1.1 Piperidine by Asch

Reaxys

PubChem

eMolecules

Reactions (526)

Yield

Substances (1)

Citations (573)

Conditions

References

Synthesize Find similar

Rx-ID: 22294 Find similar reactions

100%

With 5 Ru/MgO; hydrogen in tetrahydrofuran

T=150°C; P=38002.6 Torr; 0.4 h;

Fang, Minfeng; Sanchez-Delgado, Roberto A.

Journal of Catalysis, 2014 , vol. 311, p. 357 - 368 Title/Abstract Full Text View citing articles Show Details

97.9%

With hydrogen; platinum in water

T=149.9°C; P=3750.3 Torr; various pressure, temperature; Mechanism;

Sokol'skii; Dembitskii; Ualikhanova

Journal of applied chemistry of the USSR, 1985 , vol. 58, # 2 pt 2 p. 278 - 281 Title/Abstract Full Text View citing articles Show Details

96%

With samarium diiodide in tetrahydrofuran; water

0.141667 h; Ambient temperature;

Kamochi, Yasuko; Kudo, Tadahiro

Heterocycles, 1993 , vol. 36, # 10 p. 2383 - 2396 Title/Abstract Full Text View citing articles Show Details

96%

With samarium diiodide in tetrahydrofuran; water

0.141667 h; Ambient temperatureother pyridine derivatives, var. amt. of reagents, and time; MechanismProduct distribution;

Kamochi, Yasuko; Kudo, Tadahiro

Heterocycles, 1993 , vol. 36, # 10 p. 2383 - 2396 Title/Abstract Full Text View citing articles Show Details

94%

With hydrogenchloride; samarium

0.166667 h; Ambient temperatureother substituted pyridines, quinolines and isoquinolines; var. metals; Product distribution;

Kamochi; Kudo

Chemical and Pharmaceutical Bulletin, 1995 , vol. 43, # 8 p. 1422 - 1424 Title/Abstract Full Text View citing articles Show Details

90%

With Rh; hydrogen; 1-butyl-3-methylimidazolium Tetrafluoroborate

T=80°C; P=22502.3 Torr; 15 h; Autoclave; chemoselective reaction;

Karakulina, Alena; Gopakumar, Aswin; Akçok, Ismail; Roulier, Bastien L.; LaGrange, Thomas; Katsyuba, Sergey A.; Das, Shoubhik; Dyson, Paul J.

Angewandte Chemie - International Edition, 2016 , vol. 55, # 1 p. 292 - 296 Angew. Chem., 2016 Title/Abstract Full Text View citing articles Show Details

88%

With isopropyl alcohol; nickel

12 h; Heating;

Srivastava, S.; Minore, J.; Cheung, C. K.; Noble, W. J. le

Journal of Organic Chemistry, 1985 , vol. 50, # 3 p. 394 - 396 Title/Abstract Full Text View citing articles Show Details

87.4%

With hydrogen; nickel in water

T=149.9°C; P=3750.3 Torr; effect of further hydrogen pressures, temperatures, ΔE(excit.); Product distributionKineticsThermodynamic data;

Sokol'skii, D. V.; Dembitskii, A. A.; Ualikhanova, A.

Russian Journal of Physical Chemistry, 1985 , vol. 59, # 10 p. 1581 - 1582 Zhurnal Fizicheskoi Khimii, 1985 , vol. 59, # 10 p. 2636 - 2637 Title/Abstract Full Text Show Details

80%

With nickel(II) oxide; hydrogen; palladium in hexane

T=150°C; P=37503.8 Torr; 24 h;

Wang, Yanan; Cui, Xinjiang; Deng, Youquan; Shi, Feng

RSC Advances, 2014 , vol. 4, # 6 p. 2729 - 2732 Title/Abstract Full Text View citing articles Show Details

With hydrogenchloride; tin

Koenigs

Chemische Berichte, 1881 , vol. 14, p. 1856 Full Text Show Details

With ethanol; sodium

Ladenburg,A.; Roth

Chemische Berichte, 1884 , vol. 17, p. 513 Full Text Show Details

Ladenburg,A.

Justus Liebigs Annalen der Chemie, 1888 , vol. 247, p. 51 Full Text Show Details

Ladenburg,A.

Chemische Berichte, 1884 , vol. 17, p. 156 Full Text Show Details

With sulfuric acid; water

bei der elektrolytischen Reduktion an einer Blei- oder QuecksilberKathode;

Ahrens

Zeitschrift fuer Elektrochemie und Angewandte Physikalische Chemie, 1895 , vol. 2, p. 577 Chem. Zentralbl., 1896 , vol. 67, # I p. 1126 Full Text Show Details

Tafel

Zeitschrift fuer Physikalische Chemie, Stoechiometrie und Verwandtschaftslehre, 1900 , vol. 34, p. 220 Full Text Show Details

Pinkussohn

Zeitschrift fuer Anorganische und Allgemeine Chemie, 1897 , vol. 14, p. 395 Full Text Show Details

Merck

Chem. Zentralbl., 1899 , vol. 70, # II p. 982 Full Text Show Details

Merck

Patent: DE104664 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 5, p. 797 Full Text Show Details

Merck

Chem. Zentralbl., 1897 , vol. 68, # I p. 728 Full Text Show Details

Merck

Patent: DE90308 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 4, p. 1239 Full Text Show Details

With acetic acid; platinum

Hydrogenation;

Skita; Meyer

Chemische Berichte, 1912 , vol. 45, p. 3592 Full Text Show Details

With hydrogenchloride; water; platinum

Hydrogenation;

Skita; Brunner

Chemische Berichte, 1916 , vol. 49, p. 1601

Full Text Show Details

With sulfuric acid; water

bei der elektrolytischen Reduktion an einer Thallium-Kathode;

Zerbes

Zeitschrift fuer Elektrochemie und Angewandte Physikalische Chemie, 1912 , vol. 18, p. 624 Full Text Show Details

With platinum

Hydrogenation;

Hamilton; Adams

Journal of the American Chemical Society, 1928 , vol. 50, p. 2260,2263 Full Text Show Details

Zelinsky; Borisow

Chemische Berichte, 1924 , vol. 57, p. 151 Full Text Show Details

Ssadikow; Michailow

Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1926 , vol. 58, p. 532,533, 534 Full Text Show Details

With palladium asbestos

T=150°C;

Zelinsky; Borisow

Chemische Berichte, 1924 , vol. 57, p. 151 Full Text Show Details

With iridium asbestos

T=150°C; Hydrogenation;

Zelinsky; Borisow

Chemische Berichte, 1924 , vol. 57, p. 151 Full Text Show Details

With osmium asbestos

T=150°C; Hydrogenation;

Zelinsky; Borisow

Chemische Berichte, 1924 , vol. 57, p. 151 Full Text Show Details

T=250°C; Hydrogenation.unter Druck;

Ssadikow; Michailow

Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1926 , vol. 58, p. 532,533, 534 Full Text Show Details

With sulfuric acid

bei der elektrochemischen Reduktion an einer Blei-Kathode;

Marie; Lejeune

Journal de Chimie Physique et de Physico-Chimie Biologique, 1925 , vol. 22, p. 59 Full Text Show Details

Bayer and Co

Chem. Zentralbl., 1921 , vol. 92, # II p. 560 Full Text Show Details

Bayer and Co.

Patent: DE310023 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 13, p. 71 Full Text Show Details

T=160°C; P=76000 - 114000 Torr; Hydrogenation.an Nickel auf Traegersubstanzen;

Goodyear Tire and Rubber Co

Chem. Zentralbl., 1933 , vol. 104, # II p. 3917 Full Text Show Details

Goodyear Tire and Rubber Co.

Patent: GB395231 ; Full Text Show Details

Schering-Kahlbaum A.G

Chem. Zentralbl., 1931 , vol. 102, # II p. 314 Full Text Show Details

Schering-Kahlbaum A.G.

Patent: GB346222 ; Full Text Show Details

T=130 - 180°C; P=30400 - 45600 Torr; Hydrogenation.an Nickel auf Traegersubstanzen;

I.G. Farbenindustrie

Chem. Zentralbl., 1933 , vol. 104, # I p. 3788 Full Text Show Details

I.G. Farbenind.

Patent: DE574137 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 18, p. 635 Full Text Show Details

T=175 - 225°C; P=57000 Torr; Hydrogenation.an chromhaltigen Nickel-Katalysatoren;

Du Pont de Nemours and Co

Chem. Zentralbl., 1936 , vol. 107, # I p. 2831 Full Text Show Details

Du Pont de Nemours and Co.

Patent: US2018620 ; Full Text Show Details

Du Pont de Nemours and Co.

Patent: US2019419 ; Full Text Show Details

With nickel

T=200°C; P=110326 - 220652 Torr; Hydrogenation;

Adkins et al.

Journal of the American Chemical Society, 1934 , vol. 56, p. 2425,2427 Full Text Show Details

With silica gel; nickel; palladium

T=130 - 150°C; Hydrogenation;

Uschakow et al.

Bulletin de la Societe Chimique de France, 1935 , vol. <5> 2, p. 573 Full Text Show Details

Uschakow et al.

Zhurnal Obshchei Khimii, 1935 , vol. 5, p. 993 Full Text Show Details

With sulfuric acid; water

bei der elektrochemischen Reduktion an einer Blei-Kathode;

Drosdow

Zhurnal Obshchei Khimii, 1933 , vol. 3, p. 351,353 Chem. Zentralbl., 1934 , vol. 105, # II p. 443 Full Text View citing articles Show Details

Parkes

Patent: US1947732 , 1933 ; Full Text Show Details

With ethanol; hydrogen; sodium

T=130°C;

Am. Hyalsol Corp.

Patent: US1971743 , 1930 ;

With ammonium chloride; ammonia; sodium

T=-80 - -50°C;

Schlubach; Miedel

Chemische Berichte, 1924 , vol. 57, p. 1685 Full Text Show Details

T=180°C; P=25080 Torr; Hydrogenation.an aktivierten NickelSpaenen;

Technical Research Works

Chem. Zentralbl., 1929 , vol. 100, # II p. 797 Full Text Show Details

Technical Research Works

Patent: GB309300 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 19, p. 814 Full Text Show Details

Technical Research Works

Patent: DE558566 ;

Full Text Show Details

H. Th. Boehme A.G.

Patent: DE577037 , 1929 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 19, p. 815 Full Text Show Details

Full Text Show Details

Electrolysis;

Marie; Lejeune

Journal de Chimie Physique et de Physico-Chimie Biologique, 1925 , vol. 22, p. 59 Full Text Show Details

BAYER and Co

Chem. Zentralbl., 1921 , vol. 92, # II p. 560 Full Text Show Details

BAYER and Co.

Patent: DE310023 ; Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 13, p. 71 Full Text Show Details

Davies; McGee

Journal of the Chemical Society, 1950 , p. 678 Full Text Show Details

100 % Chromat.

With hydrogen; rhodium in methanol; water

T=45°C; Atmospheric pressure. Number of molecules of the substrate converted per metal atom per hour (Table 3). Other

Karakhanov, E. A.; Loktev, A. S.; Pshezhetskii, V. S.; Stepanova, I. P.; Dedov, A. G.

Chemistry of Heterocyclic Compounds (New York, NY, United States), 1984 , vol. 20, # 8 p. 835 - 837 Khimiya Geterotsiklicheskikh Soedinenii, 1984 , vol. 20, # 8 p. 1032 - 1034

temperatures. Aq. isopropanol. Rh on a copolymer of styrene with maleic acid.; Product distribution;

Title/Abstract Full Text View citing articles Show Details

With Ni(100) in gas T=6.9 - 376.9°C; other mono and dimethyl substituted derivatives, other products; Product distribution;

Schoofs; Benziger

Journal of physical chemistry, 1988 , vol. 92, # 3 p. 741 - 750 Title/Abstract Full Text View citing articles Show Details

With hydrogen; Ni2P supported on mesoporous silica SBA-15 T=319.84°C; P=15001.5 Torr; Kinetics; Further Variations:Catalysts;

Koranyi, Tamas I.; Vit, Zdenek; Poduval, Dilip G.; Ryoo, Ryong; Kim, Hei Seung; Hensen, Emiel J.M.

Journal of Catalysis, 2008 , vol. 253, # 1 p. 119 - 131 Title/Abstract Full Text View citing articles Show Details

76 %Spectr.

With 5 Rh/C; hydrogen in hexane

T=70°C; P=7600.51 Torr; 12 h; Autoclave;

Motoyama, Yukihiro; Takasaki, Mikihiro; Yoon, Seong-Ho; Mochida, Isao; Nagashima, Hideo

Organic Letters, 2009 , vol. 11, # 21 p. 5042 - 5045 Title/Abstract Full Text View citing articles Show Details

100 %Chromat.

With hydrogen in methanol

T=20°C; P=760.051 Torr; 14 h;

Falini, Giuseppe; Gualandi, Andrea; Savoia, Diego

Synthesis, 2009 , # 14 art. no. Z02609SS, p. 2440 - 2446 Title/Abstract Full Text View citing articles Show Details

100 %Chromat.

With RhCl[2,6-bis{1-(4trifluoromethylphenyl)iminoethyl}pyridine]; potassium tertbutylate; hydrogen in isopropyl alcohol

T=60°C; P=760.051 Torr; 1.08333 h;

Buil, Maria L.; Esteruelas, Miguel A.; Niembro, Sandra; Olivan, Montserrat; Orzechowski, Lars; Pelayo, Cristina; Vallribera, Adelina

Organometallics, 2010 , vol. 29, # 19 p. 4375 - 4383 Title/Abstract Full Text View citing articles Show Details

With hydrogen in water

T=20°C; P=22502.3 Torr; 3 h; Autoclave;

Hubert, Claudie; Bile, Elodie Guyonnet; Denicourt-Nowicki, Audrey; Roucoux, Alain

Green Chemistry, 2011 , vol. 13, # 7 p. 1766 - 1771 Title/Abstract Full Text View citing articles Show Details

With hydrogen in tetrahydrofuran

T=120°C; P=7500.75 Torr; 1 h;

Fang, Minfeng; MacHalaba, Nataliya; Sanchez-Delgado, Roberto A.

Dalton Transactions, 2011 , vol. 40, # 40 p. 10621 - 10632 Title/Abstract Full Text View citing articles Show Details

With hydrogen in isopropyl alcohol

T=60°C; P=760.051 Torr; Catalytic behavior; Reagent/catalyst;

Niembro, Sandra; Donnici, Silvia; Shafir, Alexandr; Vallribera, Adelina; Buil, María L.; Esteruelas, Miguel A.; Larramona, Carmen

New Journal of Chemistry, 2013 , vol. 37, # 2 p. 278 - 282 Title/Abstract Full Text View citing articles Show Details

With hydrogen in ethanol

T=100°C; P=22502.3 Torr; Autoclave; Reagent/catalyst;

He, Teng; Liu, Lin; Wu, Guotao; Chen, Ping

Journal of Materials Chemistry A, 2015 , vol. 3, # 31 p. 16235 - 16241 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 173071 Find similar reactions

90%

With tris(triphenylphosphine)ruthenium(II) chloride in diphenylether

T=180°C; 5 h;

Bui-The-Khai; Concilio, Carlo; Porzi, Gianni

Journal of Organic Chemistry, 1981 , vol. 46, # 8 p. 1759 - 1760 Title/Abstract Full Text View citing articles Show Details

With nitrogen; silica gel

T=400°C;

ICI

Patent: US2863872 , 1954 ;

Full Text Show Details

With hydrogenchloride

bei der trocknen Destillation;

Ladenburg

Chemische Berichte, 1886 , vol. 19, p. 782 Full Text Show Details

Ladenburg,A.

Justus Liebigs Annalen der Chemie, 1888 , vol. 247, p. 51 Full Text Show Details

Ladenburg,A.

Chemische Berichte, 1885 , vol. 18, p. 3101 Full Text Show Details

Ladenburg

Chemische Berichte, 1885 , vol. 18, p. 2957 Chemische Berichte, 1886 , vol. 19, p. 780 Full Text Show Details

Hide Details

33 % Chromat.

With Pt on TiO2 in water

20 h; Ambient temperature;

Nishimoto, Sei-ichi; Ohtani, Bunsho; Yoshikawa, Tadao; Kagiya, Tsutomu

Journal of the American Chemical Society, 1983 , vol. 105, # 24 p. 7180 - 7182 Title/Abstract Full Text View citing articles Show Details

86 % Chromat.

in water

T=300°C; 15 h; other temp.; Rate constant;

Smith, John R. Lindsay; Smart, Alison U.; Twigg, Martyn V.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1992 , # 6 p. 939 - 947 Title/Abstract Full Text Show Details

With 5 wt ruthenium/carbon; aluminium in water

T=158°C; 2 h;

Gaedda, Thomas M.; Yu, Xiao-Yan; Miyazawa, Akira

Tetrahedron, 2010 , vol. 66, # 6 p. 1249 - 1253 Title/Abstract Full Text View citing articles Show Details

T=350°C; P=760.051 Torr; 1 h; Inert atmosphereFlow reactor; Hide Experimental Procedure

Nagashima, Sayoko; Sasaki, Tomoaki; Kamiguchi, Satoshi; Chihara, Teiji

Chemistry Letters, 2015 , vol. 44, # 6 p. 764 - 766 Title/Abstract Full Text View citing articles Show Details

1.2. Catalytic Measurements

General procedure: The reactions were performed in a conventional continuous flow microreactor operated at atmospheric pressure.23 In a typical experiment, a weighed sample (10.0 mg) of 1 or supported 1 on silica gel (1/SiO2) was packed into a borosilicate glass tube (3 mm id), which was placed in the center of an electric furnace. The catalyst sample was initially heated to 350 °C for 1 h in a helium stream (600 mL h–1) for activation, and then reactant was introduced at 350 °C into the stream usinga syringe pump (0.50 mmol h–1). The reaction was monitored by sampling the reaction gas (1 ml) every 30 min using a six-way valve and analyzing the collected gas using an on-line gas–liquid chromatography (GLC). The products were identified by GLC, nuclear magnetic resonance spectrometry, and mass spectrometry by comparison with authentic samples. Conversion =products/(products + recovered reactant) 100percent; selectivity = product/(total amount of products) 100percent. For the measurement of a typical reaction profile (Figure S1), effect of temperature (Figure 1), and reactivities of various halide cluster catalysts (Table S1), the amount of 1,4-butanediol was increased (1.50 mmol h–1) to reduce the conversion. Reactants were diluted with water (for alcohols) or tetrahydrofuran (for non-alcohols) to almost-saturated solutions or lowviscosity liquids at ambient temperature for introduction where necessary.

With putrescine transaminase gene from escherichia coli K12; sodium tris(acetoxy)borohydride in aq. buffer pH=8; Enzymatic reaction; Reagent/catalyst;

Synthesize Find similar

Slabu, Iustina; Galman, James L.; Weise, Nicholas J.; Lloyd, Richard C.; Turner, Nicholas J.

ChemCatChem, 2016 , vol. 8, # 6 p. 1038 - 1042 Title/Abstract Full Text View citing articles Show Details

92%

With trans-carbonyldihydrido(bis(2(diisopropylphosphanyl)ethyl)amine)osmium

T=200°C; 30 h;

Synthesize Find similar

Rx-ID: 214476 Find similar reactions

Bertoli, Marcello; Choualeb, Aldjia; Lough, Alan J.; Moore, Brandon; Spasyuk, Denis; Gusev, Dmitry G.

Organometallics, 2011 , vol. 30, # 13 p. 3479 - 3482 Title/Abstract Full Text View citing articles Show Details

With aluminum oxide

T=300°C;

Scriabine

Bulletin de la Societe Chimique de France, 1947 , p. 454 Full Text Show Details

89 % Chromat.

in neat (no solvent) T=155°C; 24 h;

Murahashi, Shun-Ichi; Kondo, Kaoru; Hakata, Toshiyuki

Tetrahedron Letters, 1982 , vol. 23, # 2 p. 229 - 232 Title/Abstract Full Text View citing articles Show Details

Hide Details

75 % Chromat.

in water

T=300°C; 15 h; other temp.; Rate constant;

Smith, John R. Lindsay; Smart, Alison U.; Twigg, Martyn V.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1992 , # 6 p. 939 - 947 Title/Abstract Full Text Show Details

With Ru3(CO)12; water; N-phenyl-2(dicyclohexylphosphino)pyrrol in cyclohexane

T=140°C; 21 h; Inert atmosphereSchlenk techniqueAutoclave;

Pingen, Dennis; Vogt, Dieter

Catalysis Science and Technology, 2014 , vol. 4, # 1 p. 47 - 52 Title/Abstract Full Text View citing articles Show Details

T=350°C; P=760.051 Torr; 1 h; Inert atmosphereFlow reactor; Hide Experimental Procedure

Nagashima, Sayoko; Sasaki, Tomoaki; Kamiguchi, Satoshi; Chihara, Teiji

Chemistry Letters, 2015 , vol. 44, # 6 p. 764 - 766 Title/Abstract Full Text View citing articles Show Details

1.2. Catalytic Measurements

With silica gel

T=325°C; Inert atmosphere; Reagent/catalyst;

Synthesize Find similar

Ohta, Kaishu; Yamada, Yasuhiro; Sato, Satoshi

Applied Catalysis A: General, 2016 , vol. 517, p. 73 - 80 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 4664678 Find similar reactions

95%

With methanesulfonic acid; ruthenium(1,1,1-tris(di(3,5dimethylphenyl)phosphinomethyl)ethane)(η4trimethylenemethane); hydrogen in tetrahydrofuran

T=160°C; P=75007.5 Torr; 16 h; AutoclaveSchlenk technique;

Meuresch, Markus; Westhues, Stefan; Leitner, Walter; Klankermayer, Jürgen

Angewandte Chemie - International Edition, 2016 , vol. 55, # 4 p. 1392 - 1395 Angew. Chem., 2016 , vol. 128, # 4 p. 1414 - 1417,4 Title/Abstract Full Text View citing articles Show Details

91%

With hydrogen; hexarhodium hexadecacarbonyl; Re2(CO)10 in DME

T=180°C; P=76000 Torr; 16 h;

Hirosawa, Chitaru; Wakasa, Noriko; Fuchikami, Takamasa

Tetrahedron Letters, 1996 , vol. 37, # 37 p. 6749 - 6752 Title/Abstract Full Text View citing articles Show Details

90%

With C18H32ClIrO2P2; tris(pentafluorophenyl)borate; hydrogen; sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate in toluene

T=120°C; P=38002.6 Torr; 24 h; chemoselective reaction;

Yuan, Ming-Lei; Xie, Jian-Hua; Zhu, Shou-Fei; Zhou, Qi-Lin

ACS Catalysis, 2016 , vol. 6, # 6 p. 3665 - 3669 Title/Abstract Full Text View citing articles Show Details

Hide Details

86%

Stage #1: With dimethyl sulfate

T=80°C; 3 h; Inert atmosphere; Stage #2: With platinum on carbon; hydrogen in methanol

T=25°C; P=30003 Torr; 5 h; Reagent/catalystTemperatureTime; Hide Experimental Procedure

Title/Abstract Full Text Show Details

Piperidone-2 (5 g, 50 mmol) is admixed with dimethyl sulphate (5 ml, 50 mmol) and stirred under argon for 3 hours at 80° C., and the product is then taken up in 10 ml of absolute methanol. An autoclave is charged with 5percent Pt/C (0.98 g, 0.5 mol percent), flushed with argon and filled with the reaction solution in methanol. 40 bar of hydrogen are then injected in, and the mixture is stirred at 25° C. and a constant pressure until hydrogen absorption is no longer evident (5 h). After separation off from the catalyst, the filtrate is concentrated on a rotary evaporator, the residue is dissolved in 20 ml of water and washed with diethyl ether, the aqueous phase is rendered basic with 2N NaOH solution and etherified out. The organic phase is dried over K2CO3; after evaporating off the ether virtually clean piperidine is obtained. (0177) The yield can be found in Table 4.

With hydrogenchloride; BH3*Et2NPh

1.) THF, 8 h, reflux; Yield given. Multistep reaction;

Salunkhe, Ashok M.; Burkhardt, Elizabeth R.

Tetrahedron Letters, 1997 , vol. 38, # 9 p. 1519 - 1522 Title/Abstract Full Text View citing articles Show Details

62 % Turnov.

With sodium tetrahydroborate; lithium chloride in diethylene glycol dimethyl ether

T=162°C; 1.5 h;

Zhu, Hua-Jie; Lu, Kai-Tao; Sun, Guang-Ri; He, Jin-Bao; Li, Hai-Qing; Pittman Jr., Charles U.

New Journal of Chemistry, 2003 , vol. 27, # 2 p. 409 - 413 Title/Abstract Full Text View citing articles Show Details

With hydrogen in DME

T=160°C; P=22502.3 Torr; 20 h; Inert atmosphereAutoclaveMolecular sieve;

Stein, Mario; Breit, Bernhard

Angewandte Chemie - International Edition, 2013 , vol. 52, # 8 p. 2231 - 2234 Title/Abstract Full Text View citing articles Show Details

78 %Spectr.

With sodium 2-methyl-2adamantoxide; dichlorobis(dicyclohexylphosphinomethylpyridine)– ruthenium (II); hydrogen; sodium hydride in toluene; mineral oil

T=160°C; P=60006 Torr; 48 h; Inert atmosphereAutoclave; Hide Experimental Procedure

Miura, Takashi; Held, Ingmar E.; Oishi, Shunsuke; Naruto, Masayuki; Saito, Susumu

Tetrahedron Letters, 2013 , vol. 54, # 21 p. 2674 - 2678 Title/Abstract Full Text View citing articles Show Details

Representative procedure for hydrogenation of amides with (RUPCY/base = 1/10):The reaction of N-benzylbenzamide (3a) (conditions A Table 1,entry 1): no preactivation of catalyst.

General procedure: Under a continuous Ar flow, 2-methyl-2-adamantanol (16.6 mg, 0.1 mmol), NaH (60percent oil dispersion, 4.0 mg, 0.1 mmol), anhydrous toluene (1.5 mL) and a magnetic stirring bar were placed in a dried Teflon tube (21 mL capacity). The Teflon tube was stoppered with a rubber septum, and the mixture was stirred at room temperature for 2 h under Ar. After removing the septum, under a continuous Ar flow, to the mixture was added RUPCY (7.50 mg, 0.01 mmol) and N-benzylbenzamide (105.6 mg, 0.5 mmol). The Teflon tube was quickly inserted into an autoclave and the inside of the autoclave was purged several times with hydrogen gas (>5 MPa). The autoclave was pressurized with an 8 MPa of hydrogen gas at 25°C, and heated at 160°C for 24 h under stirring (800 rpm). The autoclave was cooled to room temperature in an ice–water (0°C) bath,and the reaction mixture was quenched with NH4Cl (5.3 mg, 0.1 mmol). The organic phase was removed in vacuo (ca. 100 mmHg, 40 °C). The residue was diluted with CDCl3, and analyzed by 1H NMR. The yields of benzyl alcohol (92percent) and benzylamine (92percent) were calculated based on the integral ratio among the signals of these compounds with respect to an internal standard (1,1,2,2-tetrachloroethane). Afterward, the reaction mixture was purified by column chromatography on silica gel (silica gel (ca. 100 g) was pretreated with Et3N (small amount)–Et2O/hexane (vol percent: 2/3), eluent; Et2O/hexane = 2/3, then EtOAc/Et3N = 100/1) to give N-benzylbenzamide (7.7 mg, 0.036 mmol, 7percent), benzyl alcohol (47.4 mg, 0.438 mmol, 88percent) and benzylamine (44.1 mg, 0.4187 mmol, 82percent).

