was observed during the addition period. After stirring at reflux for 12 h, a 0.1 M aqueous solution of HCl was added drop wise until gas evolution ceased. The heterogeneous solution was filtered and the retained solids were rinsed with CH2Cl2 and a 4:1 CH2Cl2/MeOH solution. The combined filtrate was concentrated and the residue was dissolved in CH2Cl2, filtered to remove insoluble salts, and concentrated again. The resulting glassy solid was then partitioned between dilute aqueous NaHCO3 and EtOAc. After isolation, the aqueous layer was washed with 3 additional portions of EtOAc to remove residual starting material. The retained aqueous layer was saturated with NaCl, acidified with 1 M aqueous HCl, and then extracted with multiple portions of 2:1 iPrOH/CH2Cl2, until a faint pink color persisted. The combined organic layers were then dried over Na2SO4, filtered, and concentrated under reduced pressure. The glassy purple solid was dissolved in a minimal amount of MeOH and precipitated by drop wise addition to a large volume of Et2O. The product was collected by filtration as a dark purple solid. mp 219-220 ° C. IR: 1630 cm-1. 1H NMR (500 MHz, CD3OD): δ 1.28-1.33 (t, 12, J=7.5), 3.12 (br s, 4), 3.64-3.74 (m, 12), 6.97-6.98 (d, 2, J=2.5), 7.09-7.11 (dd, 2, J=2.5, 10.0), 7.26-7.27 (d, 2, J=9.5), 7.51-7.54 (m, 1), 7.76-7.80 (m, 3). 3C NMR (300 MHz, CD OD) δ13.07, 44.34, 45.59, 47.05, 97.51, 114.87, 115.67, 129.04, 131.50, 131.63, 131.97, 3 132.54, 133.08, 135.75, 156.82, 157.28, 159.32, 169.48. MALDI, m/z calcd 510.31 found 510.29. Patent; Marquette University; US2007/54410; (2007); (A1) English View in Reaxys N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[4-methoxy-(S*)-2methylsulfinyl)phenyl]-1-piperidinyl]butyl]-N-[2-oxo-2-dimethylaminoethyl]-3-cyano-2-methoxy-1-naphthamide citrate

Rx-ID: 25858209 View in Reaxys 570/630 Yield

Conditions & References 50 : N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[4-methoxy-(S*)-2methylsulfinyl)phenyl]-1-piperidinyl]butyl]-N-[2oxo-2-dimethylaminoethyl]-3-cyano-2-methoxy-1-naphthamide citrate Example 50 N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[4-methoxy-(S*)-2methylsulfinyl)phenyl]-1-piperidinyl]butyl]-N-[2-oxo-2-dimethylaminoethyl]-3-cyano-2-methoxy-1-naphthamide citrate

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To a solution of N-[(S)-2-(3,4-dichlorophenyl)-4-[4-[4-methoxy-(S*)-2-(methylsulfinyl)-phenyl]-1-piperidinyl]butyl]-N-[2hydroxy-2-oxoethyl]-3-cyano-2-methoxy-1-naphthamide citrate, N,N-diisopropylethylamine, and dry DCM was added tetramethylfluoroformamidinium hexafluorophosphate (5 equiv.). After 5 min, dimethylamine (2M in THF) (150 equiv.) was then added. After stirring overnight, the mixture was concentrated, and the residue was purified by flash chromatography. The purified free base (45percent) was converted to the citrate salt and isolated by filtration from Et2O. MS APCI, m/ z=763 (M+) (free base); HPLCb 16.5. Patent; Shenvi, Ashokkumar Bhikkappa; US2004/58916; (2004); (A1) English View in Reaxys 3-(2-hydroxy)ethyl-6-methyl-2-(2-N-phenyl)ethenylbenzothiazolium bromide

Rx-ID: 25858210 View in Reaxys 571/630 Yield

Conditions & References 1.A.B : B. To a solution of 3-(2-hydroxy)ethyl-2-methylbenzothiazolium bromide (4a, 1.19 g) in a mixed solvent of methanol/ ethanol (3:1, 80 ml) was added an excess of ethyl N-phenylformimidate (3.0 g) and the solution was stirred at room temperature for 36 h. The solvent was removed under reduced pressure to give a dry solid. The solid was subjected to column chromatography (silica gel, methylene chloride/methanol) purification. The fractions containing the product were combined and concentrated to dryness under reduced pressure. The solid was dissolved in methanol (10 ml) and precipitated with ethyl ether (200 ml). After drying at 50°C under high vacuum overnight, 1.04 g (63percent) of 5a was obtained as a yellow solid. Preparation of 3-(2-Hydroxy)ethyl-6-methyl-2-(2-N-phenyl)ethenylbenzothiazolium Bromide (5b). Patent; Coulter International Corp.; EP1303751; (2005); (B1) English View in Reaxys 3-(2-Hydroary)ethyl-2-(2-N-phenyl)ethenylbenzothiazolium Bromide

Rx-ID: 25858211 View in Reaxys 572/630 Yield

Conditions & References 1.C : Example 1C To a solution of 2,3-dimethylbenzothiazolium bromide (11a, 1.01 g) in ethanol (30 mL) was added excess of ethyl Nphenylformidiate (1.5 g) and stirred at room temperature for 4 days. Evaporated off solvent under reduced pressure to dryness. The solid was subjected to column chromatography (silica gel, methylene chloride/methanol) purification. The fractions contained the product were combined and concentrated to dryness under reduced pressure. The solid was dissolved in methanol (10 mL) and precipitated with ethyl ether (200 mL). After drying in an oven at 50°C under high vacuum overnight there was obtained 0.88 g (60percent) of a yellow solid. TLC (silica gel, 4:1 methylene chloride-methanol) Rf=0.60. Preparation of 3-(2-Hydroary)ethyl-2-(2-N-phenyl)ethenylbenzothiazolium Bromide (12b). Patent; Coulter International Corp.; EP1303751; (2005); (B1) English View in Reaxys 3-(2-Hydroxyethyl)-2-(2-N-phenyl) ethenylbenzothiazolium Bromide

Rx-ID: 25858212 View in Reaxys 573/630 Yield

Conditions & References 1.B.iv : Example 1B (iv) Preparation of 3-(2-Hydroxyethyl)-2-(2-N-phenyl) ethenylbenzothiazolium Bromide (5). To a solution of 3-(2-hydroxyethyl)-2-methylbenzothiazolium bromide (4, 1.19 g) in a mixed solvent of methanol/ethanol (3:1, 80 mL) was added excess of ethyl N-phenylformidiate (3.0 g) and stirred at room temperature for 36 hours. Evaporated off the solvent under reduced pressure to dryness. The solid was subjected to column chromatography (silica gel, methylene chloride/methanol) purification. The fractions contained the product were combined and concentrated to dryness under reduced pressure. The solid was dissolved in methanol (10 mL) and precipitated with ethyl ether (200 mL).

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After drying in an oven at 50°C under high vacuum overnight there was obtained 1.04 g (63percent) of a yellow solid. TLC (silica gel, 9:1 methylene chloride:methanol) Rf= 0.27. Patent; Coulter International Corp.; EP1303751; (2005); (B1) English View in Reaxys

H2N-PEG-NH-CO-NH-Gly-Phe-COOMe

Rx-ID: 27906124 View in Reaxys 574/630 Yield

Conditions & References 4.c : 4.b) 4.c) Removal of Z; synthesis of H2N-PEG-NH-CO-NH-Gly-Phe-COOMe In a 50 ml 3-neck flask, 120 mg of PEG derivative are dissolved in MeOH to which is then added Pd(OH)2 as catalyst in a quantity equal to 20percent by weight on the substrate. The system is left under stirring overnight under H2 atmosphere at room temperature. At the end of the reaction, after removal of the catalyst by filtration through a pleated filter, the MeOH is removed under reduced pressure; the solid obtained is re-dissolved in AcCN and then precipitated from Et2O in an ice-bath, filtered through a Gooch 3G crucible, washed with Et2O and stored over KOH. Patent; Bonora, Gian Maria; Campaner, Pietro; Drioli, Sara; US2008/280998; (2008); (A1) English View in Reaxys

7-ethyl-10-hydroxycamptothecin-(20)-Sar.TFA

Rx-ID: 29293529 View in Reaxys 575/630 Yield

Conditions & References 18 : 7-ethyl-10-hydroxycamptothecin-(20)-Sar.TFA (Compound 20) Example 18 7-ethyl-10-hydroxycamptothecin-(20)-Sar.TFA (Compound 20) Boc-(10)-(7-ethyl-10-hydroxycamptothecin)-(20)-Sar-Boc (compound 19, 900 mg, 1.357 mmol) was added to a solution of 4 mL TFA and 16 mL DCM, and stirred at room temperature for 1 hour. The reaction mixture was evaporated with toluene at 30° C. The residue was dissolved in 10 mL CHCl3 and precipitated with ethyl ether. The product was filtered and dried. Yield 700 mg (1.055 mmol, 78percent). 13C NMR (67.8 MHz, CDCl ) δ 168.26, 167.07, 158.84, 158.71, 148.82, 147.94, 147.22, 146.34, 144.04, 131.18, 3 130.08, 128.97, 124.46, 119.78, 106.02, 97.23, 79.84, 79.34, 66.87, 50.84, 49.86, 31.81, 23.94, 15.47, 13.84, 8.08. Patent; Pastorino, Fabio; Ponzoni, Mirco; US2010/98654; (2010); (A1) English View in Reaxys

O– 2 O

N+

E O

N+

Rx-ID: 10640605 View in Reaxys 576/630 Yield 250 mg 6 (80%)

Conditions & References 3 : Synthesis of 2,6-di[(1E,3E)-4-(4-dimethylaminophenyl)-1,3-butadienyl]-1,3,3,5,7,7-hexamethyl-3,7-dihydropyrrolo[2,3-f]indolediium di(4-methyl-1-benzenesulfonate) (6) EXAMPLE 3 Synthesis of 2,6-di[(1E,3E)-4-(4-dimethylaminophenyl)-1,3-butadienyl]-1,3,3,5,7,7-hexamethyl-3,7-dihydropyrrolo[2,3-f]indolediium di(4-methyl-1-benzenesulfonate) (6) 150 mg (0.86 mmol) of 3-(4-dimethylaminophenyl)acrylaldehyde was dissolved in 5 ml of acetic anhydride, and 209 mg (0.34 mmol) of 1,2,3,3,5,6,7,7-octamethyl-3,7-dihydropyrrolo[2,3-f]indoledinium di-4-methyl-1-benzenesulfonate 3b was added. The mixture was refluxed for 1 hour.

