Query Query O
Results
Date
72 reactions in Reaxys
2017-11-14 06h:01m:12s (EST)
O
1. Query
O N
GH GH
Search as: Product, As drawn )
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O
O O
N
O
O
O
O
O
N O
O O
Rx-ID: 4691440 View in Reaxys 1/72 Yield 89%
Conditions & References With lithium hexamethyldisilazane in tetrahydrofuran, Time= 4h, T= -78 - -30 °C , Dieckmann Condensation Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
76 %
With potassium tert-butylate in toluene, Time= 0.5h, T= 0 °C Knight, David W.; Sibley, A. William; Journal of the Chemical Society - Perkin Transactions 1; nb. 15; (1997); p. 2179 - 2187 View in Reaxys
71 %
With lithium hexamethyldisilazane in tetrahydrofuran, Time= 4h, T= -78 °C Greshock, Thomas J.; Williams, Robert M.; Organic Letters; vol. 9; nb. 21; (2007); p. 4255 - 4258 View in Reaxys
60 %
With potassium tert-butylate in toluene, Time= 4h, T= -5 °C Haddad, Mansour; Larcheveque, Marc; Tetrahedron Asymmetry; vol. 16; nb. 13; (2005); p. 2243 - 2247 View in Reaxys
45 %
With potassium tert-butylate in toluene, Time= 2h, T= 0 °C Tran, Joe A.; Tucci, Fabio C.; Arellano, Melissa; Jiang, Wanlong; Chen, Caroline W.; Marinkovic, Dragan; Fleck, Beth A.; Wen, Jenny; Foster, Alan C.; Chen, Chen; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 6; (2008); p. 1931 - 1938 View in Reaxys
41 %
4.1.18. (R/S)-1-tert-Butyl 2-ethyl 3-oxopyrrolidine-1,2-dicarboxylate (31) To a suspension of potassium tert-butoxide (791 mg, 7.05 mmol) in anhydrous toluene (19 mL) at 10 C a solution of 30 (1.43 g, 4.7 mmol) in toluenewas added dropwise. The reactionwas stirred at 0 C for 90 min and then it was quenched with acetic acid (500 mL), followed by the addition of a cold solution of NaH2-PO4USDH2O (2.5 g) in 25 mL of water. The layers were separated, and the aqueous phase was extracted with CHCl3. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, pet. ether/EtOAc 5:1, Rf 0.44) obtaining the title compound 31 as a yellow oil (497 mg, 41percent yield). 1H NMR (CDCl3, 200 MHz) major rotamer: d 4.55 and 4.47 (s, 1H), 4.27-4.22 (m, 2H), 3.91-3.84 (m) and 3.82 (t, J = 8.2 Hz) 2H, 2.69 (t, J = 8.0 Hz, 2H), 1.49 and 1.43 (s, 9H), 1.30 (t, J = 7.1 Hz, 3H). Anal. C12H19NO5 (C, H, N). With potassium tert-butylate in toluene, Time= 1.5h, T= -10 - 0 °C , Inert atmosphere Calugi, Chiara; Trabocchi, Andrea; Lalli, Claudia; Guarna, Antonio; European Journal of Medicinal Chemistry; vol. 56; (2012); p. 96 - 107 View in Reaxys
37 %
With potassium tert-butylate in toluene, Time= 1.41667h, T= 0 °C , Dieckmann cyclization Williams, Robert M.; Cao, Jianhua; Tsujishima, Hidekazu; Cox, Rhona J.; Journal of the American Chemical Society; vol. 125; nb. 40; (2003); p. 12172 - 12178 View in Reaxys
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O
O O N O
O
O
O
H
N N H
OH
O
O
O
NH O
HN O
O
O
Rx-ID: 40536801 View in Reaxys 2/72 Yield
Conditions & References
72 %
Ethyl1-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanoyl)-3-oxopyrrolidine-2-carboxylate(6a)To asolution of LCbz-PheOH (600mg, 2.0 mmol) in THF (15 mL) at 0C was added DMAP(single crystal) followed by EDC.HCl (421mg, 2.2 mmol). The reaction mixturewas stirred for 10 min at 0C. Thereafter the deprotected product 4(612 mg, 2.0mmol) in THF (5.0 mL) wasadded to the reaction mixture and allowed to stir at 0C for another 10 minsand thereafter at room temperature for 12 h.After completion of the reaction, thesolvent was evaporated and the crude product purified using column chromatography(EtOAc/hexane, 30:70) to afford the product (72percent). 1H NMR (400 MHz,CDCl3): δ 7.32-7.03 (m, 10H), 5.80 (s, 1H), 5.22-4.87 (m, 2H),4.80-4.67 (m, 1H), 4.62-4.44 (s, 1H), 4.22-3.65 (m, 3H), 3.63-3.36 (m, 1H),3.20-2.94 (m, 1H), 2.91-2.77 (m, 1H), 2.63-2.44 (m, 1H), 2.40-1.91 (m, 1H),1.22-1.07 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 202.7, 171.4,170.9, 165.0, 164.8, 155.9, 136.3, 135.8, 129.6, 129.3, 128.7, 128.1, 127.3,67.0, 66.9, 65.1, 64.9, 52.7, 42.7, 40.0, 38.7, 37.0, 14.1. HRMS (ESI+) m/z calcd. for C24H27N2O6:439.1863; found [M+H] 439.1859. Stage 1: With dmap, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in tetrahydrofuran, Time= 0.166667h, T= 0 °C Stage 2: in tetrahydrofuran, Time= 12.3333h, T= 0 - 