Synthesize Find similar

Evonik Degussa GmbH; Kadyrov, Renat

Patent: US2016/272571 A1, 2016 ; Location in patent: Paragraph 0176-0177 ;

Synthesize Find similar

Multi-step reaction with 2 steps 1: methanesulfonic acid / [D3]acetonitrile / 24 h / 20 °C / |Molecular sieve 2: methanesulfonic acid / [D3]acetonitrile / 24 h / 20 °C / |Molecular sieve View Scheme

Rx-ID: 41773779 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar Rx-ID: 41773944 Find similar reactions

Synthesize Find similar

Rx-ID: 41773945 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774002 Find similar reactions

Synthesize Find similar

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Synthesize Find similar

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774004 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774005 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774006 Find similar reactions

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774007 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774008 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Synthesize Find similar

Synthesize Find similar Rx-ID: 41774010 Find similar reactions

With methanesulfonic acid in [D3]acetonitrile

T=20°C; 24 h; Molecular sieve; Equilibrium constant;

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Multi-step reaction with 3 steps 1: methanesulfonic acid / [D3]acetonitrile / 24 h / 20 °C / |Molecular sieve 2: methanesulfonic acid / [D3]acetonitrile / 24 h / 20 °C / |Molecular sieve 3: methanesulfonic acid / [D3]acetonitrile / 24 h / 20 °C / |Molecular sieve View Scheme

Rx-ID: 41774053 Find similar reactions

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

Journal of the American Chemical Society, 2016 , vol. 138, # 1 p. 381 - 389 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 42031341 Find similar reactions

A: 87% B: 13%

With water in aq. phosphate buffer

T=25°C; pH=2.7 - 3.2; 1.5 h; Electrochemical reaction; Hide Experimental Procedure

Xu, Yinghua; Ma, Hongxing; Ge, Tingjie; Chu, Youqun; Ma, Chun-An

Electrochemistry Communications, 2016 , vol. 66, p. 16 - 20 Title/Abstract Full Text View citing articles Show Details

General procedure: A conventional two compartment glass or PTFE H-cell separated by a Nafion-117 membrane was used for electrochemical HDF experiments. The cathode was fabricated from a piece of Rh/Ni foam, Rh/Agmesh, Rh/Cu foam, or Rh/carbon felt (projected area: 2 × 3 cm2), whereas the anode was fashioned from a graphite sheet (2 × 3 cm2). 30 mL phosphate buffer solutions (20 mM) served as both the catholyte and the anolyte. Unless otherwise noted, the catholyte was stirred with a stirring velocity of 350 rpm during electrolysis. The concentrations of reactants and their products were determined by an Agilent 7890 A gas chromatograph (GC) and a Waters HPLC system, using standard calibration curves. The fluoride ion (F−) concentration was determined by a REX PHSJ-4F pH/mV meter combined with F− selective electrode (REXPF-202-C). The specific electric energy consumption (SEEC, kW h m−3catholyte) of the HDF process was calculated from the following equation: SEEC I *U*t/1000*V where I is the applied current (A), U is the average cell voltage (3 V), t is HDF time (h), and V is the volume of the catholyte (3 × 10−5 m3). Unless otherwise noted, all of the above-mentioned experimentswere performed under air atmosphere, at 25°C.

Synthesize

Find similar

100%

Find similar

With water in aq. phosphate buffer

T=25°C; pH=2.7 - 3.2; 7.5 h; Electrochemical reaction; Hide Experimental Procedure

Rx-ID: 42031342 Find similar reactions

Xu, Yinghua; Ma, Hongxing; Ge, Tingjie; Chu, Youqun; Ma, Chun-An

Electrochemistry Communications, 2016 , vol. 66, p. 16 - 20 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 42177795 Find similar reactions

With Sc1.5Yb0.5O3

T=425°C; Inert atmosphere;

Ohta, Kaishu; Yamada, Yasuhiro; Sato, Satoshi

Applied Catalysis A: General, 2016 , vol. 517, p. 73 - 80 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 42177796 Find similar reactions

With praseodymium oxide

T=425°C; Inert atmosphere; Reagent/catalystTemperature;

Ohta, Kaishu; Yamada, Yasuhiro; Sato, Satoshi

Applied Catalysis A: General, 2016 , vol. 517, p. 73 - 80 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 42355589 Find similar reactions

A: 15% B: 80%

With sodium tetrahydroborate; hydrogen; nickel dichloride in tertbutyl alcohol

T=70°C; P=760.051 Torr; 10 h; Hide Experimental Procedure

Synthesize Find similar

Mokhov; Popov; Shcherbakova

Russian Journal of General Chemistry, 2016 , vol. 86, # 2 p. 273 - 280 Zh. Obshch. Khim., 2016 , vol. 86, # 2 p. 245 - 252,8 Title/Abstract Full Text View citing articles Show Details

Hydrogenation of 2-piperidino-2-cyanopropane 1j

Hydrogenation of 2-piperidino-2-cyanopropane 1j was performed similarly, using sodium borohydride (0.2 g, 0.005 mol), 15 mL of tert-butanol, anhydrous nickel(II) chloride (0.32 g, 0.0025 mol), and nitrile 1j (3 g, 0.02 mol). The reaction time duration 10 h, the temperature was 70°C. Piperidine 9j, content 15 wt percent. Mass spectrum, m/e (Irel, percent): 85.8 (9) [M+1], 84.8 (22) [M], 83.9 (100), 69.9 (7.4), 56.9 (13.4), 56.0 (48), 44.0 (15.6), 42.0 (20), 40.0 (27.7). 2-Isopropylpiperidine 8j, content 80 wt percent. Mass spectrum, m/e (Irel, percent): 127.9 (2) [M+1], 126.7 (3) [M], 125.8 (4), 112.9 (7.5), 111.9 (100), 84.1 (6), 69.0 (4), 56.2 (10.4), 41.0 (9). A

Synthesize Find similar

B: 97%

With dipotassium peroxodisulfate; tris(2,2'-bipyridyl)ruthenium dichloride in water; acetonitrile

T=20°C; 12 h; Irradiation; Hide Experimental Procedure

Rx-ID: 43894901 Find similar reactions

Chung-Ang University Academic Cooperation; Jo, Uhn Jin; Nadim, Iqbal

Patent: KR101609985 B1, 2016 ; Location in patent: Paragraph 0091; 0092; 0097; 0098; 0099 ; Title/Abstract Full Text Show Details

Example 22:Examples 17 to 24

General procedure: The reaction was carried out substantially the same as the preparation of Example 3 except that the amine compound was changedAnd the results are shown in Table 3 Photocatalyst (Ru (bpy) 3Cl2) was prepared in the amine-based compound, a 1 molpercentconcentration of the oxidizing agent (K2S2O8) and solvent (0.1 M, CH3CN / H2O (1/1))under the condition, the blue light-emitting diode in the power consumption 7W was a12-hour reaction at room temperature using. With the selected amine compound wasanalyzed and the manufactured product are shown in Table 2 below Yield of the product was measured by gas chromatography using a dodecane (dodecane)as an internal standard method A

Synthesize Find similar

B: 90%

Synthesize Find similar

With dipotassium peroxodisulfate; tris(2,2'-bipyridyl)ruthenium dichloride in water; acetonitrile

T=20°C; 12 h; Irradiation; Hide Experimental Procedure

Rx-ID: 43894902 Find similar reactions

Chung-Ang University Academic Cooperation; Jo, Uhn Jin; Nadim, Iqbal

Patent: KR101609985 B1, 2016 ; Location in patent: Paragraph 0091; 0092; 0097; 0098; 0099 ; Title/Abstract Full Text Show Details

Example 23:Examples 17 to 24

Synthesize Find similar

B: 91%

With dipotassium peroxodisulfate; tris(2,2'-bipyridyl)ruthenium dichloride in water; acetonitrile

T=20°C; 12 h; Irradiation; Hide Experimental Procedure

Rx-ID: 43894954 Find similar reactions

Chung-Ang University Academic Cooperation; Jo, Uhn Jin; Nadim, Iqbal

Patent: KR101609985 B1, 2016 ; Location in patent: Paragraph 0091; 0092; 0097; 0098; 0099 ; Title/Abstract Full Text Show Details

Example 19:Examples 17 to 24

Synthesize Find similar

B: 77%

With dipotassium peroxodisulfate; tris(2,2'-bipyridyl)ruthenium dichloride in water; acetonitrile

T=20°C; 12 h; Irradiation; Hide Experimental Procedure

Rx-ID: 43894957 Find similar reactions

Chung-Ang University Academic Cooperation; Jo, Uhn Jin; Nadim, Iqbal

Patent: KR101609985 B1, 2016 ; Location in patent: Paragraph 0091; 0092; 0097; 0098; 0099 ; Title/Abstract Full Text Show Details

Example 24:Examples 17 to 24

wasanalyzed and the manufactured product are shown in Table 2 below Yield of the product was measured by gas chromatography using a dodecane (dodecane)as an internal standard method

Synthesize Find similar

84%

Synthesize Find similar

With platinum on carbon; hydrogen in methanol

T=25°C; P=30003 Torr; 16 h; Autoclave; Hide Experimental Procedure

Rx-ID: 44530684 Find similar reactions

Evonik Degussa GmbH; Kadyrov, Renat

Patent: US2016/264513 A1, 2016 ; Location in patent: Paragraph 0153; 0154 ; Title/Abstract Full Text Show Details

27:Examples 26-31

Examples 26-31 (0153) In an autoclave, an ester imide (25 mmol) is dissolved in 25 ml of absolute methanol or ethanol and, after adding 5percent Pt/C (975 mg, 1 mol percent), flushing with hydrogen is carried out. 40 bar of hydrogen are then injected in, and the mixture is stirred at 25° C. and constant pressure for 16 hours. After separation off from the catalyst, the filtrate is distilled.

Synthesize Find similar

100%

Hide Experimental Procedure

Rx-ID: 5403460 Find similar reactions

G. D. Searle and Company

Patent: US6372758 B1, 2002 ; Title/Abstract Full Text Show Details

34.B:Preparation of N-hydroxy-1-(2-methoxyethyl)-4-[[4-[[4-(trifluoromethyl)benzoyl]amino]-1-piperidinyl]sulfonyl]-4-piperidinecarboxamide, monohydrochloride

Part B: To a solution of the carbamate of part A (10.0 g, 34.43 mmol) in methanol (200 mL) was added ammonium formate (6.51 g, 103.29 mmol) and 4percent Pd/C. The resulting mixture was heated at reflux for 1.5 hr. After cooling to ambient temperature the reaction mixture was filtered through a pad of Celite.(R)., washing with methanol. The filtrate was concentrated in vacuo to provide the piperidine as an off-white solid (6.90 g, 100percent).

100%

Hide Experimental Procedure

Schering Corporation

Patent: US2004/6087 A1, 2004 ; Title/Abstract Full Text Show Details

P.34.D:C.

D. Preparation of Compounds (295a) and (295b). A solution of the ester (294) from step C above (3.34 g, 7.83 mmol) in 6N HCl (20 mL) was heated to reflux overnight. The reaction was cooled to room temperature and basified with NH4OH solution, followed by extraction with CH2Cl2. The combined organic layer was dried over MgSO4, filtered, and evaporated to dryness to give a crude free piperidine (2.80 g, 100percent yield, MH+=534)

93%

G. D. Searle and Company

Hide Experimental Procedure

Patent: US6372758 B1, 2002 ; Title/Abstract Full Text Show Details

51.F:Preparation of N-hydroxy-1-(4-methylphenyl)-4-[[4-[4-(trifluoro-methoxy)phenoxy]-1-piperidinyl]-sulfonyl]-4-piperidinecarboxamide, monohydrochloride

Part F: To an overhead-stirring solution of 4 N HCl in dioxane (1.4 L, 5.6 mol) was poured the crude oil of the BOC-piperidine of Part E (203 g, 561 mmol). The solvents were then stripped and the residue was slurried in diethyl ether and filtered. The solid was dissolved in H2O (500 mL) and titrated to pH 10 with saturated potassium carbonate aqueous solution. The aqueous was extracted with dichloromethane (3*-800 ml). The organics were combined, dried over Na2SO4, filtered and concentrated to afford the piperidine, 10507-054, as a foamy solid (136 g, 93percent yield). 1H NMR showed the desired compound. Hide Details

93%

Hide Experimental Procedure

New; James S.; Christopher; William L.

Patent: US5137894 A1, 1992 ; Title/Abstract Full Text Show Details

2:F--Preparation of 4-[4-(1,2,5,6-Tetrahydropyridinyl)]thieno[3,2-c]pyridine III

F--Preparation of 4-[4-(1,2,5,6-Tetrahydropyridinyl)]thieno[3,2-c]pyridine III The procedure was identical to that used in the Example 1, step F preparation of piperidine III (vide supra). The product (III) was obtained in 93percent yield from 10 following purification by flash chromatography in 10percent methanol/chloroform. 1 H NMR (DMSO-d ) δ 9.8 (br s, 1H), 8.3 (d, 1H), 8.0 (d, 1H), 6.5 (m, 1H), 3.9 (m, 2H), 3.4 (m, 2H), 3.0 (m, 2H). 6

IR (KBr) 3400, 3055, 2750, 2454, 1733, 1600, 1380, 1240, 920 cm-1.

90%

Hide Experimental Procedure

Fisons Corporation

Patent: US4889941 A1, 1989 ; Title/Abstract Full Text Show Details

18.21.20:EXAMPLES 18-21

20. 3-Phenyl-7-(3-piperidino-2-hydroxypropoxy)flavone, piperidine; mp 148°-148.5° C. (i-PrOH), 90percent yield; isopropyl alcohol was used as the solvent. 69%

Hide Experimental Procedure

The University of Toledo; Gliatech, Inc.

Patent: US5486526 A1, 1996 ; Title/Abstract Full Text Show Details

6.1.2:6.1.2.

52-58 in Table I were synthesised in similar manner, i.e., by condensation of the asymmetric ethylchloroformate acid anhydride with 4(4-piperidyl) 1H-imidazole in the presence of triethyl amine. Commercially available 3,3-diphenylpropionic acid and 4,4-diphenylbut-3-enoic acid were used as the starting materials for compounds 52 and 54, respectively. The unsaturated alkene bond of 4,4-diphenylbut-3-enoic acid was reduced under mild conditions by Pd/C (5percent)/H2 catalysis. This intermediate was then used to synthesize compound 53. Both intermediates 3,3-diclohexylpropionic acid and 4,4-dicyclohexylbutanoic acid, used in the preparation of compounds 55 and 56, respectively, were prepared by reduction of 3,3-diphenylpropionic acid and 4,4-diphenylbutanoic acid in the presence of catalyse Rh/alumina (5percent)/H2, 5 atm. Compound No. 52, yield: 69percent; MS.:M/e 359 (M+); 1 H NMR CDCl3:imidazole H: δ 7.50 and 6.70 (s, 1 H); piperidine H: complex δ 4.60 (d, 2 H), 3.10 (m, 3 H), 2.60 (d, 2 H), 1.40 (m, 2 H); propionyl H: complex δ 3.05 (m, 1 H), 2.00 (d, 2 H); biphenyl H: complex δ 7.20 (m, 10 H), MA.: calc. C=76.85, H=7.00, N=11.68; found, 76.32, 6.72, 10.89, respectively. Compound No. 53, yield: 73percent; MS.:M/e 373 (M+); 1 H NMR CDCl3:imidazole H: δ 7.65 and 6.70 (s, 1 H); piperidine H: complex δ 4.60 (d, 2 H), 3.00 (m, 2 H), 2.50 (m, 2 H), 1.80 (m, 2 H); butanoyl H: δ 3.05 (m, 2 H), 2.40 (m, 2 H), 3.40 (m, 2 H); diphenyl H: δ 7.10 (m, 10 H). Compound No. 54, yield: 64percent; MS.:M/e 371 (M+); 1 H NMR CDCl3:imidazole H: δ 7.40 and 6.50 (s, 1 H); piperidyl H: complex δ 4.50 (d, 2 H), 3.60 (m, 3 H), 3.20 (d, 2 H), 1.50 (d, 2 H); butenyl H: complex δ 6.70 (d, 1 H), 3.50 (d, 2 H); diphenyl H:δ 7.10 (m, 10 H).

1.50 (m, 22 H). Compound No. 56, yield: 68percent; MS.: M/e 385 (M+); 1 H NMR CDCl3: imidazole H:δ 8.00 and 7.05 (s, 1 H); piperidyl H: complex δ 4.50 (d, 2 H), 3.80 (d, 2 H), 3.00 (m, 3 H), 2.10 (m, 2 H); butanoyl H: δ complex 2.80 (m, 2 H), 1.80 (m, 2 H), 1.40 (m, 1 H); dicyclohexyl

H: complex δ 1.20 (m, 22 H).

69%

Hide Experimental Procedure

The University of Toledo

Patent: US5639775 A1, 1997 ; Title/Abstract Full Text Show Details

2:6.1.2.

52-58 in Table I were synthesised in similar manner, i.e., by condensation of the asymetric ethylchloroformate acid anhydride with 4(4-piperidyl) 1H-imidazole in the presence of triethyl amine. Commercially available 3,3-diphenylpropionic acid and 4,4-diphenylbut-3-enoic acid were used as the starting materials for compounds 52 and 54, respectively. The unsaturated alkene bond of 4,4-diphenylbut-3-enoic acid was reduced under mild conditions by Pd/C (5percent)/H2 catalysis. This intermediate was then used to synthesize compound 53. Both intermediates 3,3-diclohexylpropionic acid and 4,4-dicyclohexylbutanoic acid, used in the preparation of compounds 55 and 56, respectively, were prepared by reduction of 3,3-diphenylpropionic acid and 4,4-diphenylbutanoic acid in the presence of catalyse Rh/alumina (5percent)/H , 5 atm.

Compound No. 52, yield: 69percent; MS.:M/e 359 (M+); 1 H NMR CDCl3:imidazole H: δ 7.50 and 6.70 (s, 1H); piperidine H: complex δ 4.60 (d, 2H), 3.10 (m, 3H), 2.60 (d, 2H), 1.40 (m, 2H); propionyl H: complex δ 3.05 (m, 1H), 2.00 (d, 2H); biphenyl H: complex δ 7.20 (m,

10H), MA.: calc. C=76.85, H=7.00, N=11.68; found, 76.32, 6.72, 10.89, respectively. Compound No. 53, yield: 73percent; MS.:M/e 373 (M+); 1 H NMR CDCl3: imidazole H: δ 7.65 and 6.70 (s, 1H); piperidine H: complex δ 4.60 (d, 2H), 3.00 (m, 2H), 2.50 (m, 2H), 1.80 (m, 2H); butanoyl H: δ 3.05 (m, 2H), 2.40 (m, 2H), 3.40 (m, 2H); diphenyl H: δ 7.10 (m, 10H). Compound No. 54, yield: 64percent; MS.:M/e 371 (M+); 1 H NMR CDCl3: imidazole H: δ 7.40.and 6.50 (s, 1H); piperidyl H: complex δ 4.50 (d, 2H), 3.60 (m, 3H), 3.20 (d, 2H), 1.50 (d, 2H); butenyl H: complex δ 6.70 (d, 1H), 3.50 (d, 2H); diphenyl H: δ 7.10 (m, 10H).

Compound No. 55, yield: 75percent; MS.: M/e 371 (M+); 1 H NMR CDCl3: imidazole H: δ 8.00 and 7.10 (s, 1H); piperidyl H: complex δ 4.50 (d, 2H), 3.10 (d, 2H), 2.80 (m, 3H), 1.90 (d, 2H); propionyl H: complex δ 2.60 (d, 2H), 2.00 (m, 1H); dicyclohexyl H: complex δ 1.50 (m, 22H). Compound No. 56, yield: 68percent; MS.: M/e 385 (M+); 1 H NMR CDCl3: imidazole H:δ 8.00 and 7.05 (s, 1H); piperidyl H: complex δ 4.50 (d, 2H), 3.80 (d, 2H), 3.00 (m, 3H), 2.10 (m, 2H); butanoyl H: δ complex 2.80 (m, 2H), 1.80 (m, 2H), 1.40 (m, 1H); dicyclohexyl H: complex δ 1.20 (m, 22H).

60%

Hide Experimental Procedure

Murata, Hiroko; Egawa, Masakazu; Nakashima, Harue; Kawakami, Sachiko; Ohsawa, Nobuharu; Seo, Satoshi

Patent: US2007/161793 A1, 2007 ; Title/Abstract Full Text Show Details

S.1.2:(2)

(2) Synthesis of PPr 10 g (27 mmol) of 2,3-bis(4-bromophenyl)-5,6-dihydropyrazine was put into a 500 mL three neck flask, and 100 mL of ethanol was added to be dissolved. Then, 8.8 g (54 mmol) of iron(III) chloride was added thereto, and this mixture was heated and stirred for 30 minutes at 60° C. to be reacted. After the reaction, 300 mL of water was added to the reaction mixture, a precipitated solid was dissolved in toluene. After this mixture was washed with saturated saline, the solid that was obtained by concentrating the solvent was purified by silica column chromatography. The purification by the silica column chromatography (hereinafter, also referred to as column purification) was performed as follows: first, toluene was used as a developing solvent; and a mixed solvent of toluene:ethyl acetate=1:1 was used as a developing solvent. After the column purification, the solvent of the obtained solution was concentrated to obtain 6.3 g of an orange solid of PPr in the yield of 60percent (Synthesis Scheme (e-2)). 42.3%

Hide Experimental Procedure

BTG International Limited

Patent: US2002/168369 A1, 2002 ; Title/Abstract Full Text Show Details

1-(3,4-dimethoxycinnamoyl)piperidine (RV-G04)

1-(3,4-dimethoxycinnamoyl)piperidine (RV-G04) 1H-NMR (CDCl ) 60 MHz δ: 7.61 (1H, CH=CH), 7.23 (1H, ArH), 6.98(1H, ArH) 6.82 (1H, J=1.8 ArH) 6.68 (1H, CH=CH), 3.58-3.65 (br, 4H, CH -N-CH (piperidine)) 1.5-1.8 (6H, CH CH CH (piperidine)) 3.91 (s, 6H, OCH ) ) 3 2 2 22 2 3 2 MS m/z (percent): 275(M+62), 192 (48), 191 (100), 161 (18), 118 (11), 84 (26), 77 (12), yield 42.3percent 42.3%

Hide Experimental Procedure

BTG International Limited

Patent: US6680391 B2, 2004 ; Title/Abstract Full Text Show Details

1-(3,4-dimethoxycinnamoyl)piperidine (RV-G04)

1-(3,4-dimethoxycinnamoyl)piperidine (RV-G04) 1H-NMR (CDCl ) 60 MHz δ: 7.61 (1H, CH=CH), 7.23 (1H, ArH), 6.98(1H, ArH) 6.82 (1H, J=1.8 ArH) 6.68 (1H, CH=CH), 3.58-3.65 (br, 4H, CH -N-CH (piperidine)) 1.5-1.8 (6H, CH CH CH (piperidine)) 3.91 (s, 6H, OCH ) ) 3 2 2 22 2 3 2 MS m/z (percent): 275(M+ 62), 192 (48), 191 (100), 161 (18), 118 (11), 84 (26), 77 (12), yield 42.3percent 33%

Hide Experimental Procedure

Duan, Jingwu; King, Bryan W.; Decicco, Carl; Maduskuie JR., Thomas P.; Voss, Matthew E.

Patent: US2002/13341 A1, 2002 ; Title/Abstract Full Text Show Details

24.a:1-[(1,1-dimethylethoxy)carbonyl]-N-hydroxy-4-[[[4-[(2-methyl-4-quinolinyl)methoxy]benzoyl]amino]methyl]-4-piperidinecarboxamide

(24a) To a solution of methyl cyanoacetae (0.478 g, 4.82 mmol) and bis-(2-bromo-ethyl)carbamic acid benzyl ester (1.76 g, 4.82 mmol) in dimethylformamide (4 mL) was added sodium hydride (0.425 g, 10.63 mmol, 60percent dispersion in mineral oil). The mixture was heated at 60° C. for 12 h. After cooling to rt, the mixture was partitioned between ethyl acetate (20 mL) and water (15 mL). The layers were separated, the organic layer washed with water (2*15 mL) and brine (2*15 mL), dried, and concentrated under reduced pressure. Purification of the crude material by silica gel chromatography (1:1 methylene chloride:hexanes) gave the desired piperidine (475 mg, 33percent). 20%

Hide Experimental Procedure

Eli Lilly and Company

Patent: US5576321 A1, 1996 ; Title/Abstract Full Text Show Details

Eli Lilly and Company

Patent: US5627196 A1, 1997 ; Title/Abstract Full Text Show Details

Eli Lilly and Company

Patent: US5614523 A1, 1997 ; Title/Abstract Full Text Show Details

163:Preparation of 1-(4-indolyloxy)-3-[4-hydroxy-4-(1H-indol-5-yl)piperidin-1-yl]propane ethanedioate

EXAMPLE 163 Preparation of 1-(4-indolyloxy)-3-[4-hydroxy-4-(1H-indol-5-yl)piperidin-1-yl]propane ethanedioate The title compound was prepared in similar fashion from 1-chloro-3-(1H-indole-4-oxy)propane and 4-hydroxy-4-(1H-indol-5-yl)piperidine (which was prepared by treatment of the potassium salt of 5-bromoindole with tert-butyllithium in tetrahydrofuran at -78° C., followed by quenching with N-benzyl-4-piperidone in tetrahydrofuran, and hydrogenolysis of the resulting adduct with palladium on carbon in ethanol, to give the desired piperidine in 20percent yield). 20%

Hide Experimental Procedure

Eli Lilly and Company

Patent: US5741789 A1, 1998 ; Title/Abstract Full Text Show Details

163:Preparation of 1-(4-indolyloxy)-3-[4-hydroxy-4-(1H-indol-5-yl)piperidin-1-yl]propane Ethanedioate

EXAMPLE 163 Preparation of 1-(4-indolyloxy)-3-[4-hydroxy-4-(1H-indol-5-yl)piperidin-1-yl]propane Ethanedioate The title compound was prepared in similar fashion from 1-chloro-3-(1H-indole-4-oxy)propane and 4-hydroxy-4-(1H-indol-5-yl)piperidine (which was prepared by treatment of the potassium salt of 5-bromoindole with tert-butyllithium in tetrahydrofuran at -78° C., followed by quenching with N-benzyl-4-piperidone in tetrahydrofuran, and hydrogenolysis of the resulting adduct with palladium on carbon in ethanol, to give the desired piperidine in 20percent yield). 20%

Hide Experimental Procedure

Eli Lilly Company

Patent: US5789402 A1, 1998 ; Title/Abstract Full Text Show Details

163:Preparation of 1-(4-indolyloxy)-3-[4-hydroxy-4-(1H-indol-5-yl)piperidin-1-yl]propane ethanedioate

Example 163 Preparation of 1-(4-indolyloxy)-3-[4-hydroxy-4-(1H-indol-5-yl)piperidin-1-yl]propane ethanedioate The title compound was prepared in similar fashion from 1-chloro-3-(1H-indole-4-oxy)propane and 4-hydroxy-4-(1H-indol-5-yl)piperidine (which was prepared by treatment of the potassium salt of 5-bromoindole with tert-butyllithium in tetrahydrofuran at -78° C., followed by quenching with N-benzyl-4-piperidone in tetrahydrofuran, and hydrogenolysis of the resulting adduct with palladium on carbon in ethanol, to give the desired piperidine in 20percent yield). 12%

Hide Experimental Procedure

Agouron Pharmaceuticals, Inc.

Patent: US6534530 B1, 2003 ; Title/Abstract Full Text Show Details

11:Preparation of Product Cbz-L-Leu-L-Phe-L-(N-Ac-amino-Ala)-C(O)-Piperidine

Preparation of Product Cbz-L-Leu-L-Phe-L-(N-Ac-amino-Ala)-C(O)-Piperidine By a method analogous to that used to prepare compound 10, [1-(acetylaminomethyl)-2,3-dioxo-3-piperidin-1-ylpropyl]carbamic acid benzyl ester (54.4 mg, 0.14 mmol, 1 equiv) was deprotected and coupled with Cbz-L-Leu-L-Phe-OH (59.4 mg, 0.14 mmol, 1.0 equiv). After chromatography (5percent CH3OH in CH2Cl2), Cbz-L-Leu-L-Phe-L-(N-Ac-amino-Ala)-C(O)-piperidine (10.5 mg, 12percent yield) was obtained as a colorless film. Rf=0.40 (5percent CH3OH in CH2Cl2). IR (cm-1) 3302, 1657, 1537. 1H NMR (CDCl3) δ0.80-0.97 (m, 6H), 1.341.98 (m, 9H), 3.09-3.19 (m, 2H), 3.37-4.20 (m, 5H) (m, 3H), 5.05-5.22 (m, 2H), 5.95-6.58 (m, 3H), 7.12-7.46 (m, 10H). MS (FAB) 636 (MH+), 658 (MNa+).

Reinigung der Nitrosoverbindung mit HCl in Toluol (dabei erhaelt man das salzsaure Piperidin);

Vorlaender; Wallis

Justus Liebigs Annalen der Chemie, 1906 , vol. 345, p. 270,281 Full Text Show Details

Venot,A.

Bulletin de la Societe Chimique de France, 1972 , p. 4736 - 4743 Full Text View citing articles Show Details

Julia,M.; Binet du Jassonneix,C.