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After cooling the solvent was removed under reduced pressure. The residue was treated with hexane, filtered and washed with hexane and Et2O. The remaining solid was redissolved in a minimum volume of nitromethane and precipitated with Et2O. Yield 250 mg 6 (80percent). UV: λmax (abs) 727 nm (MeOH) λmax (abs) 766 nm (CHCl3), λmax (fl) 810 nm (CHCl3). Very weak fluorescence in CHCl3 and no fluorescence in MeOH. δH (200 MHz, DMSO-d6) 8.34 (2H, t, 14 Hz, CH), 8.24 (2H, s, bispyrrolenin arom. H), 7.78 (2H, d, 14 Hz, CH), 7.61 (4H, d, 7.7 Hz, arom H), 7.47 (4H, d, 7.6 Hz, Tos H), 7.32 (2H, t, 14 Hz, CH), 7.1 (4H, d, 7.6 Hz, Tos H), 6.93 (2H, d, 14 Hz, CH), 6.85 (4H, d, 7.7 Hz, arom H), 3.9 (6H, s, N+CH3), 3.1 (12H, s, NCH3), 2.28 (6H, s, Tos CH3), 1.77 (12H, s, indolenine CH3). Patent; Terpetschnig, Ewald A.; US2007/281363; (2007); (A1) English View in Reaxys 2 N+ E

I–

N+

Rx-ID: 10640608 View in Reaxys 577/630 Yield

Conditions & References

90 mg 12 (60%)

7 : 2,6-di(4-dimethylaminostyryl)-1,3,3,5,7,7-hexamethyl-3,7-dihydropyrrolo[2,3-f]indolediium diiodide (12) EXAMPLE 7 2,6-di(4-dimethylaminostyryl)-1,3,3,5,7,7-hexamethyl-3,7-dihydropyrrolo[2,3-f]indolediium diiodide (12) 60 mg (0.403 mmol) of 4-dimethylaminobenzaldehyde was dissolved in 5 ml of acetic anhydride, and 100 mg (0.191 mmol) of 1,2,3,3,5,6,7,7-octamethyl-3,7-dihydropyrrolo[2,3-f]indoledinium diiodide 3a was added. The mixture was refluxed for 40 min. After cooling the solvent was removed under reduced pressure by a rotary evaporator. The residue was treated by hexane, filtered off and washed with hexane and Et2O. Solid was redissolved in a minimum volume of nitromethane and precipitated with Et2O. Yield 90 mg 12 (60percent). UV: λmax (abs) 649 nm (EtOH), 643 nm (MeOH), 650 nm (CHCl3), λmax (fl) 687 nm (EtOH), λmax (fl) 682 nm (MeOH), λmax (fl) 683 nm (CHCl3); δH (200 MHz, DMSO-d6) 8.34 (2H, d, 15.6 Hz, CH), 8.22 (2H, s, bispyrrolenin arom H), 8.10 (4H, d, 8.5 Hz, arom H), 7.25 (2H, d, 15.6 Hz, CH), 6.93 (4H, d, 8.5 Hz, arom H), 4.01 (6H, s, N+-CH3), 3.18 (12H, s, N(CH3)2), 1.81 (12H, s, 13.4 bispyrrolenin CH3). Patent; Terpetschnig, Ewald A.; US2007/281363; (2007); (A1) English View in Reaxys

OH N

Rx-ID: 10736247 View in Reaxys 578/630 Yield 3.55 g (34%)

Conditions & References 148.A : 4-(2-Fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid cyclopropylmethoxy-amide Step A: Preparation of 4-hydroxy-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester: A mixture of 2-methyl-3-oxo-pentanedioic acid diethyl ester (10.0 g, 46.3 mmol), 1,1-diethoxy-ethene (12.8 mL, 92.5 mmol) and sodium methoxide (0.026 mg, 0.481 mmol) was heated to 85° C. for nine hours. The reaction mixture was cooled to room temperature and concentrated. To the resulting residue was added methylamine (1.91 mL, 55.5 mmol, 40percent H2O). After stirring at room temperature for 16 hours, the reaction mixture was diluted with diethyl ether and washed with water. The aqueous phase was acidified to pH 1 with 10percent HCl solution and extracted with EtOAc. The organic layer was dried (MgSO4) and concentrated. Trituration of the resulting residue with diethyl ether and flash column chromatography (3percent MeOH in methylene chloride) gave 3.55 g (34percent) desired product. Patent; Marlow, Allison L.; Wallace, Eli; Seo, Jeongbeob; Lyssikatos, Joseph P.; Yang, Hong Woon; Blake, James; US2005/256123; (2005); (A1) English

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View in Reaxys

O S NH O

O O

Rx-ID: 23936565 View in Reaxys 579/630 Yield

Conditions & References 96 : Example 96 Example 96 To a mixture of 282 mg of 4-tert.-butyl-N-[6-chloro-5-(p-tolyl)4-pyrimidinyl]-benzene sulfonamide (Example 12c) and 1.10 g of 4-phenoxy-2-butyn-1-ol (prepared starting from phenyl-propargylether and para-formaldehyde following the procedure given in J. Chem. Soc. Perkin Trans. 1, 1991, 1721-1727) in 15 ml THF was added 271 mg of 55percent NaH in mineral oil. The suspension was stirred for 4 h at reflux. The reaction mixture was cooled, diluted with 100 ml 10percent aqueous citric acid and extracted 4 times with 50 ml of ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluding with heptane:ethyl acetate 1:1 and precipitated from diethyl ether to give 151 mg of 4-tert.-butyl-N-[6-(4-phenoxy-2-butynyloxy)-5-(p-tolyl)4-pyrimidinyl]benzene sulfonamide as a white powder. LC-MS: tR=6.34 min, [M+1]+=542.48, [M-1]-=540.15. Patent; Bolli, Martin; Boss, Christoph; Clozel, Martine; Fischli, Walter; US2003/87920; (2003); (A1) English View in Reaxys NH 2 Br

H N

O O N N

NH O

Rx-ID: 23936566 View in Reaxys 580/630 Yield

Conditions & References 4 : (R,S)-4-(4-amino-3,5-dibromophenyl)-2-{{[(1-methyl-4-piperidinyl)oxy]carbonyl}amino}-1-{4-[2(2H)oxo-1,3,4,5-tetrahydro-1,3-benzodiazepin-3-yl]-1-piperidinyl}-1,4-butanedione (I. No. 24) EXAMPLE 4 (R,S)-4-(4-amino-3,5-dibromophenyl)-2-{{[(1-methyl-4-piperidinyl)oxy]carbonyl}amino}-1-{4-[2(2H)-oxo-1,3,4,5-tetrahydro-1,3-benzodiazepin-3-yl]-1-piperidinyl}-1,4-butanedione (I. No. 24) 2.657 ml (0.022 mol) of diphosgene was added dropwise to the suspension of 2.4 g (0.016 Mol) of 1-methyl-4-piperidinol-hydrochloride in 20 ml of acetonitrile, whilst cooling eternally with ice water, the resulting mixture was stirred for 30 minutes at a reaction temperature of 0° C. and overnight at room temperature, whereupon a clear solution was formed which was freed from solvent in vacuo. The residue was triturated with diethylether, suction filtered and dried. This product was added to the mixture of 0.8 g (1.131 mmol) of (R,S)-2-amino-4-(4-amino-3,5-dibromophenyl)-1-{4[2(2H)-oxo-1,3,4,5-tetrahydro-1,3-benzodiazepin-3-yl]-1-piperidinyl}-1,4-butanedione-trifluoroacetate (I. No. 18), 0.175 ml DIEA and 100 ml THF and it was stirred at room temperature until a clear solution had formed. The solvent was eliminated and the residue was added to a mixture of 10 ml of conc. ammonia and 100 ml of water. It was extracted exhaustively with diethylether, the combined ether extracts were dried over sodium sulphate and evaporated down. 0.10 g (12percent of theory) of colourless crystals were obtained,

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Rf=0.27 (FM Q) IR (KBr): 1716, 1655 cm-1 (C=O) ESI-MS: (M-H)-=731/733/735 (Br2); (M+H)+=733/735/737 (Br2) Patent; Rudolf, Klaus; Doods, Henri; Bauer, Eckhart; Hurnaus, Rudolf; Eberlein, Wolfgang; Dreyer, Alexander; Mueller, Stephan Georg; US2003/212057; (2003); (A1) English View in Reaxys O

N N

NH O

S O

Rx-ID: 23936568 View in Reaxys 581/630 Yield

Conditions & References 94 : Example 94 Example 94 To a mixture of 250 mg of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(N-morpholino)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 9c) and 1.2 g of 4-methoxy-2-butyn-1-ol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) was added 192 mg of 55percent NaH in mineral oil. After evolution of gas had ceased, the brown suspension was refluxed for 16 h. Further 96 mg of 55percent NaH in mineral oil was added and heating and stirring was continued for another 3 h. The mixture was cooled, diluted with 50 ml of 10percent aqueous citric acid and extracted 4 times with 50 ml of ethyl acetate. The combined organic phases were washed with water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluding with hexane:ethyl acetate 1:3 and precipitated from diethyl ether to give 114 mg of 5-isopropyl-N-[6-(4-methoxy-2-butynyloxy)-5-(o-methoxyphenoxy)-2(N-morpholino)-4-pyrimidinyl]-2-pyridine sulfonamide as a white powder. LC-MS: tR=5.19 min, [M+1]+=584.46, [M-1]=582.38. Patent; Bolli, Martin; Boss, Christoph; Clozel, Martine; Fischli, Walter; US2003/87920; (2003); (A1) English View in Reaxys F F

O N

O F

Rx-ID: 24006316 View in Reaxys 582/630 Yield 121 mg (59 %)

Conditions & References 14.e : Ether: Evaporation and precipitation from Et2O/pentane gave 121 mg (59 percent) (2S,4R)-Pyrrolidin-1-yl-[2-(2,4,5-trifluorobenzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-methanone, MS: 617 (M+H+). Trityl deprotection (following Method 3) gave (2S,4R)-[4-mercapto-2-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidin-1-yl]pyrrolidin-1-yl-methanone, MS: 374 (M). Patent; Aebi, Johannes; Bur, Daniel; Chucholowski, Alexander; Dehmlow, Henrietta; Kitas, Eric Argirios; Obst, Ulrike; Wessel, Hans Peter; US2002/40146; (2002); (A1) English View in Reaxys