Bulletin de la Societe Chimique de France, 1975 , p. 743 - 750 Full Text View citing articles Show Details

Zav'yalov,S.I.; Ezhova,G.I.

Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1977 , vol. 26, p. 2226 Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1977 , vol. 26, p. 2392 - 2393 Full Text View citing articles Show Details

Babayan,A.T. et al.

Zhurnal Organicheskoi Khimii, 1973 , vol. 9, p. 1149 - 1156,1178 - 1184 Full Text View citing articles Show Details

Babayan,A.T. et al.

Zhurnal Organicheskoi Khimii, 1973 , vol. 9, p. 1156 - 1163,1185 - 1191 Full Text View citing articles Show Details

Reinecke; Daubert

Journal of Organic Chemistry, 1973 , vol. 38, p. 3281,3285 Full Text Show Details

Seebach; Wykypiel

Synthesis, 1979 , p. 423 Full Text Show Details

Petersen; Norris

Acta Chemica Scandinavica (1947-1973), 1966 , vol. 20, p. 591 Full Text Show Details

ICI

Patent: DE1138398 , 1962 ; Chem.Abstr., 1963 , vol. 58, # 9096c Full Text Show Details

Feroci; Lund

Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1976 , vol. 30, p. 651 Full Text Show Details

Hendrickson; Bergeron

Tetrahedron Letters, 1973 , p. 3839 Full Text View citing articles Show Details

Abley et al.

Journal of the Chemical Society [Section] C: Organic, 1971 , p. 840,844 Full Text Show Details

Solov'ev et al.

Meditsinskaya Promyshlennost SSSR, 1965 , vol. 19, # 4 p. 9,10-12 Chem.Abstr., 1965 , vol. 63, # 5604 Full Text Show Details

Grewe et al.

Chemische Berichte, 1970 , vol. 103, p. 3752,3766 Full Text Show Details

Denney et al.

Phosphorus and the Related Group V Elements, 1971 , vol. 1, p. 151 Full Text Show Details

Broadbent; Selin

Journal of Organic Chemistry, 1963 , vol. 28, p. 2343 Full Text View citing articles Show Details

Rylander; Cohn

Pr. 2. int. Congr. Catalysis Paris, Vol.1Chem.Abstr., 1960 , p. 977 - 984 Pr. 2. int. Congr. Catalysis Paris, Vol.1Chem.Abstr., 1961 , # 24516 Full Text Show Details

Kindler; Matthies

Chemische Berichte, 1963 , vol. 96, p. 924,927 Full Text Show Details

Kindler; Matthies

Chemische Berichte, 1962 , vol. 95, p. 1992,1997 Full Text Show Details

Celanese Corp. of America

Patent: GB772446 ; Chem.Abstr., 1960 , # 1558 Full Text Show Details

Scherico Ltd.

Patent: CH566287US3956390 , 19751976 ; Chem.Abstr., vol. 85, # 62788 Full Text Show Details

Scherico Ltd.

Patent: DE2118286 , 1971 ; Chem.Abstr., 1972 , vol. 76, # 13255f Full Text Show Details

Hitachi Chemical Co

Patent: DE2008443 , 1970 ; Chem.Abstr., vol. 74, # 3400 Full Text Show Details

Jardine; McQuillin

Journal of the Chemical Society [Section] D: Chemical Communications, 1970 , p. 626 Full Text View citing articles Show Details

Brown et al.

Journal of Organometallic Chemistry, 1977 , vol. 139, p. C1 Full Text View citing articles Show Details

Lijinsky; Epstein

Nature (London, United Kingdom), 1970 , vol. 225, p. 21,22 Full Text Show Details

Balandin; Roshdestwenskaja

Zhurnal Fizicheskoi Khimii, 1960 , vol. 34, p. 872,873 p. 414 Full Text Show Details

Cuvigny; Larcheveque

Journal of Organometallic Chemistry, 1974 , vol. 64, p. 315,321 Full Text Show Details

Fremesy; Fields

Journal of Organic Chemistry, 1964 , vol. 29, p. 2240,2243 Full Text Show Details

Broadbent; Seegmiller

Journal of Organic Chemistry, 1963 , vol. 28, p. 2347,2350 Full Text Show Details

Hide Experimental Procedure

AJINOMOTO CO. INC

Patent: US2003/220268 A1, 2003 ; Title/Abstract Full Text Show Details

Process 2 Removal of Fmoc Group

Process 2 Removal of Fmoc Group A DMF solution of 20percent piperidine (25 mL) was added to the resin obtained in Process 1 and reacted for 15 minutes. After removing the solvent, the resin was washed with DMF and dichloromethane three times each, and dried under reduced pressure.

Hide Experimental Procedure

AstraZeneca AB

Patent: US2003/187002 A1, 2003 ;

Title/Abstract Full Text Show Details

260:Preparation of Compound 437 in Table 17

EXAMPLE 260 Preparation of Compound 437 in Table 17 An analogous reaction to that described in example 254 but starting with piperidine (0.4 ml, 3.0 mmol) yielded compound 437 in Table 17 (67 mg, 59percent). MS ES+: 569.5 (M+H)+ 1H-NMR (DMSOd ): 1.40 (m, 2H); 1.52 (m, 4H); 1.95 (m, 2H); 2.42 (m, 4H); 2.48 (t, 2H); 3.89 (s, 2H); 3.97 (s, 3H); 4.20 (t, 2H); 7.25 (s, 1H); 7.33 (m, 1H); 7.39 (s, 1H); 7.41 (ddd, 1H); 7.82 (m, 1H); 8.11 (s, 1H); 8.68 (s, 1H); 10.51 (s, 1H). 6

Hide Experimental Procedure

Cao, Sheldon Xiaodong; Bounaud, Pierre-Yves; Chen, Xiaohua; Chung, Hyun-Ho; KC, Sunil Kumar; Min, Changhee; Yang, Jae Young; Long, Melissa C.

Patent: US2003/187007 A1, 2003 ; Title/Abstract Full Text Show Details

...e twentieth embodiment, wherein said heteroaryl ring is selected from the group consisting of furan, thiophene, pyrrole, pyrroline, pyrrolidine, oxazole, thiazole, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, isoxazole, isothiazole, triazole, thiadiazole, oxadiazole pyran, piperidine, morpholine, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, and triazine.

Hide Experimental Procedure

Cao, Sheldon Xiaodong; Bounaud, Pierre-Yves; Chen, Xiaohua; Chung, Hyun-Ho; KC, Sunil Kumar; Min, Changhee; Yang, Jae Young; Long, Melissa C.

Patent: US2003/187007 A1, 2003 ; Title/Abstract Full Text Show Details

pyridine, piperidine, morpholine, thiomorpholine, pyridazine, pyrimidine, pyrazine, piperazine, and triazine.

Hide Experimental Procedure

Kitagawa, Yoshinori; Ishikawa, Koichi; Sawada, Haruko; Araki, Yasuo; Assmann, Lutz

Patent: US2003/176477 A1, 2003 ; Title/Abstract Full Text Show Details

The following compounds may be mentioned as examples of substances of the formula (V): 4-chlorophenol, thiophenol, piperidine, sodium benzenesulfinate.

Hide Experimental Procedure

AstraZeneca AB

Patent: US2003/187002 A1, 2003 ; Title/Abstract Full Text Show Details

Preparation of Compound 480 in Table 17

EXAMPLE 303 Preparation of Compound 480 in Table 17 An analogous reaction to that described in example 253 but starting with piperidine (344 mg, 4.0 mmol) yielded compound 480 in Table 17 (52 mg, 40percent). MS ES+: 565 (M+H)+ 1H-NMR (DMSOd , TFA): 1.43 (m, 1H); 1.69 (m, 3H); 1.87 (d, 2H); 2.30 (m, 2H); 2.96 (t, 2H); 3.27 (t, 2H); 3.55 (d, 2H); 3.99 (s, 3H); 4.00 (s, 2H); 4.31 (t, 2H); 7.15 (d, 1H); 7.31 (s, 1H); 7.37 (t, 1H); 7.47 (d, 1H); 7.65 (s, 1H); 7.86 (s, 1H); 7.91 (s, 1H); 9.09 (s, 1H); 6

10.56 (s, 1H).

Hide Experimental Procedure

AstraZeneca AB

Patent: US2003/187002 A1, 2003 ;

Title/Abstract Full Text Show Details

Preparation of Compound 492 in Table 17

EXAMPLE 315 Preparation of Compound 492 in Table 17 An analogous reaction to that described in example 255 but starting with piperidine (281 mg, 3.3 mmol) yielded compound 492 in Table 17 (81 mg, 64percent). MS ES+: 569 (M+H)+ 1H-NMR (DMSOd ): 1.38 (m, 2H); 1.50 (m, 4H); 2.34 (brs, 4H); 2.41 (t, 2H); 3.90 (s, 2H); 3.96 (s, 3H); 4.19 (t, 2H); 6.93 (t, 1H); 7.24 (s, 1H); 7.34 (d, 2H); 7.38 (s, 1H); 8.11 (brs, 1H); 8.67 (s, 1H); 10.63 (s, 1H); 11.98 (brs, 1H). 6

Hide Experimental Procedure

Marzabadi, Mohammad R.; Wetzel, John; DeLeon, John E.; Lagu, Bharat; Gluchowski, Charles; Noble, Stewart; Nagarathnam, Dhanapalan

Patent: US2003/69261 A1, 2003 ; Title/Abstract Full Text Show Details

Piperidine Side Chain Intermediates

Piperidine Side Chain Intermediates TERT-BUTYL 4-{[(TRIFLUOROMETHYL)SULFONYL]OXY}-1,2,3,6-TETRAHYDRO-1-PYRIDINECARBOXYLATE: n-Butyl lithium (17.6 mL, 44.2 mmol, 2.5 M in hexanes) was added to a solution of diisopropyl amine (96.2 mL, 44.2 mmol) in 40 mL of dry THF at 0° C. and stirred for 20 minutes. The reaction mixture was cooled to -78° C. and tert-butyl 4-oxo-1-piperidinecarboxylate (Aldrich Chemical Company, 40.0 mmol) in THF (40 mL) was added dropwise to the reaction mixture and stirred for 30 minutes. Tf2NPh (42.0 mmol, 15.0 g) in THF (40 mL) was added dropwise to the reaction mixture and stirred at ° C. overnight. The reaction mixture was concentrated in vacuo, re-dissolved in hexanes:EtOAc (9:1), passed through a plug of alumina and the alumina plug was washed with hexanes:EtOAc (9:1). The combined extracts were concentrated to yield 16.5 g of the desired product that was contaminated with some starting Tf2NPh.

Hide Experimental Procedure

Thompson, Lorin A.; Kasireddy, Padmaja

Patent: US2003/73701 A1, 2003 ; Title/Abstract Full Text Show Details

132.b:Example 132(b)

Example 132(b) The oil from above was dissolved in 25 mL of methanol and 380 mg of 20percent paddadium on carbon was added. The reaction solution was placed under 50 p.s.i. of dihydrogen and shaken at rt for 16 h. The catalyst was then removed by filtration and the resulting piperidine was used without further purification.

Hide Experimental Procedure

KOWA CO., LTD.

Patent: US2003/119838 A1, 2003 ; Title/Abstract Full Text Show Details

92:Example 92

Example 92 Preparation of 6-(4-fluoro-3-methylphenyl)-2-isobutyl-4-(piperidino) methyl-2H-pyridazin-3-one 6-(4-Fluoro-3-methylphenyl)-2-isobutyl-4-methane-sulfonyloxymethyl-2H-pyridazin-3-one (80 mg, 0.22 mmol) and piperidine (55 mg, 0.65 mmol) were dissolved in ethanol (0.5 mL), and the mixture was heated at 80° C. for 1 hour under stirring.

Hide Experimental Procedure

GeneSoft, Inc.

Patent: US2003/83268 A1, 2003 ; Title/Abstract Full Text Show Details

V:EXAMPLE V

In situ mesylation of alcohol 272 and nucleophilic aromatic substitution of the mesyloxy group by an amine gave the final compounds (piperidine for Ib-90; pyrrolidine for Ib-91).

Hide Experimental Procedure

Botstein, David; Brown, Patrick O.; Perou, Charles M.; Ring, Brian; Ross, Douglas; Seitz, Rob; van de Rijn, Jan Matthijs

Patent: US2003/86934 A1, 2003 ; Title/Abstract Full Text Show Details

Peptide (Synthesised by Research Genetics, Inc. Details given below) Piperidine (Cat. No. 80640, Fluka, available through Sigma) Sodium Bicarbonate (Cat. No. BP328-1, Fisher) Sodium Borate (Cat. No. B9876, Sigma) Sodium Carbonate (Cat. No. BP357-1, Fisher) Sodium Chloride (Cat. No. BP 358-10, Fisher) Sodium Hydroxide (Cat. No. SS 255-1, Fisher)

Hide Experimental Procedure

Aquila, Brian M.; Cuny, Gregory D.; Hauske, James R.; Shao, Liming; Wu, Xinhe

Patent: US2001/56090 A1, 2001 ; Title/Abstract Full Text Show Details

8:Synthesis of N-1-Phenethyl[3-(1'-(N-(2'-ketobenzyimidazolinyl)))methylene]piperidine

EXAMPLE 8 Synthesis of N-1-Phenethyl[3-(1'-(N-(2'-ketobenzyimidazolinyl)))methylene]piperidine A solution of 9 (0.096 mmol, 35 mg), phenylacetaldehyde (10.0 equiv, 0.96 mmol, 110 μL), and 10percent Pd-C (10 mg) in CH3OH (2 mL) at 25° C. was treated with H2 at 48 psi. The reaction mixture was stirred for 5 h. The reaction mixture was filtered through Celite and the solvents were removed in vacuo. Chromatography (PTLC, SiO2, 20 cm*20 cm, 1 mm, 9:1 EtOAc-CH3OH) provided 10 (13 mg, 32 mg theoretical, 41percent) as a white solid: Rf 0.25 (SiO2, 9:1 EtOAc-CH3OH); 1H NMR (CDCl3, 300 MHz) 8 9.75 (s, 1H), 7.36-7.00 (m, 9H), 3.83-3.80 (d, 2H), 2.98-2.76 (m, 4H), 2.66-2.54 (m, 2H), 2.38-2.22 (m, 1H), 2.20-1.97 (m, 2H), 1.84-1.54 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ 156.0, 140.7, 130.9, 129.0, 128.6, 128.1, 126.2, 121.7, 121.5, 109.8, 108.5, 61.2, 58.1, 54.1, 44.8, 36.1, 30.0, 28.7, 24.9; LRMS m/z 335 (M+, C21H25N3O, requires 335).

Hide Experimental Procedure

Heerding, Dirk; Samanen, James Martin

Patent: US2002/55499 A1, 2002 ; Title/Abstract Full Text Show Details

1.a:a

a N-t-Butoxycarbonyl-4-(2-hydroxyethyl)piperidine To a solution of 4-(2-hydroxyethyl)pyridine (1.00 g, 8.12 mmol) in 1N HCl (10 mL) in a Parr hydrogenation apparatus was added Pt2O (10 mg). The mixture was hydrogcnated at 50 psi for 7 h. After venting the hydrogen, the catalyst was removed by filtration through celite and the celite rinsed with H2O (10 mL). Concentration of the combined filtrate afforded the crude 4-(2-hydroyethyl)piperidine MS (ES+) m/z 129.9 (M+H+).

Hide Experimental Procedure

Aquila, Brian M.; Cuny, Gregory D.; Hauske, James R.; Shao, Liming; Wu, Xinhe

Patent: US2001/56090 A1, 2001 ; Title/Abstract Full Text Show Details

10:Synthesis of N-1-tert-Butoxycarbonyl[3-R-(1'-(N-(2'-ketobenzyimidazolinyl)))methylene]piperidine (12)

EXAMPLE 10 Synthesis of N-1-tert-Butoxycarbonyl[3-R-(1'-(N-(2'-ketobenzyimidazolinyl)))methylene]piperidine (12) A solution of 11 (11.2 mmol, 3.58 g) in THF (15 mL) at 0° C. was treated with 1.0M BH3-THF (2.0 equiv, 22 mmol) under Ar. The reaction mixture was then heated to 80° C. and allowed to stir for 12 h. The reaction mixture was then cooled to 0° C. and quenched with 10percent aqueous HCl. The pH was adjusted to 10 with 10percent aqueous NaOH and the reaction mixture was extracted with EtOAc (3*25 mL). The organics were washed with saturated aqueous NaCl, and dried over MgSO4. Based on poor stability the material was carried directly to the next step. The above compound in THF (50 mL) at 0° C. was treated with phosgene (20percent in toluene) (2.0 equiv, 21.5 mmol) and triethylamine (2.0 equiv, 21.5 mmol, 3.00 mL) under Ar. The reaction mixture warmed to 25° C. and stirred for 3 h. The reaction mixture was cooled to 0° C. and quenched with 10percent aqueous NaHCO3. The reaction mixture was then made acidic with 10percent aqueous HCl and extracted with EtOAc (3*25 mL). The organics were washed with saturated aqueous NaCl, dried over MgSO4, and the solvents were removed in vacuo. Chromatography (SiO2, 2.5 cm*30.5 cm, 3:2EtOAc-hexane) provided 12 (2.16 g, 3.56 mg theoretical, 61percent) as a white solid; LRMS m/z 331 (M+, C18H25N3O3, requires 331).

Hide Experimental Procedure

Millennium Pharmaceuticals, Inc.

Patent: US2002/169155 A1, 2002 ; Title/Abstract Full Text Show Details

234:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine

EXAMPLE 234 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and follow hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) d: 1.65-1.93 (2H, m), 1.94-2.28 (4H, m), 2.34-2.70 (4H, m), 2.81 (1H, m), 2.96 (2H, m), 3.78 (3H, s), 5.28 (2H, brs), 6.09 (1H, t), 6.70-7.42 (8H, m), 7.53-7.72 (2H, m), 8.28 (1H, brs), 8.49 (1H, m). 3

Hide Experimental Procedure

Chee, Jennifer; Johanson, Jill N.; Kayser, Frank; Parsons, William H.; Rupprecht, Kathleen M.

Patent: US2002/13348 A1, 2002 ; Title/Abstract Full Text Show Details

53:1-(2,4-Dichlorobenzyl)-3-(S)-(4-(2-ethoxy-2-methyl-1-propyl)piperidinylmethyl)-4-(S)-(3-thienyl)pyrrolidine

The following Examples 54 to 55 were prepared from 1-(2,4-dichlorobenzyl)-3-(R)-formyl-4-(S)-(3-thienyl)pyrrolidine according to procedures described in Example 4. The piperidine sidechains were prepared from 1-t-butoxycarbonyl-4-(2-hydroxy-1-propyl)piperidine (Example 26) according to procedures described in Example 34.

Hide Experimental Procedure

Chee, Jennifer; Johanson, Jill N.; Kayser, Frank; Parsons, William H.; Rupprecht, Kathleen M.

Patent: US2002/13348 A1, 2002 ; Title/Abstract Full Text Show Details

55:1-(2,4-Dichlorobenzyl)-3-(S)-(4-(2-ethoxy 1-propyl)piperidinylmethyl)-4-(S)-(3-thienyl)pyrrolidine

The following Examples 56 to 58 were prepared from 1-(2,4-dichlorobenzyl)-3-(R)-formyl-4-(S)-(3-thienyl)pyrrolidine according to procedures described in Example 4. The piperidine sidechains were prepared as described.

Hide Experimental Procedure

LULY, JAY R.; NAKASATO, YOSHISUKE; OHSHIMA, ETSUO; SONE, HIROKI; KOTERA, OSAMU; HARRIMAN, GERALDINE C.B.

Patent: US2002/119973 A1, 2002 ; Title/Abstract Full Text Show Details

234:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine

EXAMPLE 234 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and follow hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) d: 1.65-1.93 (2H,m), 1.94-2.28 (4H,m), 2.34-2.70 (4H,m), 2.81 (1H,m), 2.96 (2H,m), 3.78 (3H,s), 5.28 (2H,brs), 6.09 (1H,t), 6.70-7.42 (8H,m), 7.53-7.72 (2H,m), 8.28 (1H,brs), 8.49 (1H,m). 3

Hide Experimental Procedure

G. D. Searle and Company

Patent: US6372758 B1, 2002 ; Title/Abstract Full Text Show Details

3.3:Preparation of tetrahydro-N-hydroxy-4-[[4-[[4-[(trifluoromethyl)thio]phenyl]-thio]-1-piperidinyl]sulfonyl]-2H-pyran-4-carboxamide

Part 3: Preparation of: The HCl salt of Part 2 (6 g, 30 mmol) and triethylamine (Aldrich, 10 mL, 110 mmol) were slurried in CH2Cl2 (100 mL) and cooled to 0° C. A solution of methane sulfonyl chloride (Aldrich, 4 g, 45 mmol) in CH2Cl2 (20 mL) was slowly added, maintaining the temperature below 10° C. After the addition, the ice bath was removed and the reaction stirred 1 hr as it warmed to ambient temperature. After the disappearance of the starting material, the solvent was removed and the residue was taken up in ethyl acetate (100 mL) and H2O (30 mL). Once separated, the organic layer was washed with 5percent KHSO4 (3*-50 mL) and brine (1*-50 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated to afford the piperidine as an oily solid that was recrystallized from diethyl ether, affording an off-white solid (3.5 g). 1H NMR and mass spectrum showed the desired compound.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US6432981 B1, 2002 ; Title/Abstract Full Text Show Details

52:EXAMPLE 52

EXAMPLE 52 Using essentially the same procedure as in Example 21, Steps L-Q, but substituting bromomethylcyclobutane in Step L, using the required lower isomer from Step M, and the appropriate piperidine in Step O, the following title compounds were obtained.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US6432981 B1, 2002 ; Title/Abstract Full Text Show Details

53:EXAMPLE 53

EXAMPLE 53 Using essentially the same procedure as in Example 21, Steps L-Q, but substituting bromomethylcyclobutane in Step L, using the higher isomer from Step M, and the appropriate piperidine in Step O, the following title compounds were obtained.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US6358979 B1, 2002 ; Title/Abstract Full Text Show Details

71:EXAMPLE 71

EXAMPLE 71 Using essentially the same procedures as in Example 65, Steps E-I, but substituting D-leucine-t-butyl ester in Step E, using the higher Rf isomer from Step F, and substituting the appropriate piperidine in Step H, the following title compounds were prepared.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US6358979 B1, 2002 ; Title/Abstract Full Text Show Details

73:EXAMPLE 73

EXAMPLE 73 Using essentially the same procedures as in Example 72 and Example 65, Steps E-I but substituting (R)-t-butylglycine t-butyl ester in Step E and skipping Step F, using the higher R isomer from Step E (as in Example 72), and substituting the appropriate piperidine in Step H,

the following title compounds were prepared.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US6358979 B1, 2002 ; Title/Abstract Full Text Show Details

75:EXAMPLE 75

EXAMPLE 75 Using essentially the same procedures as in Example 74 and Example 65, Steps E-I, but substituting (R)-t-butylglycine t-butyl ester in Step E, using the higher Rf isomer from Step F, and substituting the appropriate piperidine in Step H, the following title compounds were prepared.

Hide Experimental Procedure

BTG International Limited

Patent: US6346539 B1, 2002 ; Title/Abstract Full Text Show Details

1-(3,4-dimethoxycinnamoyl)piperidine (RV-G04)

1-(3,4-dimethoxycinnamoyl)piperidine (RV-G04) 1H-NMR (CDCl ) 60 MHz δ: 7.61(1H, CH=CH), 7.23(1H, ArH), 6.98(1H, ArH) 6.82(1H, J=1.8 ArH) 6.68(1H, CH=CH), 3.58-3.65(br, 4H, CH -N-CH (piperidine)) 1.5-1.8(6H, CH -CH CH (piperidine)) 3.91(s, 6H, OCH ) ), MS m/z (percent): 275(M+62), 192(48), 191(100), 3 2 2 2 2 2 3 2

161(18), 118(11), 84(26), 77(12), yeild 42.3percent.

Hide Experimental Procedure

AJINOMOTO CO., INC.

Patent: US2002/133005 A1, 2002 ; Title/Abstract Full Text Show Details

Process 2:

Process 2: 4-nitrobenzyl bromide (24:X=Br) (110 mg, 0.5 mmol), potassium carbonate (352 mg, 2.55 mmol) and sodium iodide (76.5 mg, 0.5 mmol) were added to a dimethylformamide (5mil) solution of the piperidine (23) obtained in the process 1, and then stirred under the argon atmosphere at the room temperature for 2 hours. This was further stirred at 70° C. for 1 hour and was extracted with hexan-ethyl acetate (3:1) mixed solvent, and then washed with water and saturated saline solution, dried and vacuum concentrated, thus obtained a 4-nitrobenzylpiperadine compound (25:R=2,2dimethylcyclopropane) in the form of a yellow crystal (95 mg, 57percent). 1H-NMR (300 MHz, CDCl3) δ=0.69-0.73 (1H, m), 1.07 (1H, t, J=4.8 Hz), 1.13 (3H, s), 1.15 (3H, s), 1.19-1.24 (1H, m), 1.41-1.49 (1H, m), 1.93 (2H, brs), 2.12-2.21 (2H, m), 2.78 (2H, d, J=11.7 Hz), 3.58 (2H, s), 3.75-3.88 (1H, m), 5.42-5.46 (2H, m), 7.50 (2H, d, J=8.4 Hz), 8.17 (2H, d, J=8.4 Hz). MS(ESI) m/z 332 (M+H)+.

Hide Experimental Procedure

ConjuChem, Inc.

Patent: US6440417 B1, 2002 ; Title/Abstract Full Text Show Details

1:Synthesis of (2R,4R)-1-[(S)-1-phenylethyl]-4-methylpipecolate

Synthesis of (2R,4R)-1-[(S)-1-phenylethyl]-4-methylpipecolate The piperidine obtained from previous step (297 g, 1.086 mol), catalyst:[(S)-BINAP]Cl(p-Cymene)RuCl (14.9g, 50 mg/1 g) or (Bicyclo[2.2.1]hepta-2,5-diene)-[1,4-bis(diphenylpgosphino)butane]rhodium(l) tetrafluoroborate (14.9 9, 50 mg/1 g), and ethanol (1.1 L) were added into the hydrogenator. The whole system was purged several times with nitrogen, vacuum, then hydrogen, and sealed. The reaction was allowed to stir at 50° C., 150 Psi H2 (for 12 h.

Hide Experimental Procedure

Cytovia, Inc.

Patent: US6462041 B1, 2002 ; Title/Abstract Full Text Show Details

11:10-(4-Metliylpiperazinyl)-gambogyl Piperidine

EXAMPLE 11 10-(4-Metliylpiperazinyl)-gambogyl Piperidine The title compound was prepared from gambogyl piperidine and N-methylpiperazine by a procedure similar to that of Example 10. MS. 797 (M+H), 819 (M+Na), 835 (M+K), 795 (M-H). 1H NMR (CDCl ) 12.01 (s, 1H), 6.66 (d, J=9.9 Hz, 1H), 5.94 (t, 1H), 5.44 (d, J=10.2 Hz, 1H), 5.12-5.10 (m, 2H), 3.80 (d, 1H), 3.52 (d, 1H), 3.38-3.12 (m, 5H), 2.78-2.26 (m, 6H), 2.24 (s, 3H), 2.12-2.04 (m, 2H),), 1.89 (s, 3H), 1.75 (s, 3H), 1.66 (s, 6H), 1.57 (s, 3H), 1.55 (m, 3

2H), 1.34 (s, 3H), 1.32 (s, 3H), 1.11 (s, 3H).

Hide Experimental Procedure

1:Example 1

Example 1 8 g of catalyst A were placed in a basket insert in a 300 ml pressure reactor. The reactor was subsequently charged with 100 g of pyridine.

BASF Aktiengesellschaft

Patent: US6583286 B1, 2003 ; Title/Abstract Full Text Show Details

The hydrogenation was conducted with pure hydrogen at a pressure of from 150 to 250 bar and a temperature of 180° C. Hydrogenation was continued until hydrogen was no longer taken up (0.5 h) and the reactor was then let down. The pyridine conversion was 100percent. The yield of piperidine was 99percent.