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N O

Rx-ID: 24006317 View in Reaxys 583/630 Yield

Conditions & References 11 : Synthesis of Intermediate F: Synthesis of Intermediate F: 0.7 g (3.34 mmoles) intermediate E 0.389 ml (3.67 mmoles) terbutanol 0.329 ml (3.67 mmoles) perchloric acid 14 ml nitromethane Terbutanol and perchloric acid are added in order to the solution of intermediate E in nitromethane. After 20 hours, the product precipitates by the addition of ethyl ether, and is isolated by filtration. The product is purified by dissolution in acetone and precipitation with ethyl ether. It is filtered and washed several times with ethyl ether. 600 mg of product are thus obtained (yield=49percent). Synthesis of 1-(1,1-dimethylethyl)-3-methyl-4,7-dimethoxy-1H-3H-2,1-benzoxazole 600 mg (1.6 mmoles) intermediate F Patent; ENICHEM S.p.A.; US2002/22724; (2002); (A1) English View in Reaxys

O OH

O N

Cl Cl N

H 2O

Rx-ID: 24075438 View in Reaxys 584/630 Yield

Conditions & References 37 : N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-(2-oxo-1-piperidinyl)-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate (1:1:0.75) Example 37 N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-(2-oxo-1-piperidinyl)-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate (1:1:0.75) Using standard acylation conditions 3-cyano-1-naphthoyl chloride (prepared from 3-cyano-1-naphthoic acid and oxalyl chloride) was reacted with N-[(S)-2-(3,4-dichlorophenyl)-4-[4-(2-oxo-1-piperidinyl)-1-piperidinyl]butyl]-N-methylamine (Miller, S C; WO 9410146). A portion of the product was converted to the citrate salt and isolated by filtration from Et2O to afford the title compound as a white solid. MS: m/z 591 (M+H). Analysis for C33H36Cl2N4O2.C6H8O7.0.75 H2O: calculated: C, 58.76; H, 5.75; N, 7.03. found: C, 58.80; H, 5.63; N, 6.88. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys

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S O

O OH

N OH

O HO

O N

Cl Cl F F

H 2O

Rx-ID: 24075439 View in Reaxys 585/630 Yield

Conditions & References 58 : N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-trifluoromethyl-1-naphthamide Citrate Hydrate Example 58 N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-trifluoromethyl-1-naphthamide Citrate Hydrate Using standard acylation conditions, 3-trifluoromethyl-1-naphthoyl chloride (0.11 g) was reacted with N-[(S)-2-(3,4dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methylamine (0.19 g), converted to the citrate salt and isolated by filtration from diethyl ether to afford the title compound (0.3 g) as an off-white powder. MS APCI, m/z=675 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 11.0 (broad), 8.55-8.40 (m), 8.30-8.10 (m), 7.91-7.63 (m), 7.62-7.45 (m), 7.44-7.12 (m), 7.05-6.85 (m), 3.20-2.76 (m), 2.75-2.55 (m), 2.20-1.65 (m); analysis calculated for C35H35Cl2F3N2O2S, 1 C6H8O7, 1 H2O, C 55.60, H 5.12, N 3.16, found C 55.42, H 5.02, N 3.12. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys

NH 2 N

HO OH

N H

O O

HO N

N N

Rx-ID: 24075440 View in Reaxys 586/630 Yield

Conditions & References 12 : (2R,3R,4S,5R)-2-(6-Amino-2-cyclopentylamino-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol bis(trifluoroacetate) Example 12 (2R,3R,4S,5R)-2-(6-Amino-2-cyclopentylamino-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)-tetrahydro-furan-3,4-diol bis(trifluoroacetate) Intermediate 12 (0.050 g, 0.14 mmol) and cyclopentylamine (0.08 ml, 0.68 mmol) in anhydrous dimethysulfoxide (0.1 ml) was heated at 120° C. for 7 days. A further portion of cyclopentylamine (0.04 ml, 0.34 mmol) with additional dimethylsulfoxide (2 drops) and the reaction mixture was heated at 120° C. for a further 24 h. The reaction mixture was diluted with methanol (3 ml) and purified using preparative HPLC (10-60percent acetonitrile). Solvent was removed in vacuo, the residue azeotroped with methanol and dried in vacuo. After tituration with diethyl ether the title compound was obtained as a pale yellow solid (0.034 g) LC/MS SYSTEM A Rt=3.34 min; LC/MS SYSTEM A m/z 417 (MH+) Patent; Cox, Brian; Keeling, Suzanne Elaine; Allen, David George; Redgrave, Alison Judith; Barker, Michael David; Hobbs, Heather; Roper IV, Thomas Davis; Geden, Joanna Victoria; US2002/86850; (2002); (A1) English

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View in Reaxys N N

Cl HCl

Rx-ID: 24075441 View in Reaxys 587/630 Yield

Conditions & References 1 : 1H-Imidazole, 1-[[1-(3,4-dichlorophenyl)-1H-imidazol-4-yl]methyl]-2-propyl-, Hydrochloride (1:2) EXAMPLE 1 1H-Imidazole, 1-[[1-(3,4-dichlorophenyl)-1H-imidazol-4-yl]methyl]-2-propyl-, Hydrochloride (1:2) Sodium hydride (0.44 g of a 55 O/o dispersion in mineral oil, 10 mmol) was slowly added to a solution of 2-propylimidazole (0.55 g, 5 mmol) in DMF. After 30 min at 20° C. the mixture was cooled in an ice bath and 4-chloromethyl-1-(3,4-dichloro-phenyl)-1H-imidazole (1.0 g, 4 mmol) was added in one portion. The resulting mixture was stirred for 30 min at 20° C. After evaporation of the solvent, the residue was dissolved in AcOEt, washed with H2O, dried (Na2SO4) and chromatographed [silica, elution with gradient CH2Cl2 to 50percent (CH2Cl2/MeOH/aq. NH4OH=90:10:1)]. The free base of the title compound was obtained as a brownish oil (1.12 g, 84percent). After treatment with a solution of HCl in MeOH followed by addition of Et2O the title compound was isolated as a white crystalline material. Mp. 241-243° C. (MeOH/Et2O), MS: m/e=334(M+). Patent; Alanine, Alexander; Buettelmann, Bernd; Heitz Neidhart, Marie-Paule; Jaeschke, Georg; Pinard, Emmanuel; Wyler, Rene; US2002/151715; (2002); (A1) English View in Reaxys N N

Cl HCl

Rx-ID: 24075442 View in Reaxys 588/630 Yield

Conditions & References 108 : 1H-Imidazole, 1-[[1-(3,4-dichlorophenyl)-1H-imidazol-4-yl]methyl]-2,5-dimethyl-, Hydrochloride (1:2) EXAMPLE 108 1H-Imidazole, 1-[[1-(3,4-dichlorophenyl)-1H-imidazol-4-yl]methyl]-2,5-dimethyl-, Hydrochloride (1:2) A suspension of N-[-(3,4-dichloro-phenyl)-1H-imidazol-4-ylmethyl]-thioacetamide (0.60 g, 2.0 mmol) in acetone (10 ml) was treated with K2CO3 (0.28 g, 2.0 mmol) and iodomethane (0.26 g, 1.8 mmol). The mixture was refluxed for 1 h, evaporated and suspended in EtOH (3 ml). After addition of propargylamine (1.1 g, 20 mmol) it was refluxed for 9 h. After filtration and evaporation the residue was purified by chromatography [silica, elution with gradient CH2Cl2 to 30percent (CH2Cl2/MeOH/aq. NH4OH=90:10:1)] and the free base of the title compound (0.20 g, 28percent) was isolated as a light brown oil. After treatment with a solution of HCl in MeOH followed by addition of Et2O the title compound was isolated as a white crystalline material. Mp.>250° C. (MeOH/Et2O), MS: m/e=321 (M+H+). Patent; Alanine, Alexander; Buettelmann, Bernd; Heitz Neidhart, Marie-Paule; Jaeschke, Georg; Pinard, Emmanuel; Wyler, Rene; US2002/151715; (2002); (A1) English View in Reaxys

Cl N

HCl N

Rx-ID: 24075444 View in Reaxys 589/630 Yield

Conditions & References 112 : 1-(3,4-Dichloro-phenyl)-3-(2-methyl-imidazol-1-yl-methyl)-1H-pyrazole Hydrochloride (1:1) EXAMPLE 112 1-(3,4-Dichloro-phenyl)-3-(2-methyl-imidazol-1-yl-methyl)-1H-pyrazole Hydrochloride (1:1)

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A solution of 1-(3,4-dichloro-phenyl)-3-methyl-1H-pyrazole (1.4 g, 6.1 mmol) in carbon tetrachloride was treated with N-bromosuccinimide (1.2g, 6.8 mmol) and a catalytic amount of 2,2'azobis-(isobutyronitrile). The mixture was refluxed for 2 h, cooled, filtered and evaporated. The oily residue was dissolved in DMF (10 ml) and added to a solution of sodium hydride (0.32 g, 7.3 mmol, cf example 1) deprotonated 2-metylimidazole (0.60 g, 7.3 mmol) in DMF (10 ml). After stirring for 12 h at rt all volatiles were removed in vacuo and the residue obtained was dissolved in AcOEt. The organic phase was washed with H2O (3*), dried (Na2SO4) and concentrated. Purification by chromatography [silica, elution with gradient CH2Cl2 to 60percent (CH2Cl2/MeOH/aq. NH4OH=90:10:1)] gave the free base of the title compound (0.98 g, 52percent) as a light brown oil. After treatment with a solution of HCl in MeOH followed by addition of Et2O the title compound was isolated as a white crystalline material. Mp. 204-205° C. (MeOH/Et2O), MS: m/e=306 (M+). Patent; Alanine, Alexander; Buettelmann, Bernd; Heitz Neidhart, Marie-Paule; Jaeschke, Georg; Pinard, Emmanuel; Wyler, Rene; US2002/151715; (2002); (A1) English View in Reaxys

O O

Rx-ID: 24075446 View in Reaxys 590/630 Yield

Conditions & References 1-Methyl-2-(2-nitrophenyl)-benzimidazole-4-carboxaldehyde ethylene acetal (6) 1-Methyl-2-(2-nitrophenyl)-benzimidazole-4-carboxaldehyde ethylene acetal (6) A solution of 2-(2-nitrophenyl)-benzimidazole-4-carboxaldehyde ethylene acetal 5 (4.53 g, 14.6 mmol) in dry THF (20 mL) was added to a stirring suspension of NaH (0.640 g, 60percent dispersion in mineral oil, 16.0 mmol) in dry THF (50 mL) at 0° C. under N2. The mixture was then allowed to warm to room temperature for 1 hour resulting in an orange solution. Methyl iodide (4.58 mL, 72.8 mmol) was syringed into the above mixture at room temperature under N2. This mixture was stirred for 24 hours under N2 to give a yellow mixture. Water was added and the aqueous layer was extracted with CHCl3. The combined extracts were washed with brine and dried over Na2SO4. After rotary evaporation, the resulting residue was purified by column chromatography on silica gel using Et2O:CH2Cl2 (3:1) as the eluent to give the title compound. (3.53 g, 74percent). 1H