Hide Experimental Procedure

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6509346 B2, 2003 ; Title/Abstract Full Text Show Details

234:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine

EXAMPLE 234 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and follow hydrogenation described in Example 58, step 3. 1H-NMR (CDCl ) δ: 1.65-1.93 (2H, m), 1.94-2.28 (4H, m), 2.34-2.70 (4H, m), 2.81 (1H, m), 2.96 (2H, m), 3.78 (3H, s), 5.28 (2H, brs), 6.09 (1H, t), 6.70-7.42 (8H, m), 7.53-7.72 (2H, m), 8.28 (1H, brs), 8.49 (1H, m). 3

Hide Experimental Procedure

BASF Aktiengesellschaft

Patent: US6583286 B1, 2003 ; Title/Abstract Full Text Show Details

2:Example 2

Example 2 8 g of catalyst A were placed in a basket insert in a 300 ml pressure reactor. The reactor was subsequently charged with 40 g of pyridine and 80 ml of THF. The hydrogenation was conducted with pure hydrogen at a pressure of 200 bar and a temperature of 120° C. Hydrogenation was continued until hydrogen was no longer taken up (2 h) and the reactor was then let down. The pyridine conversion was 100percent. The yield of piperidine was 98.6percent.

Hide Experimental Procedure

BASF Aktiengesellschaft

Patent: US6583286 B1, 2003 ; Title/Abstract Full Text Show Details

3:Example 3

Example 3 8 g of catalyst A were placed in a basket insert in a 300 ml pressure reactor. The reactor was subsequently charged with 50 g of pyridine and 80 ml of THF. The hydrogenation was conducted with pure hydrogen at a pressure of from 50 bar and a temperature of 120° C. Hydrogenation was continued until hydrogen was no longer taken up (3 h) and the reactor was then let down. The pyridine conversion was 100percent. The yield of piperidine was 98.3percent.

Hide Experimental Procedure

BASF Aktiengesellschaft

Patent: US6583286 B1, 2003 ; Title/Abstract Full Text Show Details

4:Example 4

Example 4 8 g of catalyst A were placed in a basket insert in a 300 ml pressure reactor. The reactor was subsequently charged with 40 g of pyridine and 80 ml of THF. The hydrogenation was conducted with pure hydrogen at a pressure of from 10 bar and a temperature of 120° C. Hydrogenation was continued until hydrogen was no longer taken up (12 h) and the reactor was then let down. The pyridine conversion was 100percent. The yield of piperidine was 98.1percent.

Hide Experimental Procedure

Kowa Co., Ltd.

Patent: US6605620 B1, 2003 ; Title/Abstract Full Text Show Details

P.108:Synthesis of 1-(tert-butpxycarbonyl)-4-4-butoxyphenylamino)piperidine:

PREPARATION EXAMPLE 108 Synthesis of 1-(tert-butpxycarbonyl)-4-4-butoxyphenylamino)piperidine: 1-(tert-butoxycarbonyl)-4-piperidone (5.00 g) and 4-butoxyaniline (3.95 g) was treated in the same manner as described in Preparation Example 37 to give brown powder of the title compound. Yield: 6.91 g (83percent). 1H-NMR (400 MHz, CDCl ) δ: 0.96 (t, 3H, J=7.2 Hz), 1.23-1.35 (m, 2H), 1.42-1.53 (m, 2H), 1.46 (s, 9H), 1.68-1.76 (m, 2H), 1.97-2.05 (m, 2H), 2.84-2.95 (m, 2H), 3.28-3.37 (m, 1H), 3.88 (t, 2H, J=6.6 Hz), 3.96-4.12 (m, 2H), 6.57 (d, 2H, J=9.0 Hz), 6.77 (d, 2H, J=8.8 Hz). 3

Klinge Pharma GmbH

Hide Experimental Procedure

Patent: US6593344 B1, 2003 ; Title/Abstract Full Text Show Details

represents the ring bound over the nitrogen atom of the following ring systems; pyrrolidine, piperidine, hexahydroazepine, octahydroazocine, piperazine, hexahydrodiazepine, morpholine, hexahydrooxazepine, thiomorpholine, ...

Hide Experimental Procedure

Merz Pharma GmbH and Co., KGAA

Patent: US6602862 B1, 2003 ; Title/Abstract Full Text Show Details

683: 1-amino-(1S,5S)cis-5-ethyl-1,3,3-trimethylcyclohexane,.H2O, ... N-[(1S,5S)cis-5-ethyl-1,3,3-trimethylcyclohexyl] pyrrolidine or piperidine, N-(1,3,3-trimethyl-trans-5-ethylcyclohexyl)pyrrolidine or piperidine, N-[(1R,5S)trans-5-ethyl-1,3,3-trimethylcyclohexyl] pyrrolidine or piperidine, N-(1-ethyl-3,3,5,5-tetramethylcyclohexyl)pyrrolidine or piperidine, and N-(1-propyl-3,3,5,5-tetramethylcyclohexyl)pyrrolidine or piperidine,

Hide Experimental Procedure

Boehringer Ingelheim Pharmaceuticals, Inc.

Patent: US6492529 B1, 2002 ; Title/Abstract Full Text Show Details

Boehringer Ingelheim Pharmaceuticals, Inc.

Patent: US2003/130309 A1, 2003 ; Title/Abstract Full Text Show Details

each R4, R5, R6, R7, R9, R10, R11, and R12 is independently selected from the group consisting of: morpholine, piperidine, piperazine, imidazole and

Hide Experimental Procedure

C-Chem AG

Patent: US6583265 B1, 2003 ; Title/Abstract Full Text Show Details

..., N-methyl-N-ethylamino, N,N-diethylamino, N-propyl-N-methylamino, N-methyl-N-isopropylamino, dipropylamino, diisopropylamino, N-butyl-N-methylamino or an isomer thereof, N-butyl-N-ethylamino or an isomer thereof, N-butyl-N-propylamino or an isomer thereof, N,Ndibutylamino or an isomer thereof, azetidine, pyrrolidine, piperidine, morpholine, piperazine, azabicylo[2.1.1]hexane, azanorbornane, azabicylo[2.2.2]octane,

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

12.b:Q1 =4-Methylaminocarbonyl-4-(2-oxopiperidino)piperidino; MS: m/z=582(M+1).

b. 4-(Methylaminocarbonyl)-4-(2-oxopiperidino)piperidine. A solution of the compound from (a) and 20percent palladium hydroxide on carbon in ethanol was stirred overnight under hydrogen. The mixture was filtered through diatomaceous earth and evaporated to give the piperidine; MS: m/z=240(M+1); NMR (CD3 OD): 3.45 (m,2), 3.10 (m,2), 2.96 (m,2), 2.68 (m,3), 2.32 (m,2), 2.22 (m,2), 1.90 (m,4), 1.75 (m,2).

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

13.b:Q1 =4-(N,N-Dimethylaminocarbonyl)-4-(2-oxopiperidino)-piperidino; MS: m/z=596(M+1).

b. 4-(Dimethylaminocarbonyl)-4-(2-oxopiperidino)piperidine. A solution of the compound from (a) and 20percent palladium hydroxide on carbon in ethanol was stirred overnight under hydrogen. The mixture was filtered through diatomaceous earth and evaporated to give the piperidine; MS: m/z=254(M+1); NMR (CD3 OD): 3.45 (m,2), 3.09 (m,2), 2.92 (m,8), 2.38 (m,2), 2.26 (m,2), 1.92-1.69 (m,6).

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

15.b:Q1 =4-(3-methyl-2-oxoperhydropyrimidin-1-yl)piperidino; MS: m/z=540(M+1).

b. 4-(3-Methyl-2-oxoperhydropyrimidin-1-yl)piperidine. The compound from (a) was hydrogenated under conditions similar to those described in Example 13 sub-part (b) to give the piperidine; MS: m/z=198(M+1); NMR (CD3 OD): 4.19 (m,1), 3.14 (m,4), 2.98 (m,2), 2.80 (s,3), 2.53 (m,2), 1.82 (m,2), 1.48 (m,4).

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

16.b:Q1 =4-(3-ethyl-2-oxoperhydropyrimidin-1-yl)piperidino; MS: m/z=554(M+1).

b. 4-(3-Ethyl-2-oxoperhydropyrimidin-1-yl)piperidine. The compound from (a) was hydrogenated under conditions similar to those described in Example 13 sub-part (b) to give the piperidine; MS: m/z=212(M+1); NMR (CDCl3): 4.45 (m,1), 3.38 (q,2, J=7.1), 3.17 (m,6), 2.72 (m,2), 2.15 (m,1), 1.91 (m,2), 1.62 (m,4), 1.10 (t,2, J=7.1).

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

18.f:Q1 =4-Methyl-4-(2-oxoperhydropyrimidin-1-yl)piperidino; MS: m/z=540(M+1).

f. 4-Methyl-4-(2-oxoperhydropyrirmidin-1-yl)piperidine. The compound from (e) was 15 hydrogenated under conditions similar to those described in Example 13 sub-part (b) to give the piperidine; MS: m/z=198(M+1); NMR (CD3 OD): 3.26 (m,2), 3.17 (m,2), 2.77 (m,4), 2.44 (m,2), 1.89 (m,2), 1.67 (m,2), 1.31 (s,3).

Hide Experimental Procedure

Novo Nordisk A/S

Patent: US5863903 A1, 1999 ; Title/Abstract Full Text Show Details

1:Synthesis of (3R,4R,5R)-3,4-dihydroxy-5-Hydroxymethylpiperidine

(3R,4R,5R)-3,4-Dihydroxy-5-hydroxymethylpiperidine hydrochloride: (3R,4R,5R)-3-Benzyloxy-4-hydroxy-5-hydroxymethylpiperidine (0.527 g, 2.2. mmol) was dissolved in 0.5M HCl (5.3 ml) and ethanol (50 ml) and 5percent palladium charcoal (300 mg) was added. The mixture was hydrogenated at 101 kPa and 20° C. for 18 hours. The reaction mixture was filtrated and concentrated to give the product in 93percent (0.375 g) yield. 13C-NMR (50 MHz, D2 O): d 70.7 og 68.1 (C-3 og C-4); 58.6 (C-5'); 46.2 og 44.4 (C-2 og C-6); 40.6 (C-5). 1H-NMR (500 MHz, D2 O, Ph<1, ref. 4.63 ppm): d 3.72 (dd, 1H, H-5b',J5a',5b' =11.5, J5,5b' =3.3 Hz); 3.67 (ddd, 1H, H-3, J3,2ax =11.2, J3,4 =8.9,J3,2eq =4.9 Hz); 3.64 (dd, 1H, H-5a', J5 a',5b'=11.5,J5a',5 =6.2 Hz); 3.43 (ddd, 1H, H-2eq, J2eq,2ax =12.7, J2eq,3 =4.9, J2eq,6eq =2.0); 3.42 (dd, 1H, H-4, J4,5 =10.5, J4,3 =8.9 (Hz); 3.41 (ddd, 1H, H-6eq, J6eq,6ax =13.4, J6eq,5 =3.8, J6eq,2eq =2.0 Hz); 2.87, 12.7, J2ax,3 =11.2 Hz); 1.86 ppm (ddddd, 1H, H-5). If necessary, the piperidine could be chromatographed using ethanol/NH4OH (25percent aqueous) (10:1) to give the free piperidine. Analytical calculation for C6 H13 NO3: C: 48.97; H: 8.90; N: 9.52. Found: C: 48.46; H: 9.33; N: 9.17.

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

20.f:Q1 =4-(2-Oxoperhydropyrimidin-1-yl)-4-(pyrrolidino-carbonyl)piperidino; MS: m/z=623(M+1).

f. 4-(2-Oxoperhydropyrimidin-1-yl)-4-(pyrrolidine-1-yl-carbonyl)piperidine. The compound from (e) was hydrogenated under conditions similar to those described in Example 13 sub-part (b) to give the piperidine; MS: m/z=281(M+1); NMR (CD3 OD): 3.41 (m,6), 3.16 (m,4), 2.98 (m,2), 2.28 (m,2), 2.00-1.78 (m,8).

Hide Experimental Procedure

Zeneca Limited

Patent: US5889024 A1, 1999 ; Title/Abstract Full Text Show Details

21.c:Q1 =4-(5,5-Dimethyl-2-oxoperhydropyrimidin-1-yl)-piperidino; MS: m/z=554(M+1).

c. 4-(2-Oxo-5,5-dimethylperhydropyrimidin-1-yl)piperidine. The compound from (b) was hydrogenated under conditions similar to those described in Example 13 sub-part (b) to give the piperidine; MS: m/z=212(M+1); NMR (CD3 OD): 4.28 (m,1), 3.10 (m,2), 2.92 (m,2), 2.89 (m,2), 2.66 (m,2), 1.59 (m,4), 1.03 (s,6).

Hide Experimental Procedure

Sankyo Company, Limited

Patent: US6090802 A1, 2000 ; Title/Abstract Full Text Show Details

4:(1R,5S,6S)-6-[(1R)-1-Hydroxyethyl]-1-methyl-2-[(2S,4S)-2-[(3S)-3-(piperidin-2-ylcarbonylamino)pyrrolidin-1-ylcarbonyl]pyrrolidin-4-ylthio]-1-carbapen-2-em-3-carboxylic acid (Exemplified Compound 1-11) STR395

From the fraction eluted secondly, an isomer (R- or S-form) (78.2 mg) at the 2-position of the piperidine having a low polarity was obtained. Infrared absorption spectrum (KBr) νmax cm-1:3280,1757,1634,1596, 1453, 1386, 1285, 1182, 1147. Nuclear magnetic resonance spectrum (400 MHz, D2 O) δ ppm: 1.22 (3H, t, J=6.7 Hz), 1.30 (3H, dd, J=6.2, 2.1 Hz), 1.52-1.77 (4H, m), 1.83-2.36 (5H, m), 2.65-2.80 (1H, m), 2.95-3.14 (2H, m), 3.16-3.25 (1H, m), 3.29-3.89 (9H, m), 3.95-4.08 (1H, m), 4.19-4.32 (2H, m), 4.39-4.48 (1H, m).

Hide Experimental Procedure

Chevron Chemical Company LLC

Patent: US6165236 A1, 2000 ; Title/Abstract Full Text Show Details

2:Preparation of STR19

Example 2 Preparation of STR19 A solution of 26.4 grams of the product from example 1 in 100 ml of ethyl acetate and 100 mL of toluene containing 3.0 grams of 10percent palladium on charcoal was hydrogenated at 50 psi for 119 hours on a Parr low-pressure hydrogenator. Catalyst filtration and removal of the solvent in vacuo yielded the desired piperidine as a light brown oil. 1 H NMR (CDCl3 /D2 O) δ 7.05-7.25 (m, 2H), 6.75-6.9 (m, 2H), 4.85 (m, 1H), 2.75-4.0 (m, 65H), 0.7-1.8 (m, 129H).

Hide Experimental Procedure

Sterling Winthrop Inc.

Patent: US5242924 A1, 1993 ; Title/Abstract Full Text Show Details

B:METHOD B

METHOD B Compounds of formula I can also be prepared by reacting halopyridazine VI with the piperidine VII STR12 in the presence of DIPEA (diisopropylethylamine) and a noninteracting solvent as described above for the preparation of intermediate IV. Intermediate VII is prepared by reacting phenol III with a 4-hydroxypiperidine or 4-(hydroxyalkyl)piperidine in the presence of DEAD and triphenylphosphine as described above for the preparation of compounds of formula I.

Hide Experimental Procedure

Pfizer Inc.

Patent: US5442044 A1, 1995 ; Title/Abstract Full Text Show Details

73:

Using the procedure of Example 6, substituting SMeCys for OMeSer, the appropriate statine ester (Example 59) for nor CSta isopropyl ester and, in Step E, piperidine for dimethylamine, the following analogs were synthesised:

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

1.e:3-[2-[1-(Phenylmethyl)-4-piperidinyl]ethyl]-1, 2-benzisoxazole maleate STR15 a) 1,4-Piperidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, 4-ethyl ester.

e) 3-[2-[1-(Phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole maleate. Trifluoroacetic acid (TFA) (7 mL) was added dropwise to a cold (0° C.) solution of the piperidine formed in step d (0.50 g, 1.51 mmol) in methylene chloride (7 mL). The resulting solution was stirred at 0° C. for 30 min. Volatiles were removed under reduced pressure and excess TFA was removed by concentrating from toluene twice.

Hide Experimental Procedure

1.h:EXAMPLE 1

Zeneca Limited

Patent: US5559131 A1, 1996 ; Title/Abstract Full Text Show Details

h. N-[4-(4-tert-Butoxycarbonylaminopiperidino)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide. To a solution of 4-tert-butoxycarbonylaminopiperidine (5.4 g) in methanol (70 mL) was added acetic acid (1.5 mL) and the above aldehyde (6.3 g) in methanol (30 mL). The resulting solution was allowed to stir for 2 minutes. Sodium cyanoborohydride (1.7 g) in methanol (10 mL) was added, and the mixture was allowed to stir overnight. The mixture was neutralized with saturated aqueous sodium bicarbonate, stirred for 30 minutes, diluted with water, and extracted with dichloromethane. The organic layer was dried and evaporated to give the piperidine (6.7 g) as a white foamy solid; MS: m/z-534(M+1); Analysis for C28 H37 Cl2 N3 O3.0.18 CH2 Cl2: Calculated: C, 61.56; H, 6.84; N, 7.64; Found: C, 61.69; H, 6.77; N, 7.63. i.

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

10.c:c

c 6-Benzenesulfonamide-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole fumarate Trimethylsilyl trifluoromethanesulfonate (1.30 mL, 6.76 mmol) was added dropwise to a cold (0° C.) solution of the piperidine formed in step b (0.819 g, 1.69 mmol) and 2,6-lutidine (0.590 mL, 5.07 mmol) in CH2 Cl2 (17 mL).

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

11.c:c

c 6-(4-Morpholinyl)-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole Trifluoroacetic acid (TFA) (5 mL) was added to a cold (0° C.) solution of the piperidine formed in step b (0.40 g, 0.96 mmol) and thioanisole (1.13 mL, 9.60 mmol) in CH2 Cl2 (10 mL).

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

12.f:f

f 5,7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[4,5-f]-1,2-benzisoxazol-6-one maleate Trifluoroacetic acid (TFA) (3.3 mL) was added dropwise to a cold (0° C.) solution of the piperidine formed in step e (0.50 g, 1.30 mmol) in CH2 Cl2 (13 mL). After 30 min, the mixture was concentrated and excess TFA was removed by concentrating from toluene (2 to 3 times).

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

13.b:b

b 1-[2-[1-(Phenylmethyl)-4-piperidinyl]ethyl]-isoquinoline maleate The procedure described in Example 1e was followed using the piperidine formed in step a (0.713 g, 2.10 mmol) and TFA (7 mL) in CH2 Cl2 (14 mL), and triethylamine (2.9 mL, 21.0 mmol) and benzyl bromide (0.275 mL, 2.31 mmol) in CH2 Cl2 (60 mL). After purification (CH2 Cl2 -->5percent MeOH/CH2 Cl2), the title compound (free base) (0.26 g, 38percent) was obtained as a pale yellow oil.

Hide Experimental Procedure

Zeneca Limited

Patent: US5589489 A1, 1996 ; Title/Abstract Full Text Show Details

13.d:3-[1-(3,4-Dichlorophenyl)-3-(4-(2-methoxyphenyl)piperidino)propyl]-2-methyl-2,3 -dihydroisoindol-1-one hydrochloride

A solution of 1-benzyloxycarbonyl-4-(2-methoxyphenyl)piperidine (0.67 g) in ethanol (10 mL) was treated with cyclohexene (4.2 mL) followed by 10percent palladium on carbon (0.13 g). After heating to reflux for 2 hours, the reaction mixture was cooled to room temperature, diluted with ether and extracted with 1N hydrochloric acid. The aqueous layer was made basic with sodium bicarbonate and extracted with dichloromethane. The organic layers were dried over anhydrous sodium sulfate and evaporated to afford the piperidine (0.2 g); NMR (CDCl3): 1.60 (d of q,2, J1 =12, J2 =4), 1.73-1.82 (broad,2), 2.74-2.83 (d of t,2, J1 =12, J2 =2), 3.02-3.2 (m,3), 3.82 (s,3), 6.85 (d,1, J=8), 6.9 (m,1), (7.157.26 (m,2); MS: m/z=192(M+1). This material was used in the next step without further purification.

Hide Experimental Procedure

Zeneca Limited

Patent: US5589489 A1, 1996 ; Title/Abstract Full Text Show Details

14.c:3-[1-(3,4-Dichlorophenyl)-3-(4-(2-hydroxyphenyl)piperidino)propyl]-2-methyl-2,3-dihydroisoindol-1-one hydrochloride

1-Benzyloxycarbonyl-4-hydroxy-4-(2-benzyloxyphenyl)piperidine was subjected to a procedure similar to that described in Example 13 sub-part c. The resulting product was chromatographed, with hexane:ethyl acetate (3:1) as the eluent, to give the piperidine (1.67 g, contaminated with an impurity); NMR (CDCl3): 1.60-1.64 (m,2), 1.84 (broad,2), 2.89 (broad,2), 3.15-3.2 (m,1), 4.31 (s,2), 5.09 (d,2, J=7), 5.17 (d,2), 6.91-7.15 (m,2), 7.17-7.21 (m,2), 7.25-7.41 (m,10); MS: m/z=402(M+1). This material was used in the next step without any further purification.

Hide Experimental Procedure

Zeneca Limited

Patent: US5589489 A1, 1996 ; Title/Abstract Full Text Show Details

16.h:3-[1-(3,4-Dichlorophenyl)-3-(4-(2-oxoperhydropyrimidine-1-yl)piperidino)propyl]-6-methoxy-2-methyl-2,3-dihydroisoindol-1-one hydrochloride

1-Benzyloxycarbonyl-4-(2-oxoperhydropyrimidin-1-yl)piperidine was treated with trifluoroacetic acid using a procedure similar to that described in Example 66 sub-part h. The reaction product was purified by chromatography to give the piperidine.

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

20.b:b

b 3-[(1-Phenylmethyl-4-piperidyl)methoxy]-1,2-benzisoxazole fumarate Trifluoroacetic acid (TFA) (10 mL) was added dropwise to a solution of piperidine formed in step a (0.827 g, 2.49 mmol) in CH2 Cl2 (25 mL) at 0° C. The resulting mixture was stirred at 0° C. for 20 minutes. The mixture was concentrated, and excess TFA was removed by concentrating from toluene. The residue was partitioned between CH2 Cl2 and saturated NaHCO3.

Hide Experimental Procedure

Takeda Chemical Industries, Ltd.

Patent: US5538998 A1, 1996 ; Title/Abstract Full Text Show Details

21:1-(3-chloropropioloyl)piperidine

EXAMPLE 21 1-(3-chloropropioloyl)piperidine By a procedure analogous to Example 1, 2.20 g of 1-(3-chloropropioloyl)piperidine was obtained as a colorless oil from 3.50 g of 1-propioloylpiperidine 1 H-NMR (CDCl ): δ1.53-1.72 (m, 6H), 3.56 (t, 2H), 3.67 (t, 2H) 3 Elemental Analysis (percent): Calculated for C8 H10NOCl: C, 55.90; H, 5.87; N, 8.16 Found: C, 55.10; H, 5.87; N, 7.93

Hide Experimental Procedure

Zeneca Limited

Patent: US5589489 A1, 1996 ; Title/Abstract Full Text Show Details

26.j:3-[1-(3,4-Dichlorophenyl)-3-(4-methylaminocarbonyl)-4-(2-oxopiperidino)piperidino)propyl]-2-methyl-2,3-dihydro-6-methoxyisoindol-1-one hydrochloride

1-Benzyloxycarbonyl-4-(methylaminocarbonyl)-4-(2-oxoperhydropyrimidin-1-yl)piperidine was subjected to a procedure similar to that in Example 10 sub-part c. to give the piperidine; MS: m/z=241(M+1); NMR (CD3 OD): 3.41 (m,2), 3.19 (m,2), 3.05 (m,2), 2.89 (m,2), 2.69 (s,3), 2.16 (m,2), 2.00 (m,4).

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US5492920 A1, 1996 ; Title/Abstract Full Text Show Details

37:EXAMPLE 37 STR109

EXAMPLE 37 STR109 To a stirred solution of 5.0 g of the piperidine intermediate prepared in Example 1 Step B was added 5 mL of triethylamine at 0° C. and 2.8 mL of CBZ-Cl. The reaction was allowed to warm up to Rt and stir overnight. The reaction mixture was poured into aqueous ammonium chloride solution and extracted with CH2 Cl2. The organic layer was washed with 0.50N HCl solution, dried over MgSO4 and concentrated. This crude residue was dissolved in 25 mL of methanol-water and 3 eq. of sodium hydroxide was added and stirred for 2 h. The reaction mixture was acidified to pH=2 with 2N HCl and extracted with EtOAc. The combined organics were washed with brine, dried over Na2 SO4 and concentrated to give the acid as a foam. STR110 To a solution of 0.225 g of the above acid intermediate in 10 mL of CH2 Cl2 was added 0.12 g of benzenesulfonamide, 0.093 g of DMAP and 0.164 g of EDC and stirred overnight. The reaction mixture was washed with 0.50N HCl (2*10 mL), dried over Na2 SO4 and concentrated. The crude residue was dissolved in 10 mL of methanol and 0.10 g of 10percent Pd/C and hydrogenated at 40psi overnight. The catalyst was filtered off through a pad of celite and the filtrate was concentrated to provide the piperidine that was used without purification. The piperidine intermediate was now coupled to Intermediate 3 and deprotected with HCl/EtOAC as described above to give the title compound as a white solid. FAB MS m/e cacl. (for C35 H44 N4 O5 S) 632; found 633.1 (m+1)

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US5492920 A1, 1996 ; Title/Abstract Full Text Show Details

40:EXAMPLE 40 STR116

EXAMPLE 40 STR116 This intermediate was prepared in an analogous manner to the BOC material prepared in Step B of Example 38. STR117 To a stirred solution of 1.0 g of the nitrile from Step A in 10 mL of dry ethanol at 0° C. was bubbled in HCl(gas) for 1 h. The reaction was capped and stored in the freezer overnight. The excess HCl(gas) was removed by bubbling N2 gas for 1 h and ether was added to induce precipitation of the imino-ether intermediate, but only an oily material formed. Hence, the solvents were removed on the rotary evaporator and the gummy residue was dissolved in CH2 Cl2 and evaporated twice. Ether was now added and this provided the iminoether hydrochloride as a foam. To 0.20 g of the above intermediate in 5 mL of dichloroethane was added 0.073 mL of diisopropylethylamine and 0.030 g of formylhydrazine and stirred at room temperature overnight. The reaction mixture was poured into water and extracted with CH2 Cl2. The combined organics were washed with brine, dried over Na2 SO4 and concentrated. The residue thereby obtained was dissolved in 5 mL of xylenes and heated at reflux for several hours. The reaction mixture was cooled to room temperature and the xylenes were evaporated. The residue was hydrogenated for 2 h in 2 mL of methanol and 40 mg of 20percent palladium hydroxide catalyst. The piperidine thereby obtained was coupled with Intermediate 3 under the standard EDC/HOBT conditions described earlier.

Hide Experimental Procedure

Takeda Chemical Industries, Ltd.

Patent: US5538998 A1, 1996 ; Title/Abstract Full Text Show Details

46:1-(3-bromopropioloyl)piperidine

EXAMPLE 46 1-(3-bromopropioloyl)piperidine By a procedure analogous to Example 29, 2.35 g of 1-(3-bromopropioloyl)piperidine was obtained colorless crystals from 3.00 g of 1-propioloylpiperidine. Melting Point: 66.5°-67.5° C. 1 H-NMR (CDCl ): δ1.50-1.73 (m, 6H), 3.56 (t, 2H), 3.68 (t, 2H) 3 Elemental Analysis (percent): Calculated for C8 H10 NOBr: C, 44.47; H, 4.66; N, 6.48 Found: C, 44.18; H, 4.66; N, 6.49

Hide Experimental Procedure

Zeneca Limited

Patent: US5589489 A1, 1996 ; Title/Abstract Full Text Show Details

66.h:EXAMPLE 66

A solution of 1-benzyloxycarbonyl-4-(2-methylsulfinylphenyl)piperidine (1.66 g) in 8 mL of trifluoroacetic acid was heated to reflux for 45 minutes. The reaction mixture was evaporated and the residue was treated with toluene. Upon evaporating the solvent, the residue was treated with an additional portion of toluene and the process was repeated. The final residue was dried under reduced pressure and purified by chromatography, with dichloromethane:methanol:triethylamine (19:1:1) as the eluent, to give the piperidine (0.87 g); MS: 224; NMR: 1.6-2.4 (m, 4), 2.7 (two peaks,3), 2.9-3.2 (m,3), 3.3-3.5 (m,2), 5.3-5.7 (broad, 1), 7.4-7.5 (m,3), 7.9-8.0 (m, 1).

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

7.b:b

b 6-Acetamido-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2 -benzisoxazole fumarate Trifluoroacetic acid (TFA) (4 mL) was added dropwise to a cold (0° C.) solution of the piperidine formed in step a (0.40 g, 1.03 mmol) in CH2 Cl2 (8 mL). The resulting solution was stirred at 0° C. for 30 min. Volatiles were removed under reduced pressure and excess TFA was removed by concentrating from toluene twice.

Hide Experimental Procedure

Pfizer Inc.

Patent: US5538984 A1, 1996 ; Title/Abstract Full Text Show Details

9.c:c

c 6-Benzamide-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazolemaleate Trifluoroacetic acid (TFA) (8.4 mL) was added dropwise to a cold (0° C.) solution of the piperidine formed in step b (0.70 g, 1.56 mmol) in CH2 Cl2 (10 mL). The resulting solution was stirred at 0° C. for 30 min. Volatiles were removed under reduced pressure and excess TFA was removed by concentrating from toluene twice.

Hide Experimental Procedure

Adir Et Compagnie

Patent: US5599812 A1, 1997 ; Title/Abstract Full Text Show Details

More particularly, the present invention relates to the compounds of formula (I): STR2 in which: R1 represents a group of formula: STR3 in which R2 and R3 form, with the nitrogen atom which carries them, a group chosen from: piperazine, piperidine, pyrrolidine, morpholine, tetrahydropyridine, thiomorpholine,

Hide Experimental Procedure

Zeneca Limited

Patent: US5654299 A1, 1997 ; Title/Abstract Full Text Show Details

1.h:h.

A solution of 4-hydroxy-4-phenyl-piperidine (1.99 g) in methanol (20 mL) was cooled to 0° C. and the pH was adjusted to 8 by adding acetic acid. To this solution was added N-[2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methylbenzamide (3.57 g) in methanol (20 mL), and the resulting reaction mixture was treated with sodium cyanoborohydride (0.765 g). Upon warming to the room temperature, the reaction mixture was stirred for 16 hours and treated with saturated sodium bicarbonate solution. The solution was extracted with dichloromethane, dried (anhydrous sodium sulfate) and evaporated. The resulting material was purified by chromatography, with dichloromethane:methanol (90:10) as the eluent, to give the piperidine (2.42 g); NMR (CDCl3): 1.5-2.5 (m, 10), 2.68 (broad, 4), 3.47 (s,3), 3.5-3.57 (m, 1), 6.8-7.5 (m, 13); MS: m/z=511(M+1). This material was used in the next step without further purification.

Hide Experimental Procedure

Zeneca Limited

Patent: US5654299 A1, 1997 ; Title/Abstract Full Text Show Details

2.d:d.

A solution of 1-benzyloxycarbonyl-4-(2-methoxyphenyl)piperidine (0.67 g) in ethanol (10 mL) was treated with cyclohexene (4.2 mL) followed by 10percent palladium on carbon (0.13 g). After heating to reflux for 2 hours, the reaction mixture was cooled to room temperature, diluted with ether and extracted with 1N hydrochloric acid. The aqueous layer was made basic with sodium bicarbonate and extracted with dichloromethane. The organic layers were dried over anhydrous sodium sulfate and evaporated to afford the piperidine (0.2 g); NMR (CDCl3): 1.60 (d of q, 2, J1 =12, J2 =4), 1.73-1.82 (broad, 2), 2.74-2.83 (d of t, 2, J1 =12, J2 =2), 3.02-3.2 (m, 3), 3.82 (s,3), 6.85 (d, 1, J=8), 6.9 (m, 1), 7.157.26 (m, 2); MS: m/z=192(M+1). This material was used in the next step without further purification.

Hide Experimental Procedure

Zeneca Limited

Patent: US5635509 A1, 1997 ; Title/Abstract Full Text Show Details

28.j:5-[(1R,2S)-2-(3,4-dichlorophenyl)-1-hydroxy-4-[4-(methylaminocarbonyl)-4-(2-oxopiperidino)piperidino]butyl]-1-phenyl-1,2,3-(1H)-triazole

1-Benzyloxycarbonyl-4-(methylaminocarbonyl)-4-(2-oxopiperidino)piperidine was hydrogenated over 20percent palladium hydroxide on carbon in ethanol overnight. The mixture was filtered through diatomaceous earth, and the filtrate was evaporated to give the piperidine; MS: m/z=240(M+1); NMR (CD3 OD): 3.45 (m,2), 3.10 (m,2), 2.96 (m,2), 2.68 (m,3), 2.32 (m,2), 2.22 (m,2), 1.90 (m,4), 1.75 (m,2).

Hide Experimental Procedure

Elf Sanofi

Patent: US5674881 A1, 1997 ; Title/Abstract Full Text Show Details

2:(Compound 2) STR64

EXAMPLE 2 (Compound 2) STR64 0.3 g of 1-[3-(3,4-dichlorophenyl)-4-(4-fluoro-naphthoylamino)butyl]-4-benzyl-N(e)-methyl-1-piperidinium iodide, in which the methyl in the 1-position on the nitrogen of the piperidine is in the equatorial position, is obtained by following the procedure described above in Example 1 and collecting the fraction eluted second. M.p.=120°-122° C. 1 H NMR: 7 H between 1.3 and 2.4 (2CH and CH piperidine, CH β); 14 H between 2.45 and 4 (2CH N piperidine, CH Ar, N--CH , N--CH , CH Ar', CH --NH); 14 H between 7 and 8.3 (all the aromatic H); 1 H at 8.6 (NM); DMSO at 2.49. 2 2 2 2 3 2 2

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US5721251 A1, 1998 ; Title/Abstract Full Text Show Details

37:EXAMPLE 37 STR112

EXAMPLE 37 STR112 To a stirred solution of 5.0 g of the piperidine intermediate prepared in Example 1 Step B was added 5 mL of triethylamine at 0° C. and 2.8 mL of CBZ-Cl.

The reaction was allowed to warm up to Rt and stir overnight. The reaction mixture was poured into aqueous ammonium chloride solution and extracted with CH2 Cl2. The organic layer was washed with 0.50N HCl solution, dried over MgSO4 and concentrated. This crude residue was dissolved in 25 mL of methanol-water and 3 eq. of sodium hydroxide was added and stirred for 2 h. The reaction mixture was acidified to pH=2 with 2N HCl and extracted with EtOAc. The combined organics were washed with brine, dried over Na2 SO4 and concentrated to give the acid as a foam. STR113 To a solution of 0.225 g of the above acid intermediate in mL of CH2 Cl2 was added 0.12 g of benzenesulfonamide, 0.093 g of DMAP and 0.164 g of EDC and stirred overnight. The reaction mixture was washed with 0.50N HCl (2*10 mL), dried over Na2 SO4 and concentrated. The crude residue was dissolved in 10 mL of methanol and 0.10 g of 10percent Pd/C and hydrogenated at 40 psi overnight. The catalyst was filtered off through a pad of celite and the filtrate was concentrated to provide the piperidine that was used without purification. The piperidine intermediate was now coupled to Intermediate 3 and deprotected with HCl/EtOAC as described above to give the title compound as a white solid. FAB MS m/e cacl. (for C35 H44 N4 O5 S) 632; found 633.1 (m+1)

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US5721251 A1, 1998 ; Title/Abstract Full Text Show Details

40:EXAMPLE 40 STR119

EXAMPLE 40 STR119 This intermediate was prepared in an analogous manner to the BOC material prepared in Step B of Example 38. STR120 To a stirred solution of 1.0 g of the nitrile from Step A in mL of dry ethanol at 0° C. was bubbled in HCl(gas) for 1 h. The reaction was capped and stored in the freezer overnight. The excess HCl(gas) was removed by bubbling N2 gas for 1 h and ether was added to induce precipitation of the imino-ether intermediate, but only an oily material formed. Hence, the solvents were removed on the rotary evaporator and the gummy residue was dissolved in CH2 Cl2 and evaporated twice. Ether was now added and this provided the iminoether hydrochloride as a foam. To 0.20 g of the above intermediate in 5 mL of dichloroethane was added 0.073 mL of diisopropylethylamine and 0.030 g of formylhydrazine and stirred at room temperature overnight. The reaction mixture was poured into water and extracted with CH2 Cl2. The combined organics were washed with brine, dried over Na2 SO4 and concentrated. The residue thereby obtained was dissolved in 5 mL of xylenes and heated at reflux for several hours. The reaction mixture was cooled to room temperature and the xylenes were evaporated. The residue was hydrogenated for 2 h in 2 mL of methanol and 40mg of 20percent palladium hydroxide catalyst. The piperidine thereby obtained was coupled with Intermediate 3 under the standard EDC/HOBT conditions described earlier.

Hide Experimental Procedure

Zeneca Limited

Patent: US5654299 A1, 1997 ; Title/Abstract Full Text Show Details

6.c:c.

1-Benzyloxycarbonyl-4-hydroxy-4-(2-benzyloxyphenyl)piperidine was subjected to a procedure similar to that described in Example 2.c. The resulting product was chromatographed, with hexane:ethyl acetate (3:1) as the eluent, to give the piperidine (1.67 g, contaminated with an impurity); NMR (CDCl3): 1.60-1.64 (m, 2), 1.84 (broad, 2), 2.89 (broad, 2), 3.15-3.2 (m, 1), 4.31 (s,2), 5.09 (d, 2, J=7), 5.17 (d, 2), 6.91-7.15 (m, 2), 7.17-7.21 (m, 2), 7.25-7.41 (m, 10); MS: m/z=402(M+1). This material was used in the next step without any further purification.

Hide Experimental Procedure

Elf Sanofi

Patent: US5674881 A1, 1997 ; Title/Abstract Full Text Show Details

7:(Compound 7) STR69

EXAMPLE 7 (Compound 7) STR69 The quaternary salt of 1-[3-(3,4-dichlorophenyl)-4-(N-methyl-2-thenoylamino)butyl]-4-hydroxy-4-phenyl-N(e)-methyl-1-piperidinium (-) iodide, in which the methyl in the 1-position on the nitrogen of the piperidine is in the equatorial position, is obtained by following the procedure according to Example 6 and collecting the compound eluted second. M.p.=130° C.

Hide Experimental Procedure

Zeneca Limited

Patent: US5654299 A1, 1997 ; Title/Abstract Full Text Show Details

9.i:i.

A solution of 1-benzyloxycarbonyl-4-(3-pyridyl)-1,2,3,4-tetrahydropyridine (0.714 in ethanol (50 mL) was treated with 10percent palladium on carbon (0.1 g) and hydrogenated under a hydrogen atmosphere at room temperature and 3.44 bar for 16 hours. The reaction mixture was filtered through diatomaceous earth to remove the catalyst, and the resulting filtrate was evaporated to afford the piperidine (0.393 g); NMR (CDCl3): 1.7 (m, 4), 2.8 (m, 4), 3.2 (m, 2), 7.3 (m, 1), 7.5 (m, 1), 8.5 (m, 2); MS: m/z=162(M+1).

Hide Experimental Procedure

Adir Et Compagnie

Patent: US5599812 A1, 1997 ; Title/Abstract Full Text Show Details

A compound which is selected from those of formula (I): STR30 in which: R1 represents a group of formula: STR31 in which R2 and R3 form, with the nitrogen atom which carries them, a group chosen from: piperazine, piperidine, pyrrolidine, morpholine, tetrahydropyridine, thiomorpholine,

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US5830433 A1, 1998 ; Title/Abstract Full Text Show Details

3:1,2-Dihydro-1-benzyloxycarbonyl-spiro[3H-indole-3,4'-piperdine] hydrochloride

EXAMPLE 3 1,2-Dihydro-1-benzyloxycarbonyl-spiro[3H-indole-3,4'-piperdine] hydrochloride To a solution of 99g (0.489 mol) of N'-methyl spiro(indoline-3,4'-piperidine) (i.e. 1'-methyl-1,2-dihydro-spiro[3H-indole-3,4'-piperdine]) (prepared according to the method of Ong et al. J. Med. Chem. 1983, 26, 981-986) in 1 L of dichloromethane was added 82 mL (0.588 mol) of triethylamine and the reaction was cooled to 0C. CBZ-Cl (77 mL; 0.539 mol) was added in a dropwise manner over 30 min and the temperature was maintained below 10° C. After 2 h an additional 19 mL of triethylamine and 5 mL of CBZ-Cl were added and stirred for 2 h. Analysis of the reaction mixture showed a small amount of the starting material and so additional 19 mL of triethylamine and 15 mL of CBZ-Cl were added and stirred for 2 h. The volatiles were removed on the rotary evaporator and the residue was taken up in ether (1000 mL) and washed with 500 mL of saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with 500 mL of ether and the combined organics were washed with 500 mL of saturated aqueous sodium bicarbonate solution, 500 mL of brine, dried over anhydrous magnesium sulfate and concentrated. The residue was chromatographed on 2 kg of silica gel and eluted with 2.5percent methanol/CH2 Cl2 with increasing polarity to 5percent methanol/CH2 Cl2 to give 117 g (71percent) of the desired material as a yellow oil. To a solution of 117 g (0.348 mol) of the above N-methyl spiro-piperidine in 800 mL of 1,2-dichloroethane at 0° C. was added 50 mL (0.463 mL) of 1-chloroethyl chloroformate over 20 min. and the reaction mixture was heated at reflux for 1 h. The reaction mixture was cooled, concentrated to approximately 1/4th of the original volume, diluted with 700mL of methanol and refluxed for 1.5 h. The rection mixture was concentrated to dryness, the residue was washed with cold methanol, followed by ether and dried under vacuum to 75.3 g of a brown solid. The filtrate was concentrated to give a brown foam (58 g). The solid and the foam were taken up in dichloromethane and washed with 2.5N sodium hydroxide till basic. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated to provide a residue that was chromatographed on 2 kg of silica gel. Elution with 20 liters of 5percent methanol/CH2 Cl2 followed by 20 liters of 90/10/1 methanol/CH2 Cl2 /NH4 OH provided 91.26 g of the piperidine and 14.84 g of recovered starting material. 37.0 g (87.3%)

Hide Experimental Procedure

Bristol-Myers Squibb Company

Patent: US5158958 A1, 1992 ; Title/Abstract Full Text Show Details

3:piperidine (5)

piperidine (5) Ethyl chloroformate (35.2 g, 0.32 mol) was added dropwise over about 30 minutes to a stirred and heated (90° C.) solution of 1-methyl-4-(ethoxycarbonyl mercapto)piperidine (33.0 g, 0.16 mol) in dry toluene (35 mL). The resultant mixture was then heated to about 100°-110° C. for about 2 hours. After this period additional ethyl chloroformate (12 mL) was added dropwide and then continued to heat at about 100°-110° C. for additional 3 hours. Reaction mixture was allowed to cool to room temperature and stand overnight. The resultant suspension was filtered off and the filtrate was washed with toluene. Combined filtrate and washings were rotary evaporated to remove the toluene and then residue was distilled in vacuo to give 37.0 g (87.3percent) of pure 5: bp 116°-118° C./0.01 torr; IR (Film, cm-1) 1702, 1252, 1144, 1388; 1 H NMR (300 MHz, CDCl3) δ

1.18 (3H, t, J=7.1Hz), 1.23 (3H, t, J=7.1H), 1.52 (2H, m), 1.95 (2H, m), 3.02 (2H, m), 3.40 (1H, m), 3.90 (2H, m), 4.03 (2H, q, J=7.1Hz), 4.19 (2H, q, J=7.1Hz); 13 C NMR (75 MHz, CDCl3) δ 14.44, 14.84, 32.13, 41.98, 43.49, 61.52, 63.63, 155.50, 170.14; MS m/e 262 (MH+).

Hide Experimental Procedure

The DuPont Merck Pharmaceutical Company

Patent: US5849736 A1, 1998 ; Title/Abstract Full Text Show Details

D:Part D

To a solution of t-butyl N2 -3-methylphenylsulfonyl-N3 -[(3-(N-t-butyloxycarbonyl-2-piperidin-4-yl)ethyl)isoxazolin-5(R,S)-ylacetyl]-(S)-2,3-diaminopropionate (261 mg, 0.410 mmol) in CH2 Cl2 (2 mL) was added TFA (2 mL, 26 mmol). After 2 h at room temperature, the solution was concentrated in vacuo and the residue triturated with ether (3*5 mL). The resulting white powder was purified using reverse phase HPLC, giving 202 mg (83percent) of the desired piperidine; MS (ESI, e/z, relative intensity): 481 (M+H)+, 100percent.

Hide Experimental Procedure

BASF Aktiengesellschaft

Patent: US5817871 A1, 1998 ; Title/Abstract Full Text Show Details

Preferred examples of cyclic amines III are: pyrrolidine, morpholine and piperidine, dihydropyrrole and tetrahydropyrrole.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US5767118 A1, 1998 ;

Title/Abstract Full Text Show Details

Step E

STR49 To a solution of 0.87 g of the intermediate prepared in Step A in 3 mL of CH2 Cl2 was added 1 mL of TFA and stirred at RT for 30 min. The reaction mixture was evaporated to dryness, basified with 10percent aqueous sodium carbonate solution, and extracted with CH2 Cl2. The combined organics were dried over K2 CO3, filtered and concentrated to give the piperidine that was elaborated to the desired compound with coupling it with Intermediate 1 under the EDC/HOBT conditions as described previously. 1 H NMR (CDCl , 400 MHz; mixture of rotamers) 8.62 and 8.50 (2 singlets, 1H), 7.83 and 7.58 (2 doublets, 1H), 7.35-6.60 (m, 8H), 5.37-5.15 (m, 1H), 5.09 and 5.00 (2 bs, 1H), 4.73 and 4.65 (2bd, 1H), 4.60-4.50 (m, 2H), 4.42-4.00 (m, 3H), 3.63 and 3.52 (2 bd, 1H), 3.303 3.05 (m, 2H), 2.80-1.95 (m, 4H), 1.83-1.60 (m, 1H), 1.51, 1.50 and 1.48 (3s, 6H), 1.41 (s, 9H), 1.23 (2q, 3H), 1.05 and 1.66 (m, 1H).

Hide Experimental Procedure

Bayer Aktiengesellschaft

Patent: US4920136 A1, 1990 ; Title/Abstract Full Text Show Details

The substituents R6 and R7 preferably have the meanings indicated hereinbefore as preferred for the compounds of the formula I. The following specific compounds of the formula III may be mentioned: Ammonia, methylamine, dimethylamine, ... tert.-butylamine, cyclopentylamine, cyclohexylamine, benzylamine, piperidine, pyrrolidine, morpholine and 2-aminopyridine.

Hide Experimental Procedure

Bayer Aktiengesellschaft

Patent: US4920136 A1, 1990 ; Title/Abstract Full Text Show Details

The following specific amines of the formula III may be mentioned: Ammonia, methylamine, dimethylamine, ... i-butylamine, tert.-butylamine, cyclopentylamine, cyclohexylamine, piperidine, pyrrolidine, pyrrole and morpholine.

Hide Experimental Procedure

Beecham Pharmaceuticals

Patent: US5039803 A1, 1991 ; Title/Abstract Full Text Show Details

4:(+-)-cis-4-p-Fluorophenyl-3-hydroxymethyl-1-methylpiperidine STR13 The quarternary salt (5; 1.45 g; 0.005 moles) in ethanol (50 ml) was hydrogenated over Adam's catalyst (150 mg) at atmospheric pressure and room temperature for 4 hours.

Column chromatography of the crude product (Al2 O3: Activity II; EtOAc) afforded the desired piperidine (6) as a pale yellow solid (0.4 g; 37percent). m.p.: 87-9° C. nmr (CDCl3) δ7.30-6.95, (m), 4H δ3.70-3.50, (m), 2H δ3.20-3.05, (m), 2H δ2.90-2.80, (m), 1H δ2.60-2.40, (m), 2H δ2.30, (s), 3H δ2.20-2.05, (m), 1H δ1.80-1.70, (m), 2H

Hide Experimental Procedure

Du Pont Merck Pharmaceutical Company

Patent: US5116846 A1, 1992 ; Title/Abstract Full Text Show Details

1.A:Part A:

Part A: 1-Benzyl-4-(methoxymethylidene) piperidine A solution of di-isopropylamine (11.1 g, 15.4 mL, 110 mmol) in anhydrous tetrahydrofuran (100 mL) was cooled to 0° C. under a nitrogen atmosphere. A solution of n-butyl lithium in hexanes (2.5 M, 44 mL, 110 mmol) was added dropwise with stirring. The pale yellow solution was stirred for 15 minutes at 0° C., then transferred via cannula to a suspension of methoxymethyl-triphenylphosphonium chloride (37.7 g, 110 mmol) in dry tetrahydrofuran (300 mL) stirred at -20° C. After 30 minutes, the reaction mixture was cooled to -40° C. and a solution of 1-benzylpiperid-4-one (18.9 g, 18.5 mL, 100 mmol) in anhydrous tetrahydrofuran (100 mL) was added dropwise over 15 minutes.

The reaction mixture was warmed gradually to ambient temperature over 23 h. The reaction mixture was then poured onto water, mixed and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and filtered; solvent was removed in vacuo. Column chromatography (ethyl acetate) gave starting piperidine (Rf =0.7, 0.5 g) and the product (Rf =0.51, 11.6 g), an orange-yellow liquid:1 H-NMR:7.4-7.25(m,5H), 5.8(s,1H), 3.5(s,2H), 3.45(s,3H), 2.5-2.3(m,5H), 2.05(t,2H,J=7); MS:217.

Hide Experimental Procedure

Fisons Corporation

Patent: US5075317 A1, 1991 ; Title/Abstract Full Text Show Details

1:b)

piperidine Solid CNBr (1.39 g, 13.16 mmol) was added to a solution of the product of step a) (3.04 g, 11.24 mmol) in dichloromethane (55 ml) at 0° and stoppered. The reaction mixture was stirred at 0° for 2.5 hours. Evaporation and purification on a silica gel, eluding with MeOH/CH2 Cl2 gave the sub-title compound (1.5 g).

Hide Experimental Procedure

Sandoz, Inc.

Patent: US4582848 A1, 1986 ; Title/Abstract Full Text Show Details

(i) N,N-dimethyl-2-(5-methyl-3-phenyl-4-isoxazolyl)-3-indole glyoxamide, respectively. Following the procedure of Step A and using in place of the dimethylamine an equivalent amount of (j) pyrrolidine; (k) piperidine; or (l) morpholine,

Hide Experimental Procedure

Fisons Corporation

Patent: US5073560 A1, 1991 ; Title/Abstract Full Text Show Details

Particular rings that A-N(R2)-B, together with the carbon atom to which they are attached (hereinafter "ring A"), may represent include: piperidine, 1 -azabicyclo[2.2.2]octane (known also as quinuclidine), 1-azabicyclo[3.2.2]nonane, 1-azabicyclo[3.3.1]nonane, 1-azabicyclo[3.1.1]heptane, ...

Hide Experimental Procedure

Sumitomo Chemical Company, Limited

Patent: US4698421 A1, 1987 ; Title/Abstract Full Text Show Details

Examples of the aliphatic amines are: Methylamine ... N-Methylcyclohexylamine N-(2-Hydroxyethyl)-cyclohexylamine 3,3,5-Trimethylcyclohexylamine Morpholine Piperidine Pyrrolidine

Hide Experimental Procedure

Exemplary amines used in the final step of the process include the following. ... ethylpropylamine dipropylamine morpholine pyrrolidine piperidine

Eli Lilly and Company

Patent: US4264775 A1, 1981 ; Title/Abstract Full Text Show Details

Hide Experimental Procedure

Hoechst Aktiengesellschaft

Patent: US4755602 A1, 1988 ; Title/Abstract Full Text Show Details

Examples of compounds of the formula VI are: ... 2,3-dimethylcyclohexylamine, 2,6-dimethylmorpholine, methylcyclohexylamine, pyrrolidine, piperidine, 3,5,5-trimethylhexylamine, 2,2-dimethylpropylamine, di-n-octylamine, ...

Hide Experimental Procedure

Sandoz, Inc.

Patent: US4336378 A1, 1982 ; Title/Abstract Full Text Show Details

Also following the above procedure and using in place of dimethylamine an equivalent amount of (d) morpholine, (e) piperidine, or (f) N-methylpiperazine

Hide Experimental Procedure

Sandoz, Inc.

Patent: US4336379 A1, 1982 ; Title/Abstract Full Text Show Details

Also following the above procedure and using in place of dimethylamine an equivalent amount of: (n) diethylamine, (o) morpholine, (p) pyrrolidine, or (g) piperidine

Hide Experimental Procedure

Smith Kline and French Laboratories Limited

Patent: US4385058 A1, 1983 ; Title/Abstract Full Text Show Details

(i) Reaction of 4-(hydroxymethyl)pyridine with thionyl chloride gives 4-(chloromethyl)pyridine which is reacted with (a) dibutylamine (b) pyrrolidine (c) piperidine

Hide Experimental Procedure

Bristol-Myers Company

Patent: US4471122 A1, 1984 ; Title/Abstract Full Text Show Details

Bristol-Myers Company

Patent: US4510309 A1, 1985 ; Title/Abstract Full Text Show Details

The general procedure of Example 82 is repeated, except that the dimethylamine utilized therein is replaced by pyrrolidine, piperidine, morpholine, thiomorpholine, piperazine, N-acetylpiperazine, N-methylpiperazine, hexamethyleneimine and

Hide Experimental Procedure

Dr. Karl Thomae GmbH

Patent: US4550107 A1, 1985 ;

Title/Abstract Full Text Show Details

D.b:(b)

(b) 2-[(Diethylamino)methyl[piperidine dihydrochloride A solution of hydrogen chloride gas (122.4 g, 3.357 mol) in 2-propanol (687 ml) is introduced with stirring, into a solution of the crude 2-[(diethylamino)methyl[piperidine obtained n step (a) (259 g=1.521 mol) in 2-propanol (648 ml).

Hide Experimental Procedure

Ciba-Geigy Corporation

Patent: US4507236 A1, 1985 ; Title/Abstract Full Text Show Details

phenylhydrazine, ... N-ethyl-N-phenylamine, benzylamine, cyclohexylamine, morpholine, piperidine, toluidine, xylidine, chloroaniline, ...

Hide Experimental Procedure

A. H. Robins Company, Incorporated

Patent: US4826866 A1, 1989 ; Title/Abstract Full Text Show Details

Utilizing Method B and the procedure of Jensen, et al., Acta Chem. Scand., 22, 37 (1968) and reacting the following: (a) dimethylamine, ... (e) N-methylcyclopentylamine, (f) 1-phenylpiperazine, (g) 1-benzylpiperazine, (h) pyrrolidine, (i) piperidine, and (j) homopiperidine

Hide Experimental Procedure

SmithKline Corporation

Patent: US3933811 A1, 1976 ; Title/Abstract Full Text Show Details

By the procedure of Example I, using in place of morpholine, the following amines: pyrrolidine piperidine 1-methylpiperazine diethylamine

Hide Experimental Procedure

SmithKline Corporation

Patent: US3950522 A1, 1976 ; Title/Abstract Full Text Show Details

By the procedure of Example 3, using in place of morpholine, the following compounds: ... dibutylamine pyrrolidine piperidine N-methylpiperazine ...

Hide Experimental Procedure

Sumitomo Chemical Company, Limited

Patent: US4009278 A1, 1977 ; Title/Abstract Full Text Show Details

Typical examples of the N-phenylmaleimide and amine employed in the above-mentioned process are as set forth below, but it is needless to say that the scope of the present invention is not limited thereby. N-Phenylmaleimides: ... Di-iso-amylamine Dihexylamine Dicyclohexylamine Pyrrolidine Piperidine Morpholine

Hide Experimental Procedure

SmithKline Corporation

Patent: US3948892 A1, 1976 ; Title/Abstract Full Text Show Details

Similarly, using in place of diethylamine the following: piperidine pyrrolidine 1-methylpiperazine

Hide Experimental Procedure

SmithKline Corporation

Patent: US3933811 A1, 1976 ; Title/Abstract Full Text Show Details

By the procedure of Example 2, using in place of morpholine, the following amines: pyrrolidine piperidine 1-methylpiperazine diethylamine

Hide Experimental Procedure

SmithKline Corporation

Patent: US3933811 A1, 1976 ; Title/Abstract Full Text Show Details

By the same procedure, using the following compounds in place of pyrrolidine: dimethylamine diethylamine piperidine 1-methylpiperazine

Hide Experimental Procedure

Sandoz, Inc.