NMR (CDCl3): δ 3.58 (s, 3H), 4.02-4.19 (m, 4H), 6.55 (s, 1H), 7.33-7.41 (m, 1H), 7.52-7.56 (m, 1H), 7.62-7.75 (m,

4H), 8.19 (d, J=1.7, 7.9 Hz, 1H); HRMS: Calcd. for C17H15N3O4 325.1062, found 325.1050. Patent; The Ohio State University; US6376664; (2002); (B1) English View in Reaxys

Cl Cl OH OH

O OH

Rx-ID: 24075447 View in Reaxys 591/630 Yield

Conditions & References 8 : N-[2-(S)-(3,4-Dichlorophenyl)-4-[4[(R)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1naphthamide Citrate Hydrate Example 8 N-[2-(S)-(3,4-Dichlorophenyl)-4-[4[(R)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide Citrate Hydrate

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Using standard reductive amination conditions (except that acetic acid-sodium acetate buffer was substituted for acetic acid) N-[(S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-1-naphthamide (468 mg, 1.1 mmol) was reacted with 4-[(R)-2-methylsulfinylphenyl]-piperidine (piperidine (Shenvi, A B; Jacobs, R T; Miller, S C; Ohnmacht. C J Jr; Veale, C A.; WO 9516682) (232 mg, 1.04 mmol), converted to the citrate salt, and isolated by filtration from Et2O to afford the title compound (651.2 mg) as a white powder. MS m/z 632 (M+H); analysis for C35H35Cl2N3O2S.C6H8O7.H2O: calculated: C, 58.43; H, 5.38; N, 4.98; found: C, 58.10; H, 5.20; N. 4.82. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys

S O

O OH

O HO

O N

Cl Cl

N O

Rx-ID: 24075448 View in Reaxys 592/630 Yield

Conditions & References 15 : N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-6-nitro-1naphthamide Citrate Example 15 N-[(S)-2-(3,4-Dichlorophenyl)-4-[4-[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-6-nitro-1-naphthamide Citrate A solution of 6-nitro-1-naphthoic acid (0.2 g, 0.922 mmol) (Dewar, M J S and Grisdale, P J; J. Amer Chem. Soc., 84, 3541 (1962)) in thionyl chloride (2 mL) was heated under reflux for 3 h. The solution was concentrated in vacuo then residual solvent was coevaporated twice with toluene to yield the acid chloride (0.217 g, quantitative) as a off white solid which was used without further purification. Using standard acylation conditions 6-nitro-1-naphthoyl chloride was reacted with N-[(S)-2-(3,4-dichlorophenyl)-4-[4[(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methylamine, converted to the citrate salt, and isolated by filtration from Et2O MS m/z 652 (M+H); analysis for C34H35Cl2N3O4SC6H8O7.H2O: calculated: C, 55.68; H, 5.26; N, 4.87; found: C, 55.78; H, 5.20; N, 4.75. Patent; Astra Zeneca AB; US6365602; (2002); (B1) English View in Reaxys N

NH N

N NH

Cl O

Rx-ID: 24294561 View in Reaxys 593/630 Yield

Conditions & References 44 : 4-(3-Chloro-phenylamino)-3-(4-methoxy-benzylamino)-1H-pyrazolo[3,4-d]-pyrimidine EXAMPLE 44 4-(3-Chloro-phenylamino)-3-(4-methoxy-benzylamino)-1H-pyrazolo[3,4-d]-pyrimidine A mixture of 4.475 g (15 mmol) of 4-cyano-5-(dimethylamino-methyleneamino)-3-(4-methoxy-benzylamino)-pyrazole, 2.83 g (17.25 mmol) of 3-chloro-aniline hydrochloride and 80 ml of ethanol is heated under reflux for 16 hours. Cooling to approx. 5° C., filtering and washing the filter residue with diethyl ether yield the title compound; m.p. 222-223° C.

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The starting material is prepared as follows: Patent; Novartis AG; US5981533; (1999); (A1) English View in Reaxys N

OH NH

NH N

Rx-ID: 24294562 View in Reaxys 594/630 Yield

Conditions & References 59 : 4-(3-Chloro-phenylamino)-3-(3-hydroxy-phenylamino)-1H-pyrazolo[3,4-d]-pyrimidine EXAMPLE 59 4-(3-Chloro-phenylamino)-3-(3-hydroxy-phenylamino)-1H-pyrazolo[3,4-d]-pyrimidine With the exclusion of air and moisture, a mixture of 0.5 g (1.36 mmol) of 4-(3-chloro-phenylamino)-3-(3-methoxyphenylamino)-1H-pyrazolo[3,4-d]pyrimidine (Example 50), 0.873 g (6.55 mmol) of anhydrous aluminum chloride and 15 ml of benzene is heated at 80° C. for 9 hours. The benzene phase is then decanted off, the resinous residue is partitioned between ethyl acetate and water and the organic phase is washed with water and with a saturated solution of sodium hydrogen carbonate in water, dried over sodium sulfate and concentrated by evaporation in vacuo. The residue is purified by flash chromatography on silica gel having a particle size of 0.04-0.06 mm using methylene chloride/methanol mixtures (50:1 and 20:1). The product-containing fractions are combined and concentrated to a volume of approx. 10 ml, the desired product crystallising out. Filtering and washing the filter residue with diethyl ether yield the title compound; m.p. 265-266° C.; EI-MS: (M)+ =352. Patent; Novartis AG; US5981533; (1999); (A1) English View in Reaxys Cl

O NH

N HN

O N

Rx-ID: 24294563 View in Reaxys 595/630 Yield

Conditions & References 63 : 4-(3-Chloro-phenylamino)-3-(4-ethoxy-phenylamino)-1H-pyrazolo[3,4-d]-pyrimidine EXAMPLE 63 4-(3-Chloro-phenylamino)-3-(4-ethoxy-phenylamino)-1H-pyrazolo[3,4-d]-pyrimidine A mixture of 5.8 g (19.44 mmol) of 4-cyano-5-(dimethylamino-methyleneamino)-3-(4-ethoxy-phenylamino)-pyrazole, 3.51 g (21.4 mmol) of 3-chloro-aniline hydrochloride and 40 ml of methanol is heated under reflux for 15 hours. Cooling to 10° C., filtering and washing the filter residue with methanol and diethyl ether yield the title compound; m.p. 232-233° C.; EI-MS: (M)+ =380. Patent; Novartis AG; US5981533; (1999); (A1) English View in Reaxys N

NH N

N NH

NH 2 Cl

Rx-ID: 24294564 View in Reaxys 596/630

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Yield

Conditions & References 38 : EXAMPLE 38 EXAMPLE 38 In the presence of 30 mg of Raney nickel, 110 mg (0.30 mmol) of 3-(3-nitro-phenyl)-4-(3-chloro-phenylamino)-1Hpyrazolo[3,4-d]pyrimidine are hydrogenated in 3 ml of methanol and 3 ml of THF. The catalyst is filtered off, then 15 g of silica gel are added to the filtrate, which is then concentrated by evaporation. Application of the powder to a silica gel column, elution with methylene chloride/ethanol (15:1) and stirring of the crude product with diethyl ether/hexane yield 3-(3-amino-phenyl)-4-(3-chloro-phenylamino)-1H-pyrazolo-[3,4-d]pyrimidine; m.p. 264-266° C.; TLC: Rf =0.45 (methylene chloride/methanol 10:1); HPLC: TRet (Grad20-100)=9.7. Patent; Novartis AG; US5981533; (1999); (A1) English View in Reaxys

OH O

Rx-ID: 24367011 View in Reaxys 597/630 Yield

Conditions & References 16 : 1-carboxymethyl-1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-methyloxime hydrochloride EXAMPLE 16 1-carboxymethyl-1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-methyloxime hydrochloride 3 g of 1-(1,1-dimethylethoxycarbonylmethyl)-1,2,5,6-tetrahydropyridin-3-carboxaldehyde-O-methyloxime is dissolved in 30 cm3 of anhydrous toluene, 2.27 g of paratoluene sulphonic acid is added and the whole is heated to reflux for 1 hour. After evaporating to dryness, the residue is taken up with 1,2-dichloroethane, salified with gaseous hydrochloric acid, and precipitated with anhydrous ethyl ether. By filtering and re-crystallizing from ethanol, 1.8 g of the expected product is obtained. m.p. 213° C., with decomposition). Patent; Roussel UCLAF; US5219872; (1993); (A1) English View in Reaxys O

Cl N O

Rx-ID: 24444170 View in Reaxys 598/630 Yield 1.03 g (1.76 mmole, 44%)

Conditions & References 15.D : Step D A solution of 1.84 g (3.96 mmole) of (S)-1-[N-(3-bromophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid (from Step C) in 15 ml of DMF was cooled over ice, and 2.07 g (16.0 mmole) of N,N-diisopropylethylamine was added, followed by the dropwise addition of 1.08 g (4.92 mmole) of dipentylcarbamoyl chloride (from Example 3, Step A) in 5 ml of DMF over 1 hour. The solution was warmed, and after stirring 16 hours at 25° C., the solution was concentrated in vacuo. The residue was stirred with 50 ml of 1N HCl which was extracted with 2*50 ml of methylene chloride. After concentration in vacuo the residue was mixed with 100 ml of diethyl ether which was extracted with 4*30 ml of 5percent sodium bicarbonate. A tan oil which precipitated was combined with the aqueous solution, and the mixture was acidified to pH 1.0 with 1N HCl. Extraction with 100 ml of chloroform gave 1.03 g (1.76 mmole, 44percent) of tan foam which was homogeneous by TLC (80:80:2 chloroform-methanol-ammonium hydroxide, Rf =0.45). Mass spectrum (FAB): m/e 587 (M+1) 1 H NMR (CDCl3, 400 MHz, ppm): δ0.85 (t, 6H), 1.18 (m, 4H), 1.27 (m, 4H), 1.46 (m, 4H), 2.70 (t of d, 1H), 2.90 (d of d, 1H), 3.10 (m, 5H), 3.26 (d, 1H), 3.61 (d, 1H), 3.94 (d, 1H), 4.71 (s, 1H), 7.05 (d of d, 1H), 7.10-7.26 (m, 6H), 7.33 (t, 2H). Patent; Merck and Co., Inc.; US5348955; (1994); (A1) English View in Reaxys

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H N

O N

Rx-ID: 24461539 View in Reaxys 599/630 Yield

Conditions & References 10 : EXAMPLE 10: The resulting dihydroquinazolone is treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 227 mg, 1.0 mmole) and heating is continued as above for 1 hour. After cooling to room temperature, the precipitated solid is filtered and washed with methanol. The product is recrystallized from methanol to yield a colorless solid. 1 H-NMR (CDCl3) δ:8.54 (d,1H);8.30 (d,1H); 7.77 (m,2H); 7.51-7.43 (m,2H); 7.15 (t,1H); 7.05 (d,1H); 4.30 (q,2H,-CH 2 CH3); 1.60 (t,3H,-CH2 CH3). Patent; Molecular Probes, Inc.; US5316906; (1994); (A1) English View in Reaxys