Patent: US4016170 A1, 1977 ; Title/Abstract Full Text Show Details

Following the above procedure and using in place of methyl amine, an equivalent amount of: a. concentrated ammonium hydroxide solution, b. isopropyl amine, c. pyrrolidine, d. piperidine, or e. morpholine,

Hide Experimental Procedure

Monsanto Company

Patent: US3965220 A1, 1976 ; Title/Abstract Full Text Show Details

The following list of illustrative compounds is therefore to be read in the light of the above teachings. Aliphatic and Alicyclic Amines methylamine n-butylamine tetramethylammonium chloride ... 1,3-di-4-piperidylpropane ethyleneimine

2-aminopyridine piperidine picoline 2-aminomethylpiperidine 1-furyl-2-aminopropane ...

Hide Experimental Procedure

Sandoz, Inc.

Patent: US4049813 A1, 1977 ; Title/Abstract Full Text Show Details

Again following the above procedure and using in place of dimethylamine an equivalent amount of f. methylamine, g. N-methyl-piperazine, h. piperidine, or i. morpholine

Hide Experimental Procedure

Sumitomo Chemical Company, Limited

Patent: US4055565 A1, 1977 ; Title/Abstract Full Text Show Details

Examples of secondary amines are as follows: Dimethylamine Diethylamine Diethanolamine Pyrrolidine Piperidine Morpholine N-methylaniline

Hide Experimental Procedure

Ciba-Geigy Corporation

Patent: US4189587 A1, 1980 ; Title/Abstract Full Text Show Details

Examples of the groups R4 and R5 when, together with the nitrogen atom to which they are attached, they form a heterocyclic ring are: pyrrolidine, piperidine, 2-methylpiperidine, 3-methylpiperidine, 4-methylpiperidine, 3,5-dimethylpiperidine, morpholine, piperazine and N-methylpiperazine.

Hide Experimental Procedure

Syntex (U.S.A.) Inc.

Patent: US4139626 A1, 1979 ; Title/Abstract Full Text Show Details

In similar manner, substituting: 4-methylpiperazine; piperidine; thiomorpholine; pyrrolidine; thiazolidine; 2,6-dimethylpiperidine; 2,6-dimethylmorpholine; 4-hydroxypiperidine; 2-methylpiperidine; ...

Hide Experimental Procedure

Petrolite Corporation

Patent: US4074999 A1, 1978 ; Title/Abstract Full Text Show Details

The following are illustrative examples of cyclic amines. Morpholine Piperidine Pyrrolidine Azetidine Thiomorpholine N-ethyl piperazine N-hydroxyethyl piperazine Hexahydroazepine

Hide Experimental Procedure

Sandoz Ltd.

Patent: US4108887 A1, 1978 ; Title/Abstract Full Text Show Details

EXAMPLE 2 STR26 100 parts of stilbene-4,4'-dialdehyde are heated with stirring at reflux with 150 parts of malonic acid monoethylester and 500 parts of dry pyridine and 0.5 parts of piperidine until the aldehyde has disappeared in the thin-layer chromatograph. Purification is carried out by recrystallisation from hydrocarbon mixture which boils at between 150° and 180°; melting point 240°-249°.

Hide Experimental Procedure

Sandoz, Inc.

Patent: US4219560 A1, 1980 ; Title/Abstract Full Text Show Details

Also following the above procedure and using in place of morpholine an equivalent amount of (e) ammonia, (f) dimethylamine, (g) piperidine, (h) N-methylpiperazine, or (i) pyrrolidine

Hide Experimental Procedure

NOVO NORDISK A/S

Patent: EP749423 B1, 2003 ; Title/Abstract Full Text Show Details

1:(3R,4R,5R)-3,4-Dihydroxy-5-hydroxymethylpiperidine hydrochloride:

If necessary, the piperidine could be chromatographed using ethanol/NH4OH (25percent aqueous) (10:1) to give the free piperidine. Analytical calculation for C6H13NO3: C: 48.97; H: 8.90; N: 9.52. Found: C: 48.46; H: 9.33; N: 9.17.

Hide Experimental Procedure

ELI LILLY AND COMPANY

Patent: EP825164 A2, 1998 ; Title/Abstract Full Text Show Details

Additional primary amines suitable for the process of the invention are those represented by the following formulae: where CBz is Benzyloxycarbonyl. Secondary Amine Reagents ... morpholine 2,6-dimethylmorpholine thiomorpholine 1,4-dioxa-8-azaspiro[4.5] decane piperidine ethyl pipecolinate

Hide Experimental Procedure

TEIJIN LIMITED

Patent: EP1179341 A1, 2002 ; Title/Abstract Full Text Show Details

[Examples 822 to 912] Solid-phase synthesis of 3-aminopyrrolidines

[Examples 822 to 912] Solid-phase synthesis of 3-aminopyrrolidines Diisopropylethylamine (3.6 mL) was added to a mixture of the corresponding carboxylic acid (1.6 mmol) with HBTU (1.6 mmol) and DMF (6 mL), and the resulting mixture was shaken for 2 minutes. A 4-[[N-(1-(9-fluorenylmethoxycarbonyl)pyrrolidin-3-yl)carbamoylmethyl]aminomethyl]-3-methoxyphenyloxymethyl-polystyrene (400 mg, 0.4 mmol) was added, and the obtained mixture was shaken for 1 hour and then filtered. The resin was washed with DMF and dichloromethane and dried. A mixture of the resulting resin with piperidine (3.2 mL) and DMF (12.8 mL) was shaken for 10 minutes and then filtered. The resin was washed with DMF and dichloromethane and dried.

Hide Experimental Procedure

PFIZER INC.

Patent: EP438233 A2, 1991 ; Title/Abstract Full Text Show Details

73:

Using the procedure of Example 6 , substituting SMeCys for OMeSer, the appropriate statine ester (Example 59) for nor CSta isopropyl ester and, in Step E, piperidine for dimethylamine, the following analogs were synthesised: 29.7 g (87%)

Hide Experimental Procedure

EGIS Gyogyszergyar

Patent: US5130487 A1, 1992 ; Title/Abstract Full Text Show Details

9:The process of Example 1 is followed except that piperidine (9.37 g; 0.11 mole) is used instead of diisopropyl amine.

The process of Example 1 is followed except that piperidine (9.37 g; 0.11 mole) is used instead of diisopropyl amine. Yield: 29.7 g (87percent). (E)-2-Butenedioate (2/1) Melting point: 167°`9° C. Analysis for formula C23 H32 N2 O4 (400.51): Calculated: C=68.97percent; H=8.05percent; N=7.00percent; Found: C=68.57percent; H=8.01percent; N=7.12percent.

Hide Experimental Procedure

Merck and Co., Inc.

Patent: US6329380 B1, 2001 ; Title/Abstract Full Text Show Details

40.C:Step C

Step C 2-[1-(1-Methanesulfonylpiperidin-3-yl)-ethylamino]-4-[5-N-(benzoyl)-aminobenzimidazol-1-yl]pyrimidine 2-[1-(1-benzyloxycarbonylpiperidin-3-yl)-ethylamino]-4-[5-N-(benzoyl)-aminobenzimidazol-1-yl]pyrimidine (30.5 mg, 0.053 mmol) was dissolved in CH2Cl2 (0.5 mL), and the mixture was cooled down to 0° C. To this was added 30percent HBr in acetic acid (0.2 mL) slowly and continued stirring at 0° C. for 5 min The bath was removed, and the reaction mixture was stirred at room temperature for 10 min then was diluted with H2O (2 mL). It was extracted with once CH2Cl2 (1 mL; discarded), then the aqueous layer was made neutral with saturated aqueous NaHCO3 and extracted with EtOAc (3*1 mL; discarded). The aqueous layer was made strongly basic (>pH 12) with SN NaOH, and was extracted with EtOAc (4*2 mL). The combined extracts were washed with brine and dried over Na2SO4. After removal of solvent under reduced pressure, 20.8 mg of free piperidine was obtained which was used without purification.

Hide Experimental Procedure

Schering Corporation

Patent: US6204265 B1, 2001 ; Title/Abstract Full Text Show Details

12.I.12.L:Preparation 12I-12L

Preparation 12I-12L Treat a solution (0.05-0.25 mmol) of the desired Boc protected piperidine obtained from Preparation 12E-12H, step 1, in CH2Cl2 with 1.5-5 eq mCPBA and stir for 2-18 h. Concentrate in vacuo and purify by silica gel 15 chromatography. Deprotect the Boc group using a procedure similar to that of Preparation 12A, step 3, to give the appropriate piperidine.

Hide Experimental Procedure

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6329385 B1, 2001 ; Title/Abstract Full Text Show Details

234:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine

Example 234 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and follow hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) δ: 1.65-1.93(2H,m), 1.94-2.28(4H,m), 2.34-2.70(4H,m), 2.81(1H,m), 2.96(2H,m), 3.78(3H,s), 5.28(2H,brs), 6.09(1H,t), 6.70-7.42(8H,m), 7.53-7.72(2H,m), 8.28(1H,brs), 8.49(1H,m). 3

Hide Experimental Procedure

Schering Corporation

Patent: US6204265 B1, 2001 ; Title/Abstract Full Text Show Details

6.O.1:EXAMPLE 6O

Step 1: Dissolve the product of Preparation 3, step 3 (2.0 g, 7.5 mmol) in CH3OH (50 mL) and treat with Pd(OH)2 (20percent on C, 50percent H2O) followed by H2 (40 psi). After shaking for 17 h on Parr shaker, filter through celite and concentrate to obtain the desired piperidine (1.33 g, 7.3 mmol, 98percent).

Hoechst Marion Roussel

Hide Experimental Procedure

Patent: US6239121 B1, 2001 ; Title/Abstract Full Text Show Details

Stare E:

Condensation of the Piperidine Stages C, D and E are carried out in a similar manner to Stages C, D and E of Example 1. 0.657 g of expected pure product is obtained (Rf AcOEt/TEA 92/8=0.21). NMR (CDCl3): 0.48 (s): CH3 in position 18; 2.47 (m): cyclic CH2-N; 2.70 (t): CH2 -N chain; 3.89 (tl): H11; 3.99 (t): CH2-O chain; 4.56: CH2-O ring; 5.78: OH; 5.87: H'3, H'4; 6.60-6.80: H1 and H2; 6.60-6.86: Ph-O.

Hide Experimental Procedure

AstraZeneca AB

Patent: US7235559 B1, 2007 ; Title/Abstract Full Text Show Details

332:Preparation of Compound 332 in Table 14

EXAMPLE 332 Preparation of Compound 332 in Table 14 An analogous reaction to that described in example 329, but starting with piperidine (85 mg, 1.0 mmol) yielded the title compound (57 mg, 53percent yield) as a white solid: 1H-NMR (DMSO-d ): 9.48 (s, 1H), 8.43 (d, 1H), 8.37 (s, 1H), 8.06 (dd, 1H), 7.78 (s, 1H), 7.51 (s, 1H), 7.40 (m, 3H), 7.15 (s, 1H), 6.96 (d, 1H), 5.37 (s, 2H), 4.15 (t, 2H), 3.94 (s, 3H), 2.39 (t, 2H), 2.32 (t, 4H), 1.92 (m, 2H), 1.48 (m, 4H), 1.37 (m, 2H): 6 MS (+ve ESI): 551.3 (M+H)+.

Hide Experimental Procedure

Freskos, John N.; Fobian, Y vette M.; Awasthi, Alok K.; Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Boehm, Terri L.; Carroll, Jeffery N.; Chandrakumar, Nizal S.; DeCrescenzo, Gary A.; Desai, Bipin N.; Heron, Marcia I.; Hockerman, Susan L.; Jull, Sara M.; Kassab, Darren J.; Kolodziej, Steve A.; McDonald, Joseph; Mischke, Deborah A.; Mullins, Patrick B.; Norton, Monica B.; Rico, Joseph G.; Talley, John J.; Trivedi, Mahima; Villamil, Clara I.; Wang, Lijuan Jane

Patent: US2004/24024 A1, 2004 ; Title/Abstract Full Text Show Details

53.E:Part E. Preparation of:

Part E. Preparation of: A mixture of the sulfone of Part D (10.0 g, 13.4 mmol) and 10percent palladium on carbon (1.43 g, 1.34 mmol) in methanol (50 mL) was placed under an H2 atmosphere with a balloon at ambient temperature for 20 hr. The mixture was filtered through a bed of celite and concentrated in vacuo to provide the piperidine in the form of a pale yellow oil (7.57 g, 92percent). The proton NMR spectrum was consistent for the desired compound.

Hide Experimental Procedure

Boehringer Ingelheim Pharmaceuticals, Inc.; Boehringer Ingelheim Pharma GmbH and Co. KG

Patent: US2004/33222 A1, 2004 ; Title/Abstract Full Text Show Details

each R4, R5, R6, R7, R9, R10, R11 and R12 is independently selected from the group consisting of: morpholine, piperidine, piperazine, imidazole and

Hide Experimental Procedure

Aventis Pharma S.A.

Patent: US2005/20572 A1, 2005 ; Title/Abstract Full Text Show Details

19.a:6-(phenylmethoxy)-1,6-diazabicyclo[3.2.1]octan-7-one

35.5 g of a colourless oily liquid is recovered which is purified by chromatography on silica, eluding with a dichloromethane/ethyl acetate mixture 95/5, then with a dichloromethane/ethyl acetate mixture 80/20. In this way 17.89 of 1,1-dimethylethyl 3-[(phenylmethoxy)amino]-1-piperidinecarboxylate of molecular formula C17H26N2O3 (M=306.41 g), is recovered in the form of a colourless oil. The corresponding yield is 72percent. 6.72 g (21.9 mmoles) of the piperidine obtained previously is dissolved in 22 ml of ethyl acetate cooled down to -10° C. 28 ml of a 4.0 mol/l solution of anhydrous hydrochloric acid in ethyl acetate is added dropwise, over 30 minutes. After 1 hour at 0° C., 40 ml of ethyl ether is added, the dihydrochloride precipitate is filtered and washed with ethyl ether. In this way 3.87 g of a white solid is obtained. By crystallizing the filtrate, 1.80 g of the desired product is also obtained. The product obtained is taken up in 60 ml of 1 N soda and 120 ml of ethyl acetate. After decanting, the aqueous phase is saturated with sodium chloride, then extracted twice with ethyl acetate. The organic phases are combined and dried over magnesium sulphate then concentrated to dryness under reduced pressure. In this way 3.67 g of N-(phenylmethoxy)-3-piperidinamine, of molecular formula C12H18N2O (M=206.29 g) is obtained, which corresponds to a yield of 81percent. 518 mg (2.5 mmoles) of the compound obtained previously is dissolved in 5 ml of anhydrous dichloromethane, then 0.5 ml of TEA is added. The whitish suspension obtained is cooled down to -65° C., then 12.5 ml of a 0.10 mol/l solution of diphosgene in dichloromethane is added over 15 minutes. After reaction for 45 minutes, the colourless solution is diluted with 15 ml of dichloromethane and treated with 15 ml of water. The medium is left to settle, then the aqueous phase is extracted with 20 ml of dichloromethane. The combined organic phases are dried over magnesium sulphate, then concentrated to dryness under reduced pressure.

Hide Experimental Procedure

Luly, Jay R.; Nakasato, Yoshisuke; Ohshima, Etsuo; Harriman, Geraldine C.B.; Carson, Kenneth G.; Ghosh, Shomir; Elder, Amy M.; Mattia, Karen M.

Patent: US2005/70549 A1, 2005 ;

Title/Abstract Full Text Show Details

234:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine

Example 234 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and follow hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) d: 1.65-1.93(2H,m), 1.94-2.28(4H,m), 2.34-2.70(4H,m), 2.81(1H,m), 2.96(2H,m), 3.78(3H,s), 5.28(2H,brs), 6.09(1H,t), 6.70-7.42(8H,m), 7.53-7.72(2H,m), 8.28(1H,brs), 8.49(1H,m). 3

Hide Experimental Procedure

Davies, David Thomas; Markwell, Roger Edward; Pearson, Neil David

Patent: US2004/53928 A1, 2004 ; Title/Abstract Full Text Show Details

51.b:cis-3-(R/S)-Aminocarbonyl-4-(S/R)-[trans-1-(2-furyl)-3-propenyl]amino-1-[2-(R)hydroxy-2-(6-methoxyquinolin-4-yl)]ethylpiperidine dioxalate

(b) cis-3-(R/S)-Ethoxycarbonyl-4-(S/R)-[trans-1-(2-furyl)-3-propenyl]amino piperidine. The 1-tert-butoxycarbonylpiperidine (51a) (1.06 g) was treated with trifluoroacetic acid (5 ml) and 1,3-dimethoxybenzene (3.12 ml) in dichloromethane (1). After 1.5 hours at room temperature, the mixture was evaporated and the residue was triturated with ether, dissolved in aqueous sodium bicarbonate and extracted with dichloromethane. The extracts were dried and evaporated, and the crude product was chromatographed on silica gel (methanol-dichloromethane) to give the piperidine (0.34 g). MS (+ve ion electrospray) m/z 279 (MH+).

Hide Experimental Procedure

Boerhinger Ingelheim Pharmaceuticals, Inc.

Patent: US6319921 B1, 2001 ; Title/Abstract Full Text Show Details

Boehringer Ingelheim Pharmaceuticals, Inc.

Patent: US2003/109703 A1, 2003 ; Title/Abstract Full Text Show Details

Boehringer Ingelheim Pharmaceuticals, Inc.

Patent: US2003/130309 A1, 2003 ; Title/Abstract Full Text Show Details

Boehringer Ingelheim Pharmaceuticals, Inc.

Patent: US6525046 B1, 2003 ; Title/Abstract Full Text Show Details

Boehringer Ingelheim Pharma GmbH and Co. KG

Patent: US2003/220336 A1, 2003 ; Title/Abstract Full Text Show Details

Boehringer Ingelheim Pharma GmbH and Co. KG

Patent: US2004/44020 A1, 2004 ; Title/Abstract Full Text Show Details

each R4, R5, R6, R7, R9, R10, R11 and R12 is independently selected from the group consisting of: morpholine, piperidine, piperazine, imidazole and

Hide Experimental Procedure

McDonald, Joseph J.; Kassab, Darren J.; Massa, Mark A.; Grapperhaus, Margaret L.; Schmidt, Michelle A.; Rico, Joseph G.; Mullins, Patrick B.; Brown, David L.

Patent: US2005/209278 A1, 2005 ; Title/Abstract Full Text Show Details

15.C:Preparation of N-hydroxy-1-(2-methoxyethyl)-4-{[4-(4-pentylpheyl)piperidin-1-yl]sulfonyl}piperidine-4-carboxamide Hydrochloride

Part C. Preparation of Piperidine Intermediate. To a solution of the alkene of Part B (2.93 g, 9.17 mmol) in methanol (20 mL) was added ammonium formate (1.74 g, 27.51 mmol) and 10percent Pd/C (0.917 g). The resulting mixture was heated at reflux. After 7 hr, the reaction mixture was cooled to ambient temperature and filtered through a pad of Celite.(R)., washing with methanol. The filtrate was concentrated in vacuo to produce a piperidine in the form of a yellow oil (2.10 g, quantitative yield).

Hide Experimental Procedure

McDonald, Joseph J.; Kassab, Darren J.; Massa, Mark A.; Grapperhaus, Margaret L.; Schmidt, Michelle A.; Rico, Joseph G.; Mullins, Patrick B.; Brown, David L.

Patent: US2005/209278 A1, 2005 ; Title/Abstract Full Text Show Details

16.C:Preparation of 4-{[4-(4-butoxyphenyl)piperidin-1-yl]sulfonyl}-N-hydroxy-1-(2-methoxyethyl)piperidine-4-carboxamide Hydrochloride

Part C. Preparation of Piperidine Intermediate. To a solution of the alkene of Part B (12.40 g, 38.57 mmol) in methanol (80 mL) was added ammonium formate (7.30 g, 115.71 mmol) and 10percent Pd/C (3.86 g). The resulting mixture was heated at reflux. After 3 hr, the reaction mixture was cooled to ambient temperature and filtered through a pad of Celite.(R)., washing with methanol. The filtrate was concentrated in vacuo to produce a piperidine in the form of a yellow oil (9.30 g, quantitative yield).

Hide Experimental Procedure

Fujimoto, Roger Aki; Krastel, Philipp; LaMarche, Matthew J.

Patent: US2009/186830 A1, 2009 ; Title/Abstract Full Text Show Details

15:Preparation of Piperidine (16)

Example 15 Preparation of Piperidine (16) Compound 16 is prepared as described in example 14. LC/MS: [M+H]+ 1179, Rt=0.74 min (method 1).

Hide Experimental Procedure

Fujimoto, Roger Aki; Krastel, Philipp; LaMarche, Matthew J.

Patent: US2009/186830 A1, 2009 ; Title/Abstract Full Text Show Details

55:Preparation of Piperidine (61)

Example 55 Preparation of Piperidine (61) Compound 61 is prepared according to the procedures described in example 34. LC/MS: [M+H]+ 1311, Rt=0.90 (method 1).

Hide Experimental Procedure

EPFL Ecole Polytechnique Federale de Lausanne

Patent: EP2111858 A1, 2009 ; Title/Abstract Full Text Show Details

Non-limiting examples of 1-aminocyclohexane derivatives used according to the invention include the 1-aminoalkylcyclohexane derivatives selected from the group consisting of: ... N-[(1S,SS)cis-5-ethyl-1,3,3-trimethylcyclohexyl]pyrrolidine or piperidine, N-(1,3,3-trimethyl-trans-5-ethylcyclohexyl)pyrrolidine or piperidine, N-[(1R,SS)trans-5-ethy1,3,3-trimethylcyclohexyl]pyrrolidine or piperidine, N-(1-ethyl-3,3,5,5-tetramethylyclohexyl)pyrrolidine or piperidine, N-(1-propyl-3,3,5,5-tetramethylcyclohexyl)pyrrolidine or piperidine, N-(1,3,3,5,5-pentamethylcyclohexyl)pyrrolidine,

Hide Experimental Procedure

FOREST LABORATORIES HOLDINGS LIMITED

Patent: US2009/275597 A1, 2009 ; Title/Abstract Full Text Show Details

Non-limiting examples of 1-aminocyclohexane derivatives used of the invention include: ... N-[(1S,SS)cis-5-ethyl-1,3,3-trimethylcyclohexyl]pyrrolidine or piperidine, N-(1,3,3-trimethyl-trans-5-ethylcyclohexyl)pyrrolidine or piperidine, N-[(1R,SS)trans-5-ethyl,3,3-trimethylcyclohexyl]pyrrolidine or piperidine, N-(1-ethyl-3,3,5,5-tetramethylyclohexyl)pyrrolidine or piperidine, N-(1-propyl-3,3,5,5-tetramethylcyclohexyl)pyrrolidine or piperidine, N-(1,3,3,5,5-pentamethylcyclohexyl)pyrrolidine,

Lippard, Stephen J.; Ziegler, Christopher J.

Patent: US6806289 B1, 2004 ; Location in patent: Page/Page column 107 ; Title/Abstract Full Text Show Details

Hide Experimental Procedure

Trifluoroacetic acid (TFA) 1-Hydroxybenzotriazole (HOBt)

Takeda Pharmaceutical Company Limited

Patent: US2010/112089 A1, 2010 ; Title/Abstract Full Text Show Details

Diisopropylether (DIPE) Piperidine

JSR Corporation

Patent: US2010/152308 A1, 2010 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

Examples of the nitrogen-containing heterocyclic compound having active hydrogen include the following compounds: ... pyrrolidine, pyrroline, pyrazolidine, pyrazoline, piperidine, piperazine, indole, isoindole, ...

Applied Genomics, Inc.; UAB Research Foundation

Patent: US2007/65888 A1, 2007 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

Applied Genomics, Inc.

Patent: US2011/15259 A1, 2011 ; Title/Abstract Full Text Show Details

Peptide (Synthesised by Research Genetics. Details given below) Piperidine (Cat. No. 80640, Fluka, available through Sigma) Sodium Bicarbonate (Cat. No. BP328-1, Fisher) Sodium Borate (Cat. No. B9876, Sigma) Sodium Carbonate (Cat. No. BP357-1, Fisher) Sodium Chloride (Cat. No. BP 358-10, Fisher) Sodium Hydroxide (Cat. No. SS 255-1, Fisher)

Ponomarev; D.ukareva; Sb.

Get. Kataliz v reak.ijach pol... i. prevr. geterocikl. soedin.Chem.Abstr., 1970 , p. 255 - 259 Get. Kataliz v reak.ijach pol... i. prevr. geterocikl. soedin.Chem.Abstr., vol. 78, # 4101s Full Text Show Details

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.

Patent: US2015/225399 A1, 2015 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

145.1:Steps 1-4:

Steps 1-4: Synthesis of ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1-[2-oxo-2-(1-piperidinyl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxylate This compound was prepared from N-{2-[(ethyloxy)carbonyl]-5-[(4-fluorophenyl)methyl]-3-pyridinyl}glycine and piperidine employing methods similar to those described in Example 11, Steps 2-4 and was obtained as a white solid: AP-MS: 466 (M-1, 100). A

Synthesize Find similar

Synthesize Find similar Rx-ID: 33880188

Find similar reactions

With ammonia; chlorocarbonylhydrido[4,5bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II) in toluene

T=180°C; P=33078.3 Torr; 12 h; AutoclaveInert atmosphere; Hide Experimental Procedure

BASF SE

Patent: US2012/232293 A1, 2012 ; Location in patent: Page/Page column 12; 16 ; Title/Abstract Full Text Show Details

Catalyst complex XIVb (for preparation, see below, weighed out under an inert atmosphere), solvent (such an amount that the total solvent volume is 50 ml) and the alcohol to be reacted were placed under an argon atmosphere in a 160 ml Parr autoclave (stainless steel V4A) having a magnetically coupled inclined blade stirrer (stirring speed: 200-500 revolutions/minute). The indicated amount of ammonia was introduced at room temperature either in precondensed form or directly from the pressurized NH3 gas bottle. If hydrogen was used, this was effected by iterative differential pressure metering. The steel autoclave was electrically heated to the temperature indicated and heated for the time indicated while stirring (500 revolutions/minute) (internal temperature measurement). After cooling to room temperature, venting the autoclave and outgassing the ammonia at atmospheric pressure, the reaction mixture was analyzed by GC (30m RTX5 amine 0.32 mm 1.5 μm). Purification of the particular products can, for example, be carried out by distillation. The results for the amination of 1,4-butanediol (table 1a, 1b), diethylene glycol (table 2) and monoethylene glycol (table 3), 2,5-furandimethanol (table 4), alkyldiols (table 5), 1,4-bis(hydroxymethyl)-cyclohexane (table 6) and aminoalcohols (table 7) are given below.

With chlorocarbonylhydrido[4,5bis(dicyclohexylphosphinomethyl)acridine]ruthenium(II); ammonia in toluene

T=180°C; P=33078.3 Torr; 12 h; AutoclaveInert atmosphere; Hide Experimental Procedure

BASF SE; SCHAUB, THOMAS; BUSCHHAUS, BORIS; BRINKS, MARION KRISTINA; SCHELWIES, MATHIAS; PACIELLO, ROCCO; MELDER, JOHANN-PETER; MERGER, MARTIN

Patent: JP5808437 B2, 2015 ; Location in patent: Paragraph 0099; 0113 ; Title/Abstract Full Text Show Details

General procedure: Example General Rules on the catalyst amination of alcohol with ammoniaaccording to the present invention (See below for manufacturing, initialweighed under an inert atmosphere) catalyst complex XIVb and, with the solvent(amount of up to solvent total amount reaches the 50ml), and the alcohol thatthe reaction is, under an argon atmosphere, magnetic coupling type tilt wingsParr autoclave of 160ml equipped with a stirrer (made of special steel V4A)(stirring speed: 200 to 500 rev / min) were charged in. At described the amountof ammonia at room temperature, it has been directly metered from thepreliminary condensed with or NH 3 gas cylinder. If hydrogen is used, this wasdone by repeated differential-pressure volume. Steel autoclave is electricheating heated to the temperature indicated, for a period of time described, ithas been heated under stirring (500 rev / min) (internal temperaturemeasurement). The autoclave was cooled to room temperature, depressurized,after performing outgassing of ammonia at atmospheric pressure, the reactionmixture was analyzed by GC (30m RTX5 Amin 0.32mm, 1.5μm). The desired product,for example, can be isolated by distillation A

Synthesize Find similar

Synthesize Find similar Rx-ID: 39503926 Find similar reactions

John, Jeremy M.; Loorthuraja, Rasu; Antoniuk, Evan; Bergens, Steven H.

Catalysis Science and Technology, 2015 , vol. 5, # 2 p. 1181 - 1186 Title/Abstract Full Text View citing articles Show Details

With [Ru(η3-C3H5)(Ph2P(CH2)2NH2)2]BF4; potassium tertbutylate; hydrogen in tetrahydrofuran

T=100°C; P=38002.6 Torr; 24 h; A

Synthesize Find similar

Synthesize Find similar Rx-ID: 39503927 Find similar reactions

John, Jeremy M.; Loorthuraja, Rasu; Antoniuk, Evan; Bergens, Steven H.

Catalysis Science and Technology, 2015 , vol. 5, # 2 p. 1181 - 1186 Title/Abstract Full Text View citing articles Show Details

With [Ru(η3-C3H5)(Ph2P(CH2)2NH2)2]BF4; potassium tertbutylate; hydrogen in tetrahydrofuran

T=100°C; P=38002.6 Torr; 24 h; Reagent/catalystTime; A

Synthesize Find similar

Synthesize Find similar Rx-ID: 30163062 Find similar reactions

A: 7% B: 93%

With RuCl2[PPh2(CH2)4PPh2][2-(H2NCH2)C5H4N]; potassium hydroxide in toluene

16 h; Inert atmosphereReflux;

Nova, Ainara; Balcells, David; Schley, Nathan D.; Dobereiner, Graham E.; Crabtree, Robert H.; Eisenstein, Odile

Organometallics, 2010 , vol. 29, # 23 p. 6548 - 6558 Title/Abstract Full Text View citing articles Show Details

With tri-ruthenium(0)dodecacarbonyl; N-phenyl-2(dicyclohexylphosphino)pyrrol in cyclohexane

T=140°C; 21 h; Inert atmosphereSchlenk techniqueAutoclave; Reagent/catalyst;

Pingen, Dennis; Vogt, Dieter

Catalysis Science and Technology, 2014 , vol. 4, # 1 p. 47 - 52 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 37361126 Find similar reactions

A: 63 %Spectr. B: 30 %Spectr.

With (4,5-bis-(di-isopropylphosphinomethyl)acridine)RuH(CO)Cl; ammonia; sodium hydroxide in 1,4-dioxane; water

T=135 - 150°C; P=4560.31 Torr; 110 h; Inert atmosphereSchlenk technique; TemperatureReagent/catalyst; A

Khusnutdinova, Julia R.; Ben-David, Yehoshoa; Milstein, David

Journal of the American Chemical Society, 2014 , vol. 136, # 8 p. 2998 - 3001 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

With [Ru(Ph2PCH2CH2NH2)2(η3-C3H5)]BF4; hydrogen; potassium hexamethylsilazane in tetrahydrofuran

T=100°C; P=38002.6 Torr; 24 h; Catalytic behavior; Overall yield = 82 percentSpectr.; Hide Experimental Procedure

Rx-ID: 38405931 Find similar reactions

THE GOVERNORS OF THE UNIVERSITY OF ALBERTA; Bergens, Steven; John, Jeremy M.

Patent: US2014/163225 A1, 2014 ; Location in patent: Paragraph 0262; 0263 ; Title/Abstract Full Text Show Details

6:Hydrogenation of Acyclic Amides

General procedure: An investigation was carried out with an acyclic amides using (5) and KN[Si(CH3)3]2. The reactions were performed using in situ prepared catalyst (5). The reaction conditions were as follows: P(H2)=50 atm, 100° C., 5/KN[Si(CH3)3]=1:40, [Substrate]=0.626 M in THF. Yield was determined by 1H NMR. For entry 1, the yield comprised 72percent Benzyl Alcohol and 14percent Benzyl Benzoate. For substrate (8i), anthracene was used as an internal standard. The results of these experiments are shown in FIGS. 1120 and in Table 3.] Substrate R R1 R2 Yield (percent) Turnover 8a Ph Ph Ph 100 1000 8b Ph Ph Me 96 960 8c Ph Me Me 50 500 8d Ph —(CH2)5— — 82 820 8e Ph Ph H 50 500 8f Ph Me H 27 270 8g Me Ph Ph 100 1000 8h Me Ph Me 100 1000 8i Me Me Me 50 500 8j Me Ph H

70 700

Synthesize Find similar

Synthesize Find similar Rx-ID: 38526735 Find similar reactions

A: 9% B: 15%

With [RuCl2(Ph2PCH2CH2NH2)2]; potassium tertbutylate; hydrogen; zinc(II) trifluoroacetate in 1,4-dioxane

T=100°C; P=22502.3 Torr; 18 h; Inert atmosphereAutoclave;

Kita, Yusuke; Higuchi, Takafumi; Mashima, Kazushi

Chemical Communications, 2014 , vol. 50, # 76 p. 11211 - 11213 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910954 Find similar reactions

Multi-step reaction with 2 steps 1.1: sulfuric acid / water / 20 - 30 °C 1.2: 120 °C / 36228.6 Torr / |Autoclave; |Sealed tube 2.1: 5 active carbon-supported ruthenium / water / 7 h / 150 °C / 67506.8 Torr / pH 3.1 View Scheme

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910955 Find similar reactions

Multi-step reaction with 2 steps 1.1: sulfuric acid / water / 20 - 30 °C 1.2: 120 °C / 36228.6 Torr / |Autoclave; |Sealed tube 2.1: 5 active carbon-supported ruthenium / water / 7 h / 180 °C / 52505.3 Torr / pH 3.1 View Scheme

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910956 Find similar reactions

Multi-step reaction with 3 steps 1.1: sulfuric acid / water / 20 - 30 °C 1.2: 120 °C / 36228.6 Torr / |Autoclave; |Sealed tube 2.1: 5 active carbon-supported ruthenium / water / 7 h / 150 °C / 67506.8 Torr / pH 3.1 3.1: hydrogen / 180 °C / 51755.2 Torr View Scheme

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar Rx-ID: 38910958 Find similar reactions

Synthesize Find similar

With 5 active carbon-supported ruthenium in water

T=150°C; P=67506.8 Torr; pH=3.1; 7 h;

Synthesize Find similar

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910959 Find similar reactions

With 5 active carbon-supported ruthenium in water

T=180°C; P=52505.3 Torr; pH=3.1; 7 h;

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910960 Find similar reactions

Multi-step reaction with 2 steps 1: 5 active carbon-supported ruthenium / water / 7 h / 150 °C / 67506.8 Torr / pH 3.1 2: hydrogen / 180 °C / 51755.2 Torr View Scheme

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910963 Find similar reactions

With hydrogen

T=180°C; P=51755.2 Torr;

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910968 Find similar reactions

Stage #1: With sulfuric acid in water

T=20 - 30°C; Stage #2: With hydrogen in water

T=180°C; P=51680.2 Torr; 24 h; AutoclaveSealed tube;

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 38910969 Find similar reactions

Stage #1: With sulfuric acid in water

Metkar, Pranit S.; Scialdone, Mark A.; Moloy, Kenneth G.

T=20 - 30°C; Stage #2: With hydrogen in water

T=150°C; P=51680.2 Torr; 24 h; AutoclaveSealed tube;

Green Chemistry, 2014 , vol. 16, # 10 p. 4575 - 4586 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 34834283 Find similar reactions

Jimenez, M. Victoria; Bartolome, M. Isabel; Perez-Torrente, Jesus J.; Gomez, Daniel; Modrego, F. Javier; Oro, Luis A.

ChemCatChem, 2013 , vol. 5, # 1 p. 263 - 276 Title/Abstract Full Text View citing articles Show Details

in THF-d8 (tetrahydrofuran-d8)

T=-100.16°C; Equilibrium constant;

Synthesize Find similar

Rx-ID: 35094888 Find similar reactions

A: 31 %Chromat. B: 18 %Spectr.

Difranco, Stephen A.; Staples, Richard J.; Odom, Aaron L.

Dalton Transactions, 2013 , vol. 42, # 7 p. 2530 - 2539 Title/Abstract Full Text View citing articles Show Details

in toluene

Kinetics; Time;

Synthesize Find similar

Synthesize Find similar Rx-ID: 36013286 Find similar reactions

With potassium phosphate; dichloro(cycloocta-1,5diene)palladium(II) in 1,4-dioxane

T=110°C; 10 h; Inert atmosphereSchlenk technique;

Li, Gaocan; Qian, Shengyou; Wang, Chunxia; You, Jingsong

Angewandte Chemie - International Edition, 2013 , vol. 52, # 30 p. 7837 - 7840 Angew. Chem., 2013 , vol. 125, # 30 p. 7991 - 7994,4 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 36013287 Find similar reactions

With potassium phosphate; N-methyl-2indolinone; dichloro(cycloocta-1,5-diene)palladium(II) in 1,4-dioxane

Li, Gaocan; Qian, Shengyou; Wang, Chunxia; You, Jingsong

Angewandte Chemie - International Edition, 2013 , vol. 52, # 30 p. 7837 - 7840 Angew. Chem., 2013 , vol. 125, # 30 p. 7991 - 7994,4 Title/Abstract Full Text View citing articles Show Details

T=110°C; 10 h; Inert atmosphereSchlenk technique; A

Synthesize Find similar

Synthesize Find similar Rx-ID: 33174700 Find similar reactions

in dichloromethane

T=25°C;

Saffari; Khorasani-Motlagh; Noroozifar

Russian Journal of Inorganic Chemistry, 2012 , vol. 57, # 1 p. 128 - 132 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 1630525 Find similar reactions

77%

With chlorosulphonyl isocyanate in diethyl ether

10 h; Ambient temperature;

Dhar, Durga N.; Bag, Amal K.

Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1983 , vol. 22, # 6 p. 600 Title/Abstract Full Text Show Details

With perchloric acid; ammonium sulphamate; sodium isothiocyanate

Singer, Sandra S.; Singer, George M.; Cole, Barbara B.

Journal of Organic Chemistry, 1980 , vol. 45, # 24 p. 4931 - 4935 Title/Abstract Full Text View citing articles Show Details

T=50°C; Rate constant;

Multi-step reaction with 2 steps 1: titanium(III) chloride; water / ethanol / 1 h / 20 °C / Inert atmosphere 2: titanium(III) chloride; water / tetrahydrofuran / pH 10 / Reflux; Alkaline aq. solution; Inert atmosphere View Scheme

Zhang, Yan; Tang, Qiang; Luo, Meiming

Organic and Biomolecular Chemistry, 2011 , vol. 9, # 13 p. 4977 - 4982 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 4420201 Find similar reactions

94%

With ammonia; hydrogen; Katalco 58

T=230°C; P=26252.1 Torr;

Shuikin, A. N.; Kliger, G. A.; Zaikin, V. G.; Glebov, L. S.

Russian Chemical Bulletin, 1995 , vol. 44, # 10 p. 1966 - 1968 Izvestiya Akademi Nauk, Seriya Khimicheskaya, 1995 , # 10 p. 2046 - 2048 Title/Abstract Full Text Show Details

With ammonia; hydrogen; γ-Al2O3 (45 weight percent), CuO (55 weight percent), hydrogenated T=220°C; P=15001.5 Torr; Product distribution / selectivity;

BASF AKTIENGESELLSCHAFT

Patent: WO2005/110969 A1, 2005 ; Location in patent: Page/Page column 23 ;

With ammonia; hydrogen; γ-Al2O3 (45 weight percent), CuO (45 weight percent), NiO (10 weight percent), hydrogenated T=210°C; P=15001.5 Torr; Product distribution / selectivity;

BASF AKTIENGESELLSCHAFT

Patent: WO2005/110969 A1, 2005 ; Location in patent: Page/Page column 26 ;

Title/Abstract Full Text Show Details

Hide Details

in water

Hide Experimental Procedure

Title/Abstract Full Text Show Details

2:Example 2

Example 2 The 1.7 ml of 1,5-pentandiol and water was fed onto the catalytic bed packed with Cu-ZSM-5 in the flow rate of 2 ml/h at 280° C. temperature. The yield of piperidine is 76.4 wt percent at conversion of 99.9 wt percent.

in water

Hide Experimental Procedure

COUNCIL OF SCIENTIFIC and INDUSTRIAL RESEARCH

Patent: US2002/183517 A1, 2002 ;

COUNCIL OF SCIENTIFIC and INDUSTRIAL RESEARCH

Patent: US2002/183517 A1, 2002 ; Title/Abstract Full Text Show Details

4:Example 4

Example 4 The 1.7 ml of 1,5-pentandiol and water was fed onto the catalytice bed packed with Ni-ZSM-5 in the flow rate of 2 ml/h at 280° C. temperature, The yield of piperidine is 90.2 wt percent at conversion of 99.9 wt percent.

COUNCIL OF SCIENTIFIC and INDUSTRIAL RESEARCH

Patent: US2002/183517 A1, 2002 ;

in water

Hide Experimental Procedure

Title/Abstract Full Text Show Details

5:Example 5

Example 5 The 1.7 ml of 1,5-pentandiol and water was fed onto the catalytice bed packed with Cu-ZSM-5 in the flow rate of 2 ml/h at 350° C. temperature. The yield of piperidine is 26.2 wt percent at conversion of 51.4 wt percent.

With ammonia; hydrogen; shaped bodies of reduced CuO/γ-Al2O3 (55 wtpercent/45 wtpercent) T=220 - 240°C; P=15001.5 Torr; Product distribution / selectivity; Hide Experimental Procedure

BASF SE

Patent: US2011/172430 A1, 2011 ; Location in patent: Page/Page column 9 ; Title/Abstract Full Text Show Details

Example 3; Shaped bodies having a size of 3.x.3 mm and 5.x.5 mm were examined in the reaction of pentanediol with ammonia to form piperidine at 220-240° C., a plant pressure of 20 bar and a WHSV of pentanediol of 0.31 kg/liter*h. An increase in selectivity to the reaction product by more than 10percent to about 92percent was observed when using the 3.x.3 mm shaped bodies compared to the 5.x.5 mm shaped bodies.

Synthesize Find similar

With ammonium cerium (IV) nitrate; water; acetic acid in dichloromethane

T=20°C; 4 h; Inert atmosphere; Hide Experimental Procedure

Synthesize Find similar

Rx-ID: 30064499 Find similar reactions

Pattanayak, Sankha; Sinha, Surajit

Tetrahedron Letters, 2011 , vol. 52, # 1 p. 34 - 37 Title/Abstract Full Text View citing articles Show Details

General procedure:

The substrate (1 equiv) was added to a solution of CAN (20 mol percent) in minimum amount of water (roughly 15 equiv). The reaction mixture was dissolved in dichloromethane and stirred magnetically. Acetic acid (10 equiv) was added to the solution and left to stir at rt for the required time mentioned in Table 2. Upon completion of the reaction, the solvent was evaporated under reduced pressure and worked up in the following methods. Method A: The solid residue was washed twice with petroleum ether to remove the by product trityl alcohol. The residue was then dissolved in methanol and filtered through a short pad of celite. Removal of the solvent under reduced pressure yielded the free amine. Method B: Water and acetic acid were removed from the reaction mixture in vacuo. The residue was dissolved in dry dichloromethane, followed by the addition of triethylamine (2.5 equiv) and acetic anhydride or benzoyl chloride (1.5 equiv). After the completion of the reaction, the solvent was evaporated. The residue was extracted with ethyl acetate twice. The combined organic layer was washed with water and brine and finally dried (Na2SO4). Solvent was removed under reduced pressure and the residue obtained was purified by silica gel column chromatography to afford the acylated amine.

Synthesize Find similar

With hydrazine hydrate in ethanol

Synthesize Find similar

Rx-ID: 30326515 Find similar reactions

Gupta, Archana; Sakhuja, Rajeev; Kushwaha, Khushbu; Jain, Subhash C.

2 h; Reflux;

Synthetic Communications, 2011 , vol. 41, # 3 p. 411 - 416 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Hide Experimental Procedure

Rx-ID: 30484810 Find similar reactions

University of Graz

Patent: EP2301627 A1, 2011 ; Title/Abstract Full Text Show Details

27:

(6RS,9RS)-(±)-N-Methyl-N-(4-oxo-6,9-diphenyl-3-azabicyclo[3.2.2]non-1-yl)-2-piperidino-acetamide (6RS,9RS)-(±)-2-Chloro-N-methyl-N-(4-oxo-6,9-diphenyl-3-azabicyclo[3.2.2]non-1-yl)acetamide (0.8 g, 2.1 mmol) gives with piperidine (6.3 g, 74 mmol) in the presence of a catalytic amount of KI a resin which is purified by column chromatography over aluminium oxide using CH2Cl2 : CH3OH = 34 :1 as eluent yielding a resin (426 mg, 46percent). 1H NMR (CDCl , δ, 400 MHz): 1.36 - 146 (m, 2H), 1.54 - 1.60 (m, 4H), 2.17 - 2.25 (m, 2H), 2.42 (s, 4H), 2.70 (dd, J = 11.7, 8.4 Hz, 1H), 2.87 (s, 1H), 3.08 (s, 3H), 3.10 - 3.11 (m, 2H), 3.23 (t, J = 12.8 Hz, 1H), 3.43 - 3.51 (m, 2H), 3.70 (d, J = 12.5 Hz, 1H), 3.88 (dd, J= 3

12.5, 4.0 Hz, 1H), 6.21 (d, J = 4.0 Hz, 1H), 7.17 - 7.39 (m, 10H) ppm.

Synthesize Find similar

75%

With titanium(III) chloride; water in tetrahydrofuran

pH=10; RefluxAlkaline aq. solutionInert atmosphere;

Synthesize Find similar

Rx-ID: 31160754 Find similar reactions

Zhang, Yan; Tang, Qiang; Luo, Meiming

Organic and Biomolecular Chemistry, 2011 , vol. 9, # 13 p. 4977 - 4982 Title/Abstract Full Text View citing articles Show Details

Synthesize

Rx-ID: 31548999

Find similar

T=405.6°C; P=114 Torr; Kinetics; PressureTemperature;

Find similar

Find similar reactions

Reyes, Andreina; Dominguez, Rosa M.; Tosta, Maria; Herize, Armando; Chuchani, Gabriel

Journal of Physical Organic Chemistry, 2011 , vol. 24, # 1 p. 74 - 82 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

in acetonitrile

0.166667 h; UV-irradiation; Reactivity; Hide Experimental Procedure

Synthesize Find similar

Rx-ID: 31633306 Find similar reactions

WAKO PURE CHEMICAL INDUSTRIES, LTD.

Patent: US2011/233048 A1, 2011 ; Location in patent: Page/Page column 21 ; Title/Abstract Full Text Show Details

13:

Example 13Measurement Test of Reactivity for Light (Active Energy Ray); 1 mg of the compound obtained by Example 1 to 4 was placed to quartz tube respectively, and was dissolved into 500 μL of acetonitrile. Subsequently, this solution was subjected to light (active energy rays) irradiation by 100 W high-pressure mercury lamp (HL-100 type; manufactured by Fuji-Glass Co.) for 10 minutes in 3 cm of measurement distance. Appropriate amounts of each solutions before and after irradiated with light (active energy rays) were spotted onto the TLC-plate (manufactured by Merck Co.), subsequently, ninhydrin spray (manufactured by Wako Pure Chemical Industries, Ltd.) was sprayed, and was heated by heat-gun for 30 seconds, and it was confirmed that whether ninhydrin reaction was occurred or not, that is, base (amine) can be released or not. Measurement results are shown in Table 2.

Synthesize Find similar

in acetonitrile

0.166667 h; UV-irradiation; Reactivity; Hide Experimental Procedure

Synthesize Find similar

Rx-ID: 31633308 Find similar reactions

WAKO PURE CHEMICAL INDUSTRIES, LTD.

Patent: US2011/233048 A1, 2011 ; Location in patent: Page/Page column 21 ; Title/Abstract Full Text Show Details

13:

Synthesize Find similar

Rx-ID: 31633310 Find similar reactions

WAKO PURE CHEMICAL INDUSTRIES, LTD.

Patent: US2011/233048 A1, 2011 ; Location in patent: Page/Page column 21 ;

in acetonitrile

0.166667 h; UV-irradiation; Reactivity; Hide Experimental Procedure

Title/Abstract Full Text Show Details

13:

Synthesize Find similar

Synthesize Find similar Rx-ID: 31940907 Find similar reactions

With cis-[Ru(CH3CN)2(η3-C3H5)(CO1,5cyclooctadiene)]BF4; hydrogen; potassium hexamethylsilazane; 2(diphenylphosphino)ethylamine in tetrahydrofuran

T=100°C; P=38002.6 Torr; 24 h; Autoclave;

John, Jeremy M.; Bergens, Steven H.

Angewandte Chemie - International Edition, 2011 , vol. 50, # 44 p. 10377 - 10380 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 32134639

Find similar reactions

A: 57 %Chromat. B: 63 %Chromat.

With [RuH(CO)(BPy-tPNN*)]; hydrogen in tetrahydrofuran

T=110°C; P=10336.7 Torr; 72 h; chemoselective reaction;

Balaraman, Ekambaram; Ben-David, Yehoshoa; Milstein, David

Angewandte Chemie - International Edition, 2011 , vol. 50, # 49 p. 11702 - 11705 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 32556430 Find similar reactions

A: 97 %Chromat. B: 96%

With 40 potassium fluoride/alumina

0.0666667 h; Microwave irradiationNeat (no solvent);

Zhang, Xiuli; Luo, Kai; Chen, Wei; Wang, Lei

Chinese Journal of Chemistry, 2011 , vol. 29, # 10 p. 2209 - 2212 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

92%

Synthesize Find similar

With cesium fluoride supported on Celite T=120°C; 2.5 h; chemoselective reaction;

Rx-ID: 33197770 Find similar reactions

Tamaddon, Fatemeh; Nasiri, Alireza; Farokhi, Somayeh

Catalysis Communications, 2011 , vol. 12, # 15 p. 1477 - 1482 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 1506389 Find similar reactions

A: 2 % Chromat. B: 6 % Chromat. C: 90 % Chromat.

With hydrogen; platinum on silica

T=150°C; other temperatures; further reactions with other heterocycles; Product distribution;

Guttieri, Mary J.; Maier, Wilhelm F.

Journal of Organic Chemistry, 1984 , vol. 49, # 16 p. 2875 - 2880 Title/Abstract Full Text View citing articles Show Details

With hydrogen in decaline

T=224.84°C; P=22502.3 Torr; Gas phase;

Valdevenito; Garcia; Escalona; Gil-Llambias; Rasmussen; Lopez-Agudo

Catalysis Communications, 2010 , vol. 11, # 14 p. 1154 - 1156 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 29458225 Find similar reactions

Beamson, Graham; Papworth, Adam J.; Philipps, Charles; Smith, Andrew M.; Whyman, Robin

Advanced Synthesis and Catalysis, 2010 , vol. 352, # 5 p. 869 - 883 Title/Abstract Full Text View citing articles Show Details

With tri-ruthenium(0)dodecacarbonyl; hydrogen; molybdenum hexacarbonate in ethylene glycol dimethyl ether

T=160°C; P=75007.5 Torr; 16 h; Inert atmosphere;

Synthesize Find similar

With palladium 10 on activated carbon; hydrogen; 1-n-butyl-3methylimidazolium tetrafluoroborate in methanol

T=20°C; P=760.051 Torr; 16 h;

Choi, Jin Kyu; Jeon, Byung Sun; Cho, Jong Hyun; Kim, B. Moon

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 3 p. 735 - 738 Title/Abstract Full Text View citing articles Show Details

Rx-ID: 29596017 Find similar reactions

Synthesize Find similar Rx-ID: 8624596 Find similar reactions

Synthesize Find similar

in acetonitrile

T=24.84°C; complex dissociation; Equilibrium constant;

Magonski, Jozef; Rajzer, Barbara

Journal of the Chemical Society. Perkin Transactions 2, 2000 , # 6 p. 1181 - 1185 Title/Abstract Full Text View citing articles Show Details

in 1,4-dioxane

T=24.84°C; Ionic liquid; Equilibrium constant;

D'Anna, Francesca; Vitale, Paola; Noto, Renato

Journal of Organic Chemistry, 2009 , vol. 74, # 16 p. 6224 - 6230 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 27964283 Find similar reactions

With Al2(NMe2)6 in toluene

T=90°C; 16 h; KineticsEquilibrium constant;

Hoerter, Justin M.; Otte, Karin M.; Gellman, Samuel H.; Cui, Qiang; Stahl, Shannon S.

Journal of the American Chemical Society, 2008 , vol. 130, # 2 p. 647 - 654 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 27964284 Find similar reactions

With Al2(NMe2)6 in toluene

T=90°C; 16 h; Equilibrium constant;

Synthesize Find similar

Hoerter, Justin M.; Otte, Karin M.; Gellman, Samuel H.; Cui, Qiang; Stahl, Shannon S.

Journal of the American Chemical Society, 2008 , vol. 130, # 2 p. 647 - 654 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 27964285 Find similar reactions

With Al2(NMe2)6 in toluene

T=90°C; 16 h; Equilibrium constant;

Synthesize Find similar

Hoerter, Justin M.; Otte, Karin M.; Gellman, Samuel H.; Cui, Qiang; Stahl, Shannon S.

Journal of the American Chemical Society, 2008 , vol. 130, # 2 p. 647 - 654 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 27964286 Find similar reactions

With Al2(NMe2)6 in toluene

T=90°C; 16 h; Equilibrium constant;

Hoerter, Justin M.; Otte, Karin M.; Gellman, Samuel H.; Cui, Qiang; Stahl, Shannon S.

Journal of the American Chemical Society, 2008 , vol. 130, # 2 p. 647 - 654 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

91%

Synthesize Find similar

With magnesium; acetic acid in methanol

T=20°C;

Rx-ID: 28225273 Find similar reactions

Tang, Guo; Ji, Tao; Hu, An-Fu; Zhao, Yu-Fen

Synlett, 2008 , # 12 p. 1907 - 1909 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar Rx-ID: 28326162 Find similar reactions

Synthesize Find similar

With water in ethanol

T=25°C; Acidic conditions; Kinetics;

Synthesize Find similar

Humeres, Eduardo; Byung, Sun Lee; Debacher, Nito Angelo

Journal of Organic Chemistry, 2008 , vol. 73, # 18 p. 7189 - 7196 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 28326169 Find similar reactions

With water in ethanol

T=25°C; Acidic conditions; Kinetics;

Humeres, Eduardo; Byung, Sun Lee; Debacher, Nito Angelo

Journal of Organic Chemistry, 2008 , vol. 73, # 18 p. 7189 - 7196 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 11226937 Find similar reactions

With oxonium in phosphate buffer; acetonitrile

T=25°C; pH=3.0; Kinetics;

Piggott, Andrew M.; Karuso, Peter

Tetrahedron Letters, 2007 , vol. 48, # 42 p. 7452 - 7455 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

A: 90.4%

Rx-ID: 25782795 Find similar reactions

Wakamoto Pharmaceutical Co., Ltd.

Patent: EP1820799 A1, 2007 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

71:Example 71

Example 71 (4S)-1-[4-(1H-indol-5-yl)-3-[3-(1-piperidinyl) propoxy]benzoyl]-4-methyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine was obtained by the same procedure as in Example 57 using the compound in Reference Example 191 and piperidine (yield: 90.4percent). A

Synthesize Find similar

Rx-ID: 27576738 Find similar reactions

With CH3SO3H in methanol; acetone

Kinetics; Au complex in acetone added to a methanolic soln. of Cl(1) at 25°C in the presence of 0.1 M/l CH3SO3H; not isolated, detected by UV;

Pitteri, Bruno; Bortoluzzi, Marco

European Journal of Inorganic Chemistry, 2007 , # 28 p. 4456 - 4461 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 11050402 Find similar reactions

Monsalve, Angiebelk; Rosas, Felix; Tosta, Maria; Herize, Armando; Dominguez, Rosa M.; Brusco, Doris; Chuchani, Gabriel

International Journal of Chemical Kinetics, 2006 , vol. 38, # 2 p. 106 - 114 Title/Abstract Full Text View citing articles Show Details

T=420.8°C; P=13 Torr; Kinetics; Further Variations:PressuresTemperatures;

Synthesize Find similar

Synthesize Find similar Rx-ID: 11050406 Find similar reactions

Monsalve, Angiebelk; Rosas, Felix; Tosta, Maria; Herize, Armando; Dominguez, Rosa M.; Brusco, Doris; Chuchani, Gabriel

International Journal of Chemical Kinetics, 2006 , vol. 38, # 2 p. 106 - 114 Title/Abstract Full Text View citing articles Show Details

T=391.8°C; P=53.5 Torr; Kinetics; Further Variations:PressuresTemperatures;

Synthesize Find similar

A: 32%

Hide Experimental Procedure

Rx-ID: 10556234 Find similar reactions

Sepracor, Inc.