E O

S HO

Rx-ID: 24461542 View in Reaxys 600/630 Yield

Conditions & References 43 : Preparation of (E,E)-3-(6,6-dimethyl-2-hepten-4-ynyl)-4-[3-[2-[3-(3-thienyl)phenyl]ethenyl]phenyl]-2-butanol EXAMPLE 43 Preparation of (E,E)-3-(6,6-dimethyl-2-hepten-4-ynyl)-4-[3-[2-[3-(3-thienyl)phenyl]ethenyl]phenyl]-2-butanol 44 μl of oxalyl chloride is added dropwise to a mixture of 3.6 μl of dimethyl sulfoxide with 2 μl of methylene chloride under a nitrogen atmosphere and under cooling at -78° C. and stirring, and the mixture is stirred at that temperature for 10 minutes. A methylene chloride solution (0.4 ml) of 105 mg of (E,E)-2-(6,6-dimethyl-2-hepten-4-ynyl)-3-[3-[2-[3-(3-thienyl)phenyl]ethenyl]phenyl]propanol obtained in Example 12 is added dropwise to this solution under cooling at -78° C. and stirring, the mixture is stirred at that temperature for 20 minutes, 200 μl of triethylamine is added, and the mixture is further stirred at -78° C. for 20 minutes. The solvent is distilled off under reduced pressure, the residue is led to two liquid phases using a system of water and ethyl ether, the organic layer is washed with saturated saline and dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. The residue is purified by medium pressure liquid chromatography [column: Lobar column: size A, Lichroprep Si 60F (produced by Merck Co.); eluent: hexane/ethyl acetate=20/1] to obtain 76.6 mg (yield: 73percent) of (E)-2-(6,6-dimethyl-2-hepten-4-ynyl)-3-[3-[2-[3-(3-thienyl)phenyl]ethenyl]phenyl]propionaldehyde as a colorless oily matter. Patent; Banyu Pharmaceutical Co., Ltd.; US5444084; (1995); (A1) English View in Reaxys

H N N

O O

H N

N N

O O

Rx-ID: 24520408 View in Reaxys 601/630 Yield

Conditions & References C : 2-Chloro-4,6-bis (2-[3,4-dimethoxyphenyl]ethylamino)-1,3,5-triazine PREPARATION C 2-Chloro-4,6-bis (2-[3,4-dimethoxyphenyl]ethylamino)-1,3,5-triazine Cyanuric chloride (2.0 g, 10.85 mM) was dispersed in dioxane (80 mL) with stirring and 2-(3,4-dimethoxyphenyl)ethylamine (3.93 g, 21.68 mM) was introduced dropwise over 2 minutes.

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Sodium hydroxide (1N, 24 mL) was added dropwise over 5 minutes then the whole was brought to reflux for 18 hours. Cooling to ambient temperature caused a white solid to precipitate. Diethyl ether (100 mL) was introduced to fully precipitate the product which was filtered, rinsed with diethyl ether and dried. 5.05 g, (98percent), mp=186°-186.5° C. Patent; Pfizer Inc.; US5536722; (1996); (A1) English View in Reaxys

N N

O HO

Rx-ID: 24520410 View in Reaxys 602/630 Yield

Conditions & References 208.c : c c 4'-[(2-Ethyl-4-methyl-6-(1-methyl-5-fluoro-benzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylic Acid A solution of 1.4 g (2.4 mMol) of tert.butyl 4'-[(2-ethyl-4-methyl-6-(1-methyl-5-fluoro-benzimidazol-2-yl)-benzimidazol-1-yl)-methyl]-biphenyl-2-carboxylate and 15 ml of trifluoroacetic acid in 30 ml of methylene chloride is stirred for 14 hours at ambient temperature, then concentrated by evaporation, the residue is mixed with about 30 ml of water and made alkaline with 2N sodium hydroxide solution. After extracting twice with 30 ml of diethyl ether, the aqueous phase is acidified with 20percent citric acid. The crude product precipitated is suction filtered and purified by column chromatography (100 g silica gel; eluant: methylene chloride/ethanol=96:4). Yield: 850 mg (69percent of theory), Melting point: 246°-248° C. Patent; Dr. Karl Thomae GmbH; US5591762; (1997); (A1) English View in Reaxys

O N N N O

Rx-ID: 24596665 View in Reaxys 603/630 Yield

Conditions & References 91 : EXAMPLE 91: Extraction is carried out with 400 cm3 of ethyl ether and the salt is obtained with 4 cm3 of a 10N solution of HCl in isopropanol. 1.25 g (0.00269 mol; yield: 31.4 percent) of a pale yellow powder are obtained. Melting point (dihydrochloride): 210° C. (acetonitrile). IR (KBr ν cm-): 3380(NH+), 2950, 1610, 1575, 1470, 1275, 990, 750. 1H NMR (d6 -DMSO) δ: 8.40-8.28 (m, 2H, H4 H9), 7.75-7.37-7.25 (m, 5H, C6 H4 H3), 6.91-6.78 (m, 2H, H7 H8), 4.85 (m, NH+ +CH2), 4.47 (M, 4H, pip. CH2), 3.95 (s, 3H, CH3), 3.45 (m, 4H, pip. CH2). Patent; Adir Et Compagnie; US5599812; (1997); (A1) English View in Reaxys

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N O NH NH O

Rx-ID: 24666482 View in Reaxys 604/630 Yield

Conditions & References 75.A : EXAMPLE 75 (A) 4-[3-(2-Benzyloxyphenyl)propyl]benzene isocyanate in dioxane (1/3 of the solution that was prepared as described in (B) below) was added to a stirred solution of 2-aminomethylpyridine (0.2 ml) in dichloromethane (10 ml) for 1 hour, evaporated to dryness and subjected to medium pressure chromatography on silica gel to give, after crystallisation from diethyl ether, 1-[4-(3-(2-benzyloxyphenyl)propyl)phenyl]-3-[2-pyridylmethyl]urea (0.62 g) mpt 126°-127° C. Patent; Zeneca Limited; US5811459; (1998); (A1) English View in Reaxys

S O

Rx-ID: 24822628 View in Reaxys 605/630 Yield

Conditions & References S-(1-Phenyl-5-tetrazolyl) chlorothioformate (52) STR76 S-(1-Phenyl-5-tetrazolyl) chlorothioformate (52) STR76 A 20percent phosgene solution in toluene (14.4 ml, 25.2 mmole) was added to a mixture of triethylamine (2.58 ml, 18.5 mmol) and 1-phenyl-1H-tetrazol-5-thiol (3.00 g, 16.8 mmole) in THF (15 ml) at 5° C. over 10 min. The reaction mixture was stirred for an hour at 5° C. and filtered. The filtrate obtained was evaporated and the residue washed thoroughly with ethyl ether. It was then recrystallized by dissolving in THF and precipitating with ethyl ether to give white crystal (2.92 g, 72percent) m.p. 112°-114° C. IR (Film) 1718, 1645, 1590, 1490 and 1395 cm-1. 1 H-NMR (CDCl3) δ7.52 (s, aromatic H). Patent; University of Kentucky Research Foundation; US5008245; (1991); (A1) English View in Reaxys

O OH

Rx-ID: 24904591 View in Reaxys 606/630 Yield

Conditions & References 5.A : A) A) 1-(3-Cyclopentyloxy-4-methoxyphenyl)-3-phenylpropan-1-ol Following the procedure of Example 4A, from magnesium turnings (32.42 mmol, 0.788 g), 2-bromoethylbenzene (32.42 mmol, 6.00 g), 3-cyclopentyloxy-4-methoxybenzaldehyde (32.42 mmol, 7.14 g) of Example 1A, and anhydrous ethyl ether (300 mL) is obtained the title compound as a white solid (29.4 mmol, 9.60 g; 91percent) which is of sufficient purity to be used directly without further purification. NMR (DMSO-d6, 300 MHz) δ7.21 (m, 5H), 6.89 (d, J=2.0 Hz, 1H), 6.87 (d, J=8.5 Hz, 1H), 6.80 (dd, J=8.5; 2.0 Hz, 1H), 5.12 (d, 1H), 4.76 (m, 1H), 4.42 (m, 1H), 3.70 (s, 3H), 2.58 (m, 2H), 2.73 (m, 10H). Patent; American Home Products Corporation; US5124455; (1992); (A1) English View in Reaxys

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Rx-ID: 24984088 View in Reaxys 607/630 Yield 71.8 g (73%)

Conditions & References 1 : Preparation of (d,l)-2-Methoxy-1-[(2-trimethylaminoethoxy)phosphinyloxy]eicosane, hydroxy inner salt Recrystallization from chloroform yielded one-spot material on silica gel; Rf =0.4 (1:1 cyclohexane/ethyl acetate); weight=77.5 g (61.8percent). A reaction mixture, prepared by mixing 77.1 g of the above diol, 735 ml of hexane, 37.6 ml of triethylamine and 68.3 g of trityl chloride, was heated to reflux for about 3 days. It was then cooled, and the hexane removed by evaporation. Equal volumes of chloroform and water were added. The chloroform layer was separated. The aqueous layer was extracted with an equal volume of chloroform, and the two chloroform extracts combined. The combined extracts were dried and the chloroform removed by evaporation. The residue, comprising (d,l)-1-trityloxy-2-hydroxyeicosane formed in the above reaction, was dissolved in n-hexane (60°-68° C.) and the solution cooled. The resulting crystals were separated by filtration and the filtrate evaporated to dryness. Crystallization of the resulting residue from diethylether yielded 71.8 g (73percent) of (d,l)-1-trityloxy-2-hydroxyeicosane; Rf=0.3 (5:1 cyclohexane/ether). Patent; Eli Lilly and Company; US4659859; (1987); (A1) English View in Reaxys

Rx-ID: 25002357 View in Reaxys 608/630 Yield

Conditions & References 8 : 5-(1-Octynyl)furan-2-carboxaldehyde EXAMPLE 8 5-(1-Octynyl)furan-2-carboxaldehyde To a solution of 1-octyne (5.5 g, 50 mmole) in dry THF (40 ml) at -30° C. was added n-butyl lithium in hexane (1.05 eq). After warming to 0° C. over 1 hr a solution of zinc chloride (6.95 g, 50 mmole) in THF (50 ml) was added and temperature raised to room temperature over 1/2 hr. Sequentially, solutions of 5-bromofuran-2-carboxaldehyde (8.75 g, 50 mmole) in THF (20 ml) and tetrakis triphenylphosphinepalladium (0) (5.7 g, 10percent) in THF (50 ml) were added. The mixture was heated to reflux for 2 hr after which it was cooled and added to dilute hydrochloric acid (50 ml). After extracting into diethyl ether (3*100 ml), drying the ethereal solution (MgSO4) and removing the solvent under reduced pressure, the resulting oil was chromatographed on silica (DCM: Hexane 1:2) to give the title compound 6.83 g (67 percent) as an oil. νmax (film) 3150, 3125, 2225, 1680, 890, 770; δ(CDCl3)0.90(3H, distorted t), 1.42(8H, complex m), 2.45(2H, t, J=6.5 Hz), 6.60(1H, d, J=3.0 Hz), 9.65(1H, s). Patent; Beecham Group p.l.c.; US4732901; (1988); (A1) English View in Reaxys NH O

Rx-ID: 25002591 View in Reaxys 609/630 Yield

Conditions & References 3 : Dimethylchloroformamidinium Chloride (6 Mole Scale) EXAMPLE 3 Dimethylchloroformamidinium Chloride (6 Mole Scale)

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A solution of dimethylformamide (448.0 g, 6.28 moles) in anhydrous diethyl ether (12.0 l) was prepared. Patent; McNeilab, Inc.; US4743400; (1988); (A1) English View in Reaxys NH H 2N

S HN

N H

Rx-ID: 25002593 View in Reaxys 610/630 Yield

Conditions & References 3 : N-methansulphonyl-N'-[2-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]ethyl]formamidine The hydrochloride is prepared by dissolving the base in absolute ethanol and adding a stoichiometric quantity of saturated hydrogen chloride solution in ethanol, and the formed hydrochloride precipitates with ethyl ether. Melting point: 110°-112° C. One acid group (anhydrous medium): 96.2percent. IR Spectrum: characteristic bands at 1610 cm-1 (C=N, st). 1 H-NMR (DMSO-d ) δ=2.54 (2H, t, --S--CH --CH ), 2.84 (3H, s, --SO --CH ), 3.4 (2H, m, --CH --CH --NH--), 3.78 6 2 2 2 3 2 2 (2H, s, het--CH2 --S), 7.16 (1H, s, thiazole), 7.98 (1H, d, --NH--CH=N--), 8.32 (4H, wide, guanidine), 8.85 (1H, wide, --NH--CH=). Patent; Ferrer Internacional S.A.; US4728655; (1988); (A1) English View in Reaxys

N F

N Cl O

Rx-ID: 25002595 View in Reaxys 611/630 Yield

Conditions & References 1 : EXAMPLE 1 EXAMPLE 1 This example illustrates the preparation of the compounds of Formula 1 of the invention wherein R2 is a halomethyl. In this example 1-(2-fluorophenyl)-3-methyl-5-(1,2,2,2-tetrachloroethyl)imino-1,3-diazolidine-2,4-dione (7.75 g, 0.02 mol) was dissolved in 20 ml of acetonitrile, 2-fluoro aniline (2.2 g, 0.02 mol) was added. A mild exothermic reaction took place. After 10 minutes, triethylamine was added to the reaction mixture causing a very exothermic reaction to take place. Exothermicity subsided within the hour but stirring was continued for five hours. Ethyl ether (20 ml) was added to help precipitate the salts. The mixture was filtered and solvent was removed from the filtrate by high vacuum evaporation, thereby affording 1(2-fluorophenyl)-3-methyl-5-(1-2'-fluorophenylamino-2,2,2-trichloroethyl)imino-1,3-diazolidine-2,4-dione identified its I.R. and p.m.r. spectera and the elemental analysis. (Anal. calcd. for C18 H13 Cl3 F2 N4 O2; MW=461.69; C, 46.83; H, 2.84; N, 23.04 found; C, 45.6; H, 2.9; N, 22.7). Patent; Chevron Research Company; US4248620; (1981); (A1) English View in Reaxys N Cl

N O

Rx-ID: 25060033 View in Reaxys 612/630 Yield

Conditions & References 7 : 5-Chloro-2-[2-(5-chloropyridin-2-yloxy)phenoxy]-pyrimidine EXAMPLE 7 5-Chloro-2-[2-(5-chloropyridin-2-yloxy)phenoxy]-pyrimidine

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With stirring, 1.80 grams (0.012 mole) of 2,5-dichloropyrimidine was added to a mixture of 2.0 grams (0.009 mole) 2(5-chloropyridin-2-yloxy)phenol, 1.5 grams potassium carbonate, and 40 ml of methyl ethyl ketone. After the addition, the mixture was heated at reflux overnight and then poured into excess H2 O. After extracting with 200 ml of ethyl ether, the extract was washed with saturated NaHCO3, H2 O, brine, dried (MgSO4), filtered, and evaporated to yield a yellow solid which was recrystallized from 1-chlorobutane to give 2.3 grams of product, m.p. 108°-111°; ir (Nujol): 6.35, 6.50 (C=N), 13.20 microns; NMR (CDCl3): δ6.75 (d, 1H, pyridine ring proton), 7.35 (s, 4H, ArH), 7.65 (AB quartet, 1H, pyridine ring proton), 8.10 (d, 1H, pyridine ring proton), 8.55 (s, 2H, pyrimidine ring protons). Patent; E. I. Du Pont de Nemours and Company; US4371736; (1983); (A1) English View in Reaxys Cl Cl

O OH

Rx-ID: 25060034 View in Reaxys 613/630 Yield

Conditions & References 164 : EXAMPLE 164 EXAMPLE 164 To 9.6 g of ethyl[ (6,7-dichloro-2-isobutylbenzo[b]thien-5-yl)oxy]acetate in 75 ml of 95percent ethanol is added 175 ml of a 6 N sodium hydroxide solution and the mixture is refluxed at 100° for 30 mins. The cooled mixture is concentrated in vacuo to give a slurry which is diluted with 500 ml of water and 500 ml of diethyl ether. With stirring and cooling, the mixture is acidified with 6 N hydrochloric acid. The acidic mixture is extracted with diethyl ether. The ether extracts are washed, dried over anhydrous magnesium sulfate, filtered and the solvent is removed. Recrystallization of the solid from diethyl ether and hexane gives 8.3 g of [(6,7-dichloro-2-isobutylbenzo[b]thien-5yl)oxy]acetic acid, mp 164°-165°. ANALYSIS: Calculated for C14 H14 Cl2 O3 S: 50.48percentC, 4.20percentH; Found: 50.41percentC, 4.23percentH. Patent; Hoechst-Roussel Pharmaceuticals Inc.; US4436748; (1984); (A1) English View in Reaxys HN N

HCl

Rx-ID: 25144209 View in Reaxys 614/630 Yield

Conditions & References 1 : 1-[2-(Phenylmethyl)phenyl]piperazine hydrochloride EXAMPLE 1 1-[2-(Phenylmethyl)phenyl]piperazine hydrochloride In a flask fitted with stirrer and cooler, 18.33 g (0.1 mole) of 2-benzylaniline and 17.85 g (0.1 mole) of bis-(2-chloroethylamine)hydrochloride are dissolved in 100 ml of n-butanol and refluxed for 8 hours in an oil bath. The mixture is then allowed to cool, and 6.91 g (0.05 mole) of anhydrous potassium carbonate are added under reflux for 8 hours; the addition of 6.91 g of anhydrous potassium carbonate under 8-hour reflux ws repeated twice. It is then allowed to cool, the insoluble salts are filtered and the butyl alcohol solution is evaporated to dryness in vacuo. The resinous residue is dissolved in 100 ml of methylene chloride, a stream of hydrochloric acid gas with cooling is bubbled into, and the hydrochloride precipitates by adding ethyl ether; it is then filtered and dried to give 28 g of a slightly coloured solid. 10.36 g (37percent) of end product as a whitish solid, m.p. 192°-194° C. were obtained by recrystallization from acetonitrile. IR Spectrum (KBr), cm-1: 3350, 3100-2440, 1490, 1230, 930, 765. 1 H--NMR Spectrum (d -DMSO) ppm: 3.1 (two symmetric bands, 8H; piperazine), 4.0 (s, 2H; Ar--CH --Ar), 7.2 (m, 6 2 9H, Ar--) and 9.8 (wide, 2H; --N+ H2).

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Patent; Ferrer Internacional S.A.; US4859675; (1989); (A1) English View in Reaxys

N O

N H

Rx-ID: 25147482 View in Reaxys 615/630 Yield

Conditions & References SYNTHESIS OF N-BUTYRYL-N'-CINNAMYL-2,6-DIMETHYL-PIPERAZINE HYDROCHLORIDE SYNTHESIS OF N-BUTYRYL-N'-CINNAMYL-2,6-DIMETHYL-PIPERAZINE HYDROCHLORIDE 37.4 g (0.2M) of 2,6-dimethyl-piperazine dihydrochloride suspended in 200 ml of isopropanol are fed into a 500 ml three-neck flask fitted with a magnetic agitator, a bulb-type reflux condenser with a CaCl2 plug, a thermometer and a dropping funnel, and 23.5 g (0.2M) of 97percent 2,6-dimethyl-piperazine are added under strong agitation. The mixture is left under agitation at ambient temperature until complete dissolution has taken place. Dissolving time about 90 minutes. It is heated to 65° C. and 32 g (0.2M) of 95percent cinnamyl chloride dissolved in 50 ml of isopropanol are dripped in under strong agitation. Addition time about 20 minutes. When the addition is complete, the mixture is left under agitation for 45 minutes at 65° C. and then for 12 hours at ambient temperature. In this manner a slurry is obtained which is filtered under vacuum. The solid residue consists of 32 g of 2,6-dimethyl-piperazine dihydrochloride. The filtrate is evaporated to dryness under low pressure and taken up in 150 ml of benzene and 150 ml of water and acidified to pH 1.5 with concentrated HCl. It is left under agitation for 15 minutes, after which the phases are separated. The aqueous phase is adjusted to pH 11 with 10percent NaOH and extracted three times with 150 ml of benzene. The pooled organic phases are dried with anhydrous sodium sulphate and filtered. 18.2 g (25 ml, 0.18M) of triethylamine are added to the clear solution obtained, and then 18.1 g (0.17M) of butyryl chloride are dripped in under strong agitation while maintaining the reaction temperature at 25° C. Addition time about 15 minutes. The mixture is left under agitation at ambient temperature for 12 hours, after which 100 ml of cold water are added, and the mixture acidified to pH 1.5 with concentrated HCl. In this manner a rubbery precipitate is obtained which is filtered off, washed with 50 ml of benzene and dried at 50° C. under vacuum. 30 g of product are obtained of 94percent purity. The product is dissolved in 100 ml of acetonitrile, filtered over carbon and precipitated with 150 ml of ethyl ether. In this manner 21 g of product are obtained having the following characteristics: Patent; Euroresearch S.R.L.; US4562191; (1985); (A1) English View in Reaxys