Patent: US2005/80078 A1, 2005 ; Title/Abstract Full Text Show Details

3:Synthesis of [1-(4-chloro-phenyl)-cyclobutyl]-(3-phenoxymethyl piperidin-1yl)-methadone

EXAMPLE 3 Synthesis of [1-(4-chloro-phenyl)-cyclobutyl]-(3-phenoxymethyl piperidin-1yl)-methadone A solution of 1 (2.07 g, 6.72 mmoles), triphenylphosphine (2.64 g, 10.08 mmole), and phenol (1.27 g, 13.44 mmoles) dissolved in anhydrous ether (50 mL) was cooled in a brine bath to -5° C. DEAD (1.60 mL, 10.08 mmoles) dissolved in ether (10 mL) was added to the cooled stirring reaction mixture. After completion of addition, the reaction mixture continued stirring at -5° C. After 4h, the reaction mixture was concentrated and crude material was dissolved in a hexane/ethyl acetate mixture (70percent hexanes:30percent ethyl acetate, 30 mL). Phosphine by-products precipitated and were filtered off. The filtrate was concentrated to yield an oil. This oil was purified using silica gel chromatography (100percent hexanes-1:1 hexanes: EtOAc) to yield the amine 3 (840 mg, 2.19 mmole, 32percent). LRMS: M+384.

Synthesize Find similar

Rx-ID: 10729322 Find similar reactions

55%

Synthesize Find similar

With potassium carbonate in N,N-dimethyl-formamide

McDonald, Joseph J.; Kassab, Darren J.; Massa, Mark A.; Grapperhaus, Margaret L.; Schmidt, Michelle A.; Rico, Joseph G.; Mullins, Patrick B.; Brown, David L.

Patent: US2005/209278 A1, 2005 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

22.B:Preparation of 1-ethyl-4-{[4-(3-fluoro-4-pentylphenyl)piperazin-1-yl]sulfonyl}-N-hydroxypiperidine-4-carboxamine Hydrochloride

Part B. Preparation of: To a 75° C. mixture of 18-crown-6 (3.05 g, 11.6 mmol), potassium carbonate (32.0 g, 232 mmol), and 1,5-dichloro-3-ethyl-3-azapentane hydrochloride (9.58 g, 46.4 mmol) (synthetic procedure in J. Org. Chem. 1993, 58, 1359-1366) in DMF (197 mL) under N2 was added drop wise a solution of tert-butyl [(4-benzylpiperazin-1-yl)sulfonyl]acetate (13.7 g, 38.7 mmol) in DMF (73 mL). The resulting mixture was heated for 15 hr. The ambient reaction mixture was filtered, and the filtrate was concentrated in vacuo. Chromatography (silica gel; hexane/ethyl acetate) provided the piperidine as a yellow solid (9.66 g, 55percent yield): HR-MS MH+ calcd. for C23H38N3O4S 452.2583, found 452.2600. A

Synthesize Find similar

Synthesize Find similar Rx-ID: 23672087 Find similar reactions

With [Fluorescein]-Fluorescein in DMF (N,N-dimethyl-formamide)

Irradiation at 365 nm; Rate constant; Hide Experimental Procedure

Gao, Xiaolian

Patent: US6965040 B1, 2005 ; Location in patent: Page/Page column 18-19 ; Title/Abstract Full Text Show Details

Example V; Photometric Analysis of the Photoreaction of NPPOC-pip; This experiment demonstrates efficient generation of the base piperidine upon light irradiation of a PGB-P as monitored by increased UV absorbance value of the dye and pH indicator fluorescein as a function of light irradiation time.Fluorescein was purified in the lactone form as follows: the dye was dissolved in dilute aqueous NaOH, filtered, precipitated by adding dilute HCl, and dried under vacuum overnight. A stock solution of fluorescein (12 μM) in distilled DMF was prepared. To calibrate the absorption of fluorescein, different amounts of piperidine in DMF were added to 0.5 mL of the fluorescein solution in a 1 cm quartz cuvette. After mixing, the UV-Vis absorption spectra of the mixture were recorded. The increase of absorbance at 521 nm was correlated to the amount of piperidine added (after volume correction calculations). 2-(2-nitrophenyl)propoxycarbonyl piperidine (5.84 mg, 20 mM) in 1 mL DMF was prepared and irradiated at 365 nm using a collimated light source (20 mW, Oriel, Stanford, Calif.). Aliquots (10 to 20 μL) of the irradiated sample were added to fresh fluorescein solution (0.5 mL, 12 μM) and to DMF (0.5 mL). Absorbance at 521 nm was recorded (aliquots of the non-irradiated photogenerated base mixture in DMF was used to verify that absorbance of the photoproducts at 521 nm was negligible) and correlated to the amount of piperidine produced upon irradiation. Measurements for calibration and irradiated samples were carried out the same day and repeated three times.In FIG. 7 (curve 3), the estimated concentration of piperidine produced upon increasing irradiation time is plotted. The formation of piperidine under the conditions used follows a first order kinetics relationship and the apparent rate constant for formation of piperidine derived is 3.0.x.10-3+/-0.1 s-. A

Synthesize Find similar

Rx-ID: 24005598 Find similar reactions

Millennium Pharmaceuticals, Inc.

Patent: US2002/169155 A1, 2002 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

235:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine.

EXAMPLE 235 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) d: 2.35-2.77 (8H, m), 3.06-3.26 (2H, m), 3.78 (3H, s), 5.29 (2H, brs), 6.05-6.22 (2H, m), 6.70-6.88 (3H, m), 7.07-7.38 (5H, m), 7.60 (1H, dd), 7.87 (1H, m), 8.42 (1H, brs), 8.50 (1H, m). 3

LULY, JAY R.; NAKASATO, YOSHISUKE; OHSHIMA, ETSUO; SONE, HIROKI; KOTERA, OSAMU; HARRIMAN, GERALDINE C.B.

Patent: US2002/119973 A1, 2002 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

235:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine.

EXAMPLE 235 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) d: 2.35-2.77 (8H,m), 3.06-3.26 (2H,m) 3.78 (3H,s), 5.29 (2H,brs), 6.05-6.22 (2H,m), 6.70-6.88 (3H,m), 7.07-7.38 (5H,m), 7.60 (1H,dd), 7.87 (1H,m), 8.42 (1H,brs), 8.50 (1H,m). 3

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6509346 B2, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

235:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine.

EXAMPLE 235 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) δ: 2.35-2.77 (8H, m), 3.06-3.26 (2H, m), 3.78 (3H, s), 5.29 (2H, brs), 6.05-6.22 (2H, m), 6.70-6.88 (3H, m), 7.07-7.38 (5H, m), 7.60 (1H, dd), 7.87 (1H, m), 8.50 (1H, m). 3 Hide Details

Luly, Jay R.; Nakasato, Yoshisuke; Ohshima, Etsuo; Harriman, Geraldine C.B.; Carson, Kenneth G.; Ghosh, Shomir; Elder, Amy M.; Mattia, Karen M.

Patent: US2005/70549 A1, 2005 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

235:1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine

Example 235 1-[3-(5,11-Dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidine)propyl]-4-(indol-3-yl)-1,2,3,6-tetrahydropyridine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(indol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) d: 2.35-2.77(8H,m), 3.06-3.26(2H,m), 3.78(3H,s), 5.29(2H,brs), 6.05-6.22(2H,m), 6.70-6.88(3H,m), 7.07-7.38(5H,m), 7.60(1H,dd), 7.87(1H,m), 8.42(1H,brs), 8.50(1H,m). 3 A

Synthesize Find similar

Hide Experimental Procedure

Synthesize Find similar

Rx-ID: 24005599 Find similar reactions

Millennium Pharmaceuticals, Inc.

Patent: US2002/169155 A1, 2002 ; Title/Abstract Full Text Show Details

195:4-(7-Chloroindol-3-yl)-1-[3-(5, 11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine.

EXAMPLE 195 4-(7-Chloroindol-3-yl)-1-[3-(5, 11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) δ: 2.37-2.76 (8H, m), 3.14 (2H, m), 3.78 (3H, s), 5.29 (2H, brs), 6.02-6.23 (2H, m), 6.67-6.90 (3H, m), 7.05 (1H, dd), 7.12-7.33 (3H, m), 7.60 (1H, dd), 7.77 (1H, m), 8.50 (1H, dd), 9.06 (1H, br s). 3

Hide Experimental Procedure

LULY, JAY R.; NAKASATO, YOSHISUKE; OHSHIMA, ETSUO; SONE, HIROKI; KOTERA, OSAMU; HARRIMAN, GERALDINE C.B.

Patent: US2002/119973 A1, 2002 ; Title/Abstract Full Text Show Details

195:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine.

EXAMPLE 195 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) d: 2.37-2.76 (8H,m), 3.14 (2H,m), 3.78 (3H,s), 5.29 (2H,brs), 6.02-6.23 (2H,m), 6.67-6.90 (3H,m), 7.05 (1H,dd), 7.12-7.33 (3H,m), 7.60 (1H,dd), 7.77 (1H,m), 8.50 (1H,dd), 9.06 (1H,br s). 3

Hide Experimental Procedure

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6509346 B2, 2003 ; Title/Abstract Full Text Show Details

195:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine.

EXAMPLE 195 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) δ: 2.37-2.76 (8H, m), 3.14 (2H, m), 3.78 (3H, s), 5.29 (2H, brs), 6.02-6.23 (2H, m), 6.67-6.90 (3H, m), 7.05 (1H, dd), 7.12-7.33 (3H, m), 7.60 (1H, dd), 7.77 (1H, m), 8.50 (1H, dd), 9.06 (1H, brs). 3 Hide Details

Hide Experimental Procedure

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6329385 B1, 2001 ; Title/Abstract Full Text Show Details

195:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine.

Example 195 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine. The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) δ: 2.37-2.76(8H,m), 3.14(2H,m), 3.78(3H,s), 5.29(2H,brs), 6.02-6.23(2H,m), 6.67-6.90(3H,m), 7.05(1H,dd), 7.12-7.33(3H,m), 7.60(1H,dd), 7.77(1H,m), 8.50(1H,dd), 9.06(1H,br s). 3

Hide Experimental Procedure

Luly, Jay R.; Nakasato, Yoshisuke; Ohshima, Etsuo; Harriman, Geraldine C.B.; Carson, Kenneth G.; Ghosh, Shomir; Elder, Amy M.; Mattia, Karen M.

Patent: US2005/70549 A1, 2005 ; Title/Abstract Full Text Show Details

195:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine

Example 195 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-1,2,3,6-tetrahydropyridine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)-1,2,3,6-tetrahydropyridine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993). 1H-NMR (CDCl ) δ: 2.37-2.76(8H,m), 3.14(2H,m), 3.78(3H,s), 5.29(2H,brs), 6.02-6.23(2H,m), 6.67-6.90(3H,m), 7.05(1H,dd), 7.12-7.33(3H,m), 7.60(1H,dd), 7.77(1H,m), 8.50(1H,dd), 9.06(1H,br s). 3 A

Synthesize Find similar

Rx-ID: 24005600 Find similar reactions

LULY, JAY R.; NAKASATO, YOSHISUKE; OHSHIMA, ETSUO; SONE, HIROKI; KOTERA, OSAMU; HARRIMAN, GERALDINE C.B.

Patent: US2002/119973 A1, 2002 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

186:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine

EXAMPLE 186 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and following hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) d: 1.66-1.88 (2H,m), 1.92-2.22 (4H,m), 2.32-2.63 (4H,m), 2.78 (1H,m), 2.97 (2H,m), 3.79 (3H,s), 5.29 (2H,brs), 6.09 (1H,t), 6.70-6.87 (3H,m), 6.97-7.07 (2H,m), 7.12-7.30 (2H,m), 7.52 (1H,m), 7.59 (1H,dd), 8.45 (1H,brs), 8.50 (1H,dd). 3

Millennium Pharmaceuticals, Inc.

Patent: US2002/169155 A1, 2002 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6509346 B2, 2003 ; Title/Abstract Full Text Show Details

186:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine

EXAMPLE 186 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and following hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) δ: 1.66-1.88 (2H, m), 1.92-2.22 (4H, m), 2.32-2.63 (4H, m), 2.78 (1H, m), 2.97 (2H, m), 3.79 (3H, s), 5.29 (2H, brs), 6.09 (1H, t), 6.70-6.87 (3H, m), 6.97-7.07 (2H, m), 7.12-7.30 (2H, m), 7.52 (1H, m), 7.59 (1H, dd), 8.45 (1H, brs), 8.50 (1H, dd). 3

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6329385 B1, 2001 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

Luly, Jay R.; Nakasato, Yoshisuke; Ohshima, Etsuo; Harriman, Geraldine C.B.; Carson, Kenneth G.; Ghosh, Shomir; Elder, Amy M.; Mattia, Karen M.

Patent: US2005/70549 A1, 2005 ; Title/Abstract Full Text Show Details

186:4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine

Example 186 4-(7-Chloroindol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloroindol-3-yl)piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 36:4006-4014 (1993) and following hydrogenation described in Example 58, step 3. 1H-NMR(CDCl ) δ: 1.66-1.88(2H,m), 1.92-2.22(4H,m), 2.32-2.63(4H,m), 2.78(1H,m), 2.97(2H,m), 3.79(3H,s), 5.29(2H,brs), 6.09(1H,t), 6.70-6.87(3H,m), 6.97-7.07(2H,m), 7.12-7.30(2H,m), 7.52(1H,m), 7.59(1H,dd), 8.45(1H,brs), 8.50(1H,dd). 3 A

Synthesize Find similar

Rx-ID: 9581193 Find similar reactions

in tert-butyl alcohol

T=65 - 79°C; pH=11; Product distribution; Further Variations:SolventspH-valuesTemperatures;

Synthesize Find similar

Szabo, Anna; Galstnibos-Farago, Agnes; Mucsi, Zoltan; Timari, Geza; Vasvari-Debreczy, Lelle; Hermecz, Istvan

European Journal of Organic Chemistry, 2004 , # 4 p. 687 - 694 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Synthesize Find similar Rx-ID: 9610192 Find similar reactions

Arimitsu, Koji; Ichimura, Kunihiro

Journal of Materials Chemistry, 2004 , vol. 14, # 3 p. 336 - 343 Title/Abstract Full Text View citing articles Show Details

in 1,4-dioxane-d8

T=100°C; Product distribution; Further Variations:Solvents;

Synthesize Find similar

96%

Synthesize Find similar

With [BnEt3N]2MoS4 in acetonitrile

T=20°C; 2 h;

Rx-ID: 9746146 Find similar reactions

Bhat, Ramakrishna G.; Ghosh, Yagnaseni; Chandrasekaran, Srinivasan

Tetrahedron Letters, 2004 , vol. 45, # 43 p. 7983 - 7985 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 25782794 Find similar reactions

Shin-Etsu Chemical Co., Ltd.

Patent: US6743564 B2, 2004 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

S.40:Synthesis of 1-piperidinepropiononitrile (Amine 40)

Synthesis Example 40 Synthesis of 1-piperidinepropiononitrile (Amine 40) By following the same procedure as Synthesis Example 39 except that piperidine was used instead of pyrrolidine, 1-piperidinepropiononitrile was synthesised l(boiling point: 110° C./210 Pa).

Synthesize Find similar

Rx-ID: 25896574 Find similar reactions

Synthesize Find similar

Hale, Jeffrey J; Caldwell, Charles G.; Kim, Dooseop; Shen, Dong-Ming; Mills, Sander G.; Chapman, Kevin T.; Chen, Liya; MacCoss, Malcolm; Gentry, Amy; Lynch, Christopher L.; Willoughby, Christopher A.; Cheng, Yuan

Patent: US2004/87552 A1, 2004 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

66.71:EXAMPLES 66-71

EXAMPLES 66-71 Examples 66-71 were prepared using procedures analogous to those described in Examples 1 and 2 using Aldehyde 4, Pyrrolidine 2 and the appropriate piperidine, which were prepared using procedures analogous to that described for Piperidine 9.

Patent: US2004/87552 A1, 2004 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

87.92:EXAMPLES 87-92

EXAMPLES 87-92 Examples 87-92 were prepared using procedures analogous to those described in Examples 1 and 2 using Aldehyde 4, Pyrrolidine 2 and the appropriate piperidine, which were prepared using procedures analogous to that described for Piperidine 9.

Synthesize Find similar Rx-ID: 9465991 Find similar reactions

Synthesize Find similar

Lemek, Tadeusz; Mayr, Herbert

Journal of Organic Chemistry, 2003 , vol. 68, # 18 p. 6880 - 6886 Title/Abstract Full Text View citing articles Show Details

in water; dimethyl sulfoxide

T=20°C; Kinetics;

Synthesize Find similar

Synthesize Find similar Rx-ID: 9494028 Find similar reactions

Lemek, Tadeusz; Mayr, Herbert

Journal of Organic Chemistry, 2003 , vol. 68, # 18 p. 6880 - 6886 Title/Abstract Full Text View citing articles Show Details

in water; dimethyl sulfoxide

T=20°C; Kinetics;

Synthesize Find similar

Synthesize Find similar Rx-ID: 9494777 Find similar reactions

in water; dimethyl sulfoxide

T=20°C; Kinetics;

Lemek, Tadeusz; Mayr, Herbert

Journal of Organic Chemistry, 2003 , vol. 68, # 18 p. 6880 - 6886 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 23857898 Find similar reactions

Chen, Jian Jeffrey; Dunn, James Patrick; Goldstein, David Michael; Stahl, Christoph Martin

Patent: US2003/171584 A1, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

29.B:Step B

Step B Preparation of Benzyl Piperidin-4-ylcarbamate The benzyl amine (27.8 g, 85.7 mmol) was dissolved in 400 mL of methylene chloride at room temperature and 1-chloro-ethylchloroformate (25.4 g, 178 mmol) in 50 mL of methylene chloride was added dropwise via addition funnel. After addition was complete, the reaction mixture was stirred at room temperature for 3 hours. The solvent and volatiles were removed under reduced pressure and methanol 500 mL) was added. The reaction was heated to reflux with stirring for 1 hour and then cooled to room temperature. Removal of the reaction solution via evaporation yielded 26.3 g of the piperidine as an off-white solid (mass spec. M+1=235, MP=190.7-192.2° C.). A

Synthesize Find similar

Rx-ID: 23857899 Find similar reactions

Halazy, Serge; Quattropani, Anna; Bombrun, Agnes; Schwarz, Mattias; Thomas, Russel; Baxter, Anthony

Patent: US2003/171309 A1, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

Halazy, Serge; Quattropani, Anna; Scheer, Alexander; Schwarz, Mattias; Thomas, Russell; Baxter, Antony

Patent: US2003/212012 A1, 2003 ; Title/Abstract Full Text Show Details

216:(3EZ,5S)-1-[4-(dimethylamino)butanoyl]-5-(1-piperidinylcarbonyl)-3-pyrrolidinone O-methyloxime

Example 216 (3EZ,5S)-1-[4-(dimethylamino)butanoyl]-5-(1-piperidinylcarbonyl)-3-pyrrolidinone O-methyloxime Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid, 4(dimethylamino)butanoyl chloride, and piperidine the title compound was obtained in 100percent purity by LC/MS. MS(ESI+): m/z=339.2. A

Synthesize Find similar

Rx-ID: 23857900 Find similar reactions

Halazy, Serge; Quattropani, Anna; Bombrun, Agnes; Schwarz, Mattias; Thomas, Russel; Baxter, Anthony

Patent: US2003/171309 A1, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

Halazy, Serge; Quattropani, Anna; Scheer, Alexander; Schwarz, Mattias; Thomas, Russell; Baxter, Antony

Patent: US2003/212012 A1, 2003 ; Title/Abstract Full Text Show Details

253:(3EZ,5S)-1-(diphenylacetyl)-5-(1-piperidinylcarbonyl)-3-pyrrolidinone O-(4-methoxybenzyl)oxime

Example 253 (3EZ,5S)-1-(diphenylacetyl)-5-(1-piperidinylcarbonyl)-3-pyrrolidinone O-(4-methoxybenzyl)oxime Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-{[(4-methoxybenzyl)oxy]imino}-2-pyrrolidinecarboxylic acid, diphenylacetyl chloride, and piperidine the title compound was obtained in 87percent purity by LC/MS. MS(ESI+): m/z=526.4.

Synthesize Find similar

Rx-ID: 23915972 Find similar reactions

With triethylamine in dichloromethane

Hide Experimental Procedure

Synthesize Find similar

Schering Corporation

Patent: US2003/8877 A1, 2003 ; Title/Abstract Full Text Show Details

3:EXAMPLE 3

Oxalyl chloride (1.6 ml, 17.8 mmol) was added dropwise to the solution at -40° C. The solution was stirred at that temperature for 0.75 h. The alcohol 12(3.7 g, 11.9 mmol) in CH2Cl2 was added to the reaction mixture at -40° C. The resulting solution was stirred at that temperature for 0.75 h. Et3N (5.0 ml, 35.7 mmol) was added to the reaction mixture at -40° C. The white slurry was stirred at -40° C. for 0.5 h. The mixture was diluted with CH2Cl2 and washed with 1 N NaOH. The aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4), filtered, and concentrated to obtain 3.5 g (95percent) of aldehyde 13as a yellow oil. The piperazine 14a (133 mg, 0.65 mmol), aldehyde 13(200 mg, 0.65 mmol), and Na(AcO)3BH (165 mg, 0.78 mmol) were taken up in CH2Cl2 and stirred at 25° C. for 20 h. The solution was diluted with CH2Cl2 and washed with 1 N NaOH. The aqueous layer was extracted with CH2Cl2. The combined CH2Cl2 layers were dried (Na2SO4), filtered, and concentrated. Purification via preparative thin-layer chromatography (1/1 hexanes/acetone, SiO2) gave 160 mg (46percent) of 15a as an oil. The Boc group in 15a was removed, and the resulting piperidine was coupled to the pyrimidine acid as described in Scheme A, Step 4, to obtain the title compound as an oil: HRMS (MH+) found: 535.3765. Other R1 derivatives can be prepared via deprotection of the 4-methoxy benzyl group and subsequent derivatization as described previously in Scheme A.

Synthesize Find similar

With potassium hydroxide in hydrogenchloride; ethanol

Rx-ID: 23922073 Find similar reactions

Chen, Jian Jeffrey; Dunn, James Patrick; Goldstein, David Michael; Stahl, Christoph Martin

Patent: US2003/171584 A1, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

111.C:Step C

was isolated as the hydrochloride salt (mp 184.0-210.3° C.). 1.03 g of this ethyl carbamate (2.26 mmol) and potassium hydroxide (4.81 g, 85.7 mmol) in 60 ml ethanol was refluxed for 3 days and evaporated in vacuo. The residue was dissolved in aqueous hydrochloric acid (2M) and extracted with dichloromethane (2*), then chilled in an ice bath and re-alkalized with solid sodium hydroxide. The resultant oily precipitate was decanted and washed with methanol and dichloromethane, dried with sodium carbonate, and evaporated in vacuo to yield 0.550 g of the desired piperidine. A

Synthesize Find similar

Hide Experimental Procedure

Rx-ID: 24074896 Find similar reactions

LULY, JAY R.; NAKASATO, YOSHISUKE; OHSHIMA, ETSUO; SONE, HIROKI; KOTERA, OSAMU; HARRIMAN, GERALDINE C.B.

Patent: US2002/119973 A1, 2002 ; Title/Abstract Full Text Show Details

185:4-(7-Chloro-1,2-benzisoxazol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine

EXAMPLE 185 4-(7-Chloro-1,2-benzisoxazol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloro-1,2-benzisoxazol-3-yl) piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 28:761-769 (1985). 1H-NMR (CDCl ) d: 1.94-2.20 (6H,m), 2.30-2.60 (4H,m), 2.86-3.14 (3H,m), 3.79 (3H,s), 5.29 (2H,brs), 6.10 (1H,t), 6.70-6.88 (3H,m), 7.22 (1H,t), 7.27 (1H,dd), 7.50 (1H,dd), 7.57-7.68 (2H,m), 8.49 (1H,dd). 3

Hide Experimental Procedure

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6509346 B2, 2003 ; Title/Abstract Full Text Show Details

185:4-(7-Chloro-1,2-benzisoxazol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine

EXAMPLE 185 4-(7-Chloro-1,2-benzisoxazol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloro-1,2-benzisoxazol-3-yl) piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 28:761-769 (1985). 1H-NMR (CDCl ) δ: 1.94-2.20 (6H, m), 2.30-2.60 (4H, m), 2.86-3.14 (3H, m), 3.79 (3H, s), 5.29 (2H, brs), 6.10 (1H, t), 6.70-6.88 (3H, m), 7.22 (1H, t), 7.27 (1H, dd), 7.50 (1H, dd), 7.57-7.68 (2H, m), 8.49 (1H, dd). 3

Millennium Pharmaceuticals, Inc.; Kyowa Hakko Kogyo Co., Ltd.

Patent: US6329385 B1, 2001 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

185:4-(7-Chloro-1,2-benzisoxazol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine

Example 185 4-(7-Chloro-1,2-benzisoxazol-3-yl)-1-[3-(5,11-dihydro-7-methoxy[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidine The titled compound was prepared by following the procedure of example 45, step 3, but replacing 4-(4-chlorophenyl)-4-hydroxypiperidine with 4-(7-chloro-1,2-benzisoxazol-3-yl) piperidine. This piperidine was prepared by the same method described in J. Med. Chem. 28:761-769 (1985). 1H-NMR (CDCl ) δ: 1.94-2.20(6H,m), 2.30-2.60(4H,m), 2.86-3.14(3H,m), 3.79(3H,s), 5.29(2H,brs), 6.10(1H,t), 6.70-6.88(3H,m), 7.22(1H,t), 7.27(1H,dd), 7.50(1H,dd), 7.57-7.68(2H,m), 8.49(1H,dd). 3 A

Synthesize Find similar

Rx-ID: 24145402 Find similar reactions

H. Lundbeck A/S

Patent: US6514993 B1, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

6:3-(4-Fluorophenyl)-1-[4-[4-[2-(2-propyloxy)phenyl]-1-piperidinyl]butan-1-yl]-2-imidazolidinone, Oxalate 6a

A mixture of the thus isolated 1-unsubstituted piperidine (2.5 g), 1-(4-chloro-1-butyl)-3-(4-fluorophenyl)-2-imidazolidinone 2a (3.0 g), potassium carbonate (1.6 g), and potassium iodide (0.5 g) in MIBK (50 ml) was refluxed overnight.

H. Lundbeck A/S

Patent: US6514993 B1, 2003 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

7:3-(4-Fluorophenyl)-1-[4-[4-[2-(2-trifluoromethylsulfonyloxy)phenyl]-1-piperidinyl]butan-1-yl]-2-imidazolidinone 7a

A mixture of the thus isolated 1-unsubstituted piperidine (5.5 g), 1-(4-chloro-1-butyl)-3-(4-fluorophenyl)-2-imidazolidinone 2a (4.0 g), and potassium iodide (0.5 g) in MIBK (80 ml) was refluxed overnight. MIBK was evaporated in vacuo. A

Synthesize Find similar

A: 18%

Hide Experimental Procedure

12:Cbz-L-Leu-L-Phe-D-(N-Ac-amino-Ala)-C(O)-Piperidine

Example 12

Rx-ID: 24145403 Find similar reactions

Agouron Pharmaceuticals, Inc.

Patent: US6534530 B1, 2003 ; Title/Abstract Full Text Show Details

Cbz-L-Leu-L-Phe-D-(N-Ac-amino-Ala)-C(O)-Piperidine As a byproduct of the synthesis of compound 11, Cbz-L-Leu-L-Phe-D-(N-Ac-amino-Ala)-C(O)-piperidine (16.7 mg, 18percent yield) was obtained as a colorless, crystalline solid. Rf=0.36 (5percent CH3OH in CH2Cl2). IR (cm-1) 3310, 1651, 1537. 1H NMR (CDCl3) Î´0.88 (br s, 6H), 1.39-1.82 (m, 8H), 1.93 (s, 3H), 2.99-3.02 (m, 1H), 3.15-3.22 (m, 1 H), 3.40-3.75 (m, 6H), 4.07-4.12 (m, 21H), 5.07-5.18 (m, 4H), 6.27-6.57 (2 m, 2H), 7.18-7.36 (m, 10H), 7.53-7.60 (m, 2H). MS (FAB) 636 (MH+)