S O

H N

O F

F F

Rx-ID: 25147484 View in Reaxys 616/630 Yield

Conditions & References A : Preparation of isopropyl 2-[[[4-(trifluoromethoxy)phenyl]amino]thio]benzoate The resulting diethyl ether solution was dried using magnesium sulphate and evaporated to yield the crude product which was purified by crystallisation from diethyl ether/light petroluem. The crystallisation yielded 7.4 g of the desired product as colourless plates, melting point 120°-121° C. The following analytical results were obtained: Calculated: C: 55.0percent, H: 4.3percent, N: 3.8percent. Found: C: 55.0percent, H: 4.5percent, N: 3.8percent. Patent; Shell Oil Company; US4517193; (1985); (A1) English

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View in Reaxys

Rx-ID: 25212199 View in Reaxys 617/630 Yield

Conditions & References 1 : EXAMPLE 1 EXAMPLE 1 Acrylic chloride (5 grams, 0.055 mole) was added drop by drop and under continuous agitation to a solution of C6 F13 --C2 H4 --NH--CH2 CH2 OH (21 grams, 0.052 mole) and triethylamine (5 grams, 0.05 mole) in methylene chloride (60 cm3), cooling the reaction vessel with an ice-water bath. After the reaction, the precipitated triethylamine chlorhydrate was filtered and ethyl ether was added to the filtrate to precipitate the triethylamine chlorhydrate remaining in solution in the methylene chloride. After filtration, the solvents were eliminated by prolonged evaporation under vaccuum. The viscous residual liquid (20 grams), which was difficult to purify, was made up of STR16 containing C6 F13 C2 H4 NHC2 H4 OCOCH=CH2 as an impurity. Patent; Produits Chimiques Ugine Kuhlmann; US3997604; (1976); (A1) English View in Reaxys

O O

Rx-ID: 25212259 View in Reaxys 618/630 Yield

Conditions & References 7 : EXAMPLE 7 EXAMPLE 7 To a mixture of 26 parts of 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline and 11 parts of triethylamine in 220 parts of benzene is added portionwise, at room temperature over a 40 minute period, 160 parts of a benzene solution containing 20 parts of phosgene. After the addition is complete, the reaction mixture is stirred at room temperature for an additional 90 minutes, then is heated up to reflux for 30 minutes and filtered. The filtrate is evaporated to afford a residual solid, ethyl ether is added and the mixture filtered. The solid thus obtained is 6,7-dimethoxy-1-phenyl-3,4-dihydro-2(1H)-isoquinolinecarbonyl chloride, melting at about 151°-152°C. Patent; G. D. Searle and Co.; US4001244; (1977); (A1) English View in Reaxys

O N

Rx-ID: 25212262 View in Reaxys 619/630 Yield

Conditions & References 10 : 2-Phenyl-3-[3-(hexamethylenimino)propionyl]-5-methylbenzofuran. EXAMPLE 10 2-Phenyl-3-[3-(hexamethylenimino)propionyl]-5-methylbenzofuran. A mixture of 21.3 grams of 2-phenyl-3-acetyl-5-methylbenzofuran, 3.9 grams of paraformaldehyde, 17.4 grams of hexamethylenimine hydrochloride, 80 milliliters of isopropanol and 8 milliliters of a saturated solution of hydrogen

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chloride in ethanol was heated under reflux for a period of 8 hours, after which the solvent was evaporated therefrom under vacuum. The residue consisted of a crystalline mass of the hydrochloride of the compound named in the heading of this example. The crystalline mass was triturated with a small quantity of water and then dried on a suction filter. The dried crystals were redissolved in ethanol and precipitated by addition of ethyl ether to the solution in ethanol. In this manner, 22.1 grams of the hydrochloride, having a melting point of 143.5°-145.5° C, was obtained. Patent; Kali-Chemie Aktiengesellschaft; US4009184; (1977); (A1) English View in Reaxys

HCl N

Rx-ID: 25283370 View in Reaxys 620/630 Yield

Conditions & References 9.B : B. B. 1,2,3,6-Tetrahydro-1-[3-(3-indenyl)propyl]-4-methylpyridine, hydrochloride A solution of 135 g (0.409 mole) of the compound formed in part A above in 200 ml of water and 120 ml of methanol is cooled to 15°. Over a period of 30 minutes, 16 g (0.424 mole) of sodium borohydride is added. The mixture is stirred for 2 hours at room temperature, acidified with glacial acetic acid, and then basified with potassium carbonate. It is extracted with a total of 1200 ml of ethyl ether (containing 200 ml of chloroform) and 600 ml of chloroform. All organic extracts are combined, dried and evaporated in vacuo to give 129 g of an orange-brown liquid. A chloroform solution of this material is extracted with 1 liter of 7percent hydrochloric acid which is separated, basified and extracted with ether. The ether extract is dried and evaporated to give 19 g of black sludge which is discarded. The original chloroform layer is evaporated in vacuo to give 140 g of dense oil whose IR spectrum indicates that it is a hydrochloride salt. This material is slurried with ether, basified and the ether layer dried and evaporated to give 82 g of mobile oil which is distilled in vacuo to give, after a forerun of 5.7 g, bp 130-151° at 0.4 mm, 41.3 g of oil, bp 146-156° at 0.4 mm. Patent; E. R. Squibb and Sons, Inc.; US4053596; (1977); (A1) English View in Reaxys

OH O N O Se

Se O N O OH

Rx-ID: 25283371 View in Reaxys 621/630 Yield

Conditions & References 4.b : 1,1'-[Diselenobis(3-oxo-3,1-propanediyl)]bis-L-proline (b) To 30 ml. of the diselenide solution obtained in part (a) (nitrogen atmosphere) there is added at once a solution of 5.7 g. of 1-(3-bromo-1-oxopropyl)-L-proline which has been neutralized with potassium carbonate (about 20 ml. of final solution). The mixture becomes slightly exothermic. After one hour of stirring at room temperature, the yellow-brown solution is cooled and acidified with 10percent potassium bisulfate.

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The product is extracted with 3*50 ml. of ethyl acetate. Evaporation of the dried extract (MgSO4) yields 4 g. of yellow glassy oil. The oil is dissolved in chloroform and precipitated with ethyl ether. Cooling of this precipitate to 0° furnishes an amorphous, slightly yellow solid which turns oily at room temperature. The precipitation is repeated to yield, after drying in vacuo at 40°-45°, analytically pure product, 1,1'-[diselenobis(3oxo-3,1-propanediyl)]bis-L-proline, as yellow foam. Anal. Calc'd for C16 H24 N2 O6 Se2. H2 O: C, 37.21; H, 5.07; N, 5.43 C, 37.45; H, 4.75; N, 5.35. Patent; E. R. Squibb and Sons, Inc.; US4181663; (1980); (A1) English View in Reaxys

O HO

H N

N O

Rx-ID: 25355465 View in Reaxys 622/630 Yield

Conditions & References R.B.121 : Production of N-[6-[3-[4-(diphenylmethoxy)piperidino]-propylamino][1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl]-2,2-dimethylglycine ethyl ester fumarate Reference Example B121 Production of N-[6-[3-[4-(diphenylmethoxy)piperidino]-propylamino][1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl]-2,2-dimethylglycine ethyl ester fumarate 4-(Diphenylmethoxy)-1-piperidinepropanamine (1.56 g) and N-(6-chloro[1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl)-2,2-dimethylglycine ethyl ester (1.50 g) were dissolved in N,N-dimethylformamide (20 ml); N-ethyldiisopropylamine (1.65 ml) was added, followed by stirring at 70°C for 16 hours. After cooling, aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with ethyl acetate; the extract was washed with brine and dried over magnesium sulfate. The extract was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (50:5:1). The desired fractions were collected and concentrated; the oil obtained (880 mg) was dissolved in ethanol (5 ml), followed by the addition of fumaric acid (170 mg) and concentration; the resulting residue was powdered by the addition of ethyl ether, washed with ethyl ether, collected by filtration and dried to give the title compound (931 mg). Amorphous elemental analysis for C37H45N7O8*H2O*0.5Et2O Calculated (percent): C,60.76; H,6.80; N,12.72 Found (percent): C,60.71; H,6.85; N,12.34 Patent; Takeda Chemical Industries, Ltd.; EP1243271; (2002); (A1) English View in Reaxys

F O

Rx-ID: 25360608 View in Reaxys 623/630 Yield

Conditions & References 1.h : h. h. 2-Cyanoethyl 4-(3-cyanophenyl)-2-trifluoromethyl-5-oxo- 1,4,5,6,7,8-hexahydroquinoline-3-carboxylate. A mixture of 2-cyanoethyl 4-(3-cyanophenyl)-2--trifluoromethyl-2-hydroxy-5-oxo-1,2,3,4,5,6,7,8-octahydroquinoline-3 -carboxylate (4.14g 9.6 mmol), p-toluenesulfonic acid (0.61g 3.2 mmol) and toluene (100 mL) was stirred at reflux under a Dean-Stark apparatus for 2 hours. The reaction mixture, which consisted of dark oil and toluene phases, was cooled and poured on a 1.5 inch diameter chromatography column containing 90g of silica gel. The mixture was washed on the column with a little ethyl acetate.

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Elution with ethyl ether and trituration of the resulting solid with ethyl ether yielded the ester as a yellow-orange solid (2.84g, 72percent); mp 148-151.5 °C; NMR:: 1.79-1.99 (m, 2H, CH2) 2.19-2.33 (m, 2H, CH2) 2.50-2.74 (m, 2H, CH2) 2.85 (t, 2H, CH2) 4.15-4.27 (m, 2H, CH2) 4.94 (s, 1H, CH) 7.47-7.63 (m, 3H, Ar) 7.65-7.67 (m, 1H, Ar) 9.84 (s, 1H, NH); MS: m/z=416(M+1). Analysis for C21H16F3N3O3: Calculated: C, 60.72; H, 3.88; N, 10.12; Found: C, 60.63; H, 3.80; N, 9.89. Patent; AstraZeneca AB; EP755382; (2001); (B1) English View in Reaxys O

H N Cl

Rx-ID: 25414449 View in Reaxys 624/630 Yield

Conditions & References 3.a : a) a) 5,6-dimethoxy-2[[2-(4-benzyloxyphenyl)-2-oxo-1-methylethyl]amino]-1,2,3,4-tetrahydronaphthalene hydrochloride. A solution containing 20.0 g (0.082 mol.) of 5,6-dimethoxy-2-aminotetrahydronaphthalene (IV; R1=H), 26.2 g (0.082 mol.) of 2-bromo(4 benzyloxy)-1-propiophenone (V) and 9.1 g (0.09 mol.) of triethylamine in 82 ml of 95percent absolute ethanol is refluxed with stirring, under nitrogen atmosphere, for 6 hours. At the end of the reaction, the solution is evaporated under vacuum, the resulting residue is taken up into 500 ml of ethyl ether, under stirring. The resulting solid is filtered, taken up into 500 ml of a 15percent K2CO3 aqueous solution and extracted with ethyl acetate (3 x 300 ml). Patent; CHIESI FARMACEUTICI S.p.A.; EP405344; (1991); (A2) English View in Reaxys

O Cl

H H HO

NH 2

Rx-ID: 25414453 View in Reaxys 625/630 Yield 1.00 g (100%)

Conditions & References 34.A : A. A. (3β,5β,14β,17β)-14-Amino-3-hydroxyandrostane-17-carboxylic Acid, Methyl Ester Hydrochloride (3β,5β,14β,17β)-14-Amino-3-hydroxyandrostane-17-carboxylic Acid, Methyl Ester, prepared according to the procedure described in U.S. Pat. No. 4,885,280, incorporated by reference herein, (0.90 g, 0.0026 mol) is dissolved in methanol (5 ml). Methanolic hydrochloric acid is added dropwise to acidify to a pH of 1 and the solution is stirred at ambient temperature for 10 min. The solution is concentrated under reduced pressure to an oil. Trituration of the oil with anhydrous ethyl ether forms a solid which is collected by filtration and air dried yielding 1.00 g (100percent) of the hydrochloride salt. This compound is carried on to the next step. Patent; The Procter and Gamble Company; US5922703; (1999); (A1) English View in Reaxys

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HN O

Rx-ID: 29144170 View in Reaxys 626/630 Yield

Conditions & References 29 : [(3-Cyclohexylaminomethyl-naphthalen-2-ylcarbamoyl)-naphthalen-1-yl-methyl]-phosphonic acid, Cpd 70 Example 29 [(3-Cyclohexylaminomethyl-naphthalen-2-ylcarbamoyl)-naphthalen-1-yl-methyl]-phosphonic acid, Cpd 70 To a stirred solution of Compound 28a (0.125 g, 0.263 mmol) and cyclohexyl amine (0.031 g, 0.316 mmol) in DCE (4 mL) was added NaB(OAc)3H (0.111 g, 0.526 mmol) and glacial acetic acid (0.017 g, 0.316 mmol) and the mixture was stirred for 48 h. The reaction was treated with 3N NaOH, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3*) and the combined organic extracts were washed with water, dried (Na2SO4), filtered (Celite), and concentrated under reduced pressure at rt. The residue was treated with 1N HCl (aq), and the solid was collected, rinsed with water, and air-dried. The product was dissolved in CH3CN, precipitated with Et2O, and the solid was collected and rinsed with Et2O to yield 0.084 g of Compound 29a: HPLC: 3.27 min; MS (ES) m/z 559 (MH+). Patent; Hawkins, Michael J.; Greco, Michael N.; Powell, Eugene; Garavilla, Lawrence de; Maryanoff, Bruce E.; US2010/48513; (2010); (A1) English View in Reaxys

H N

N N

Rx-ID: 29961282 View in Reaxys 627/630 Yield

Conditions & References 12 : Conjugation of Glucosamine and Zidovudine onto H-(Ptyn)4(EOZ)20-T-CO2H D(+)-glucosamine hydrochloride (0.137 g, 0.0663 mmol) was dissolved in 2 mL of 0.1 N boric acid solution followed by the adjustment of pH to 8.5 using 0.1 N NaOH solution. H-(Ptyn)4(EOZ)20-T-SPA (0.19 g, 0.0663 mmol, Mn 3000 Da) was added as a solid. The mixture was stirred for 3 hours at room temperature while maintaining pH at 8.5 using 0.1 N NaOH. The mixture was acidified (pH ~3) and extracted with dichloromethane. The combined organic phases were dried over anhydrous Na2SO4, filtered, concentrated, and dried in vacuo to give 0.14 g of pale yellow powder. The conjugation of glucosamine was confirmed by 1H NMR (Varian, 500 MHz, 10 mg/mL DMSO-d6) that shows the 2-position proton on glucoseamide at 4.92 ppm (s, 1H). Ion exchange chromatography showed a substitution yield of 83percent. H-(Ptyn)4(EOZ)20-T-Gluco (0.05 g, 0.0156 mmol, Mn 3200 Da) and the antiviral nucleoside zidovudine (AZT, 0.0167 g, 0.0625 mmol, 4 eq) were dissolved in water (2 mL). Sodium ascorbate (0.0012 g, 0.00625 mmol) and CuSO4.5H2O (0.0008 g, 0.00313 mmol) were added at room temperature. After stirring for 18 hours, water was removed using a rotary evaporator. The residue was dissolved in a 1:1 mixture of MeOH and CHCl3 and then precipitated by addition to diethyl ether. Diethyl ether solution was decanted and the residue was dried in vacuo to give the desired product as a white powder in a quantitative yield. The 'click' coupling of the azide group on zidovudine to each acetylene pendant on the polymer chain was verified by NMR. 1H NMR (Varian, 500 MHz, 10 mg/mL DMSO-d6) shows that the polymer chain contained an average of >=3.5 units of thymidines with the thymidyl proton peaks at 11.3 ppm (br s, 1H, -OH), 8.05 ppm (s, 1H, triazole), 7.81 ppm (s, 1H), 6.41 ppm (t, 1H), 5.31 ppm (m, 1H), 5.26 ppm (m, 1H), 4.18 ppm (br s, 1H), and 1.80 (s, 3H).

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The 2-position proton on glucoseamide shows at 4.92 ppm (s, 1H). GPC gave Mn=4700 Da and Mp=4830 Da with PDI of 1.07. Patent; Serina Therapeutics, Inc.; US2010/330023; (2010); (A1) English View in Reaxys O O

O O

Rx-ID: 29961283 View in Reaxys 628/630 Yield

Conditions & References 12 : Conjugation of Glucosamine and Zidovudine onto H-(Ptyn)4(EOZ)20-T-CO2H Example 12 Conjugation of Glucosamine and Zidovudine onto H-(Ptyn)4(EOZ)20-T-CO2H After drying azeotropically with acetonitrile, H-(Ptyn)4(EOZ)20-T-CO2H (0.18 g, 0.0619 mmol, Mn 2100 Da by MALDI) was dissolved in dichloromethane (2 mL). NHS (0.0071 g, 0.0619 mmol) and DCC (0.0128 g, 0.0619 mmol) were added at room temperature. After stirring overnight at room temperature, the mixture was filtered and precipitated by addition to diethyl ether. Diethyl ether solution was decanted and the residue was dried in vacuo to give the desired N-hydroxysuccinimide ester; i.e. H-(Ptyn)4(EOZ)20-T-SPA as a white powder in a quantitative yield. GFC shows >=95percent purity and attachment of NHS was proved by 1H NMR showing the succinimidyl protons at 2.86 ppm (s, 4H). Patent; Serina Therapeutics, Inc.; US2010/330023; (2010); (A1) English View in Reaxys

O Z

Rx-ID: 8154652 View in Reaxys 629/630 Yield

Conditions & References With 1-methyl-4-isopropenyl-3-benzylidene-cyclohexen-(6)-one-(2), n-propyl-magnesium bromide Maxim; Zugravescu; Teodorescu; ; vol. &lt;2&gt; 3; (1941); p. 24,28; ; (1944); p. 5496 View in Reaxys

C4 buten species O

Rx-ID: 23598936 View in Reaxys 630/630 Yield

Conditions & References The catalyst employed was 12-tungstosilicic heteropolyacid supported on Grace 57 silica with a catalyst loading of 140 grams per litre. The experiment involved start-up and initial operation within standard parameters, described herein as feed 1, until stable baseline activity and impurity make rates were obtained. The reactor feed conditions were then altered by adjusting recycle compressor and pump flow rates. The reaction temperature was increased to maintain the catalyst productivity of ethyl acetate. The process variable alterations were made in parallel, but incrementally to avoid excessive process upset. A summary of the key process variables and experimental data obtained is given in Tables 1 and 2. TABLE 1 - Experimental conditions Feed 1 Feed 2 Feed 3 Reaction pressure Bar (abs) 12 12 12 Ethylene : acetic acid Molpercent/Molpercent 12.2:1 8.2:1 6.6: 1 Etliyleiie water MolpercentIN4olpercent 17:1 11.0:1 8.5:1 Acetic acid : water Molpercent/Molpercent 1.40:1 1.33:1 1.29:1 Recycle rate 26.0 21.0 17.2 Recycle gas purity percent v/v C2- 90.0 90:0 90.0 Reactor inlet temperature °C 175 178 182 (averaged Flash separation °C 30 30 30 temperature TABLE 2 - Experimental results Product/Impurities________Feed] 1 Feed 2 Feed 3 Ethyl acetate STY g/litre cat/hr 200 200 200 2-butanone ppm 43 27 12 Acetaldehyde ppm 200 132 60 Diethylether ppm 20365

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18640 11800 C4 Butene species ppm 520 317 125 (total) Hexane ppm 21 21 16 As can be noted from Table 1, the effect of decreasing ethylene to water ratio over the experimental range requires increased reactor inlet temperatures to maintain a steady ethyl acetate STY. From Table 2, it is shown that, even at these elevated temperatures, the catalyst selectivity is improved, on moving firstly from feed 1 to feed 2 and then to feed 3 compositions. This is clearly illustrated in the given examples by significant reductions to 2-butanone, acetaldehyde, and diethylether production. Similar reduction trends are also observed for C4 and the attendant derivative C6 to C20 hydrocarbon species as illustrated by hexane in the Example. This increased selectivity may also be represented as a function of water partial pressure in Figure 2. The reductions in acetaldehyde and 2-butanone for example enable extended catalyst life as these materials have previously been identified as playing a role in catalyst deactivation. The broad reduction in derivative hydrocarbon species will also confer prolonged catalyst life by removing a source of coking materials for the catalyst surface that would otherwise form a barrier between the reactants and the catalyst active sites. Further economic benefit is realised by optimising feed composition to enable the reduction or elimination of various process purge streams which may be otherwise employed to prevent recycle of components detrimental to catalyst life, as otherwise valuable recyclable materials and feedstock are also inevitably removed along with the undesirable components. A further, advantage is given by the reduced requirement to remove these impurities, thereby allowing an effective de-bottleneck of the process product purification system. , Kinetics Patent; BP CHEMICALS LIMITED; WO2005/110966; (2005); (A1) English View in Reaxys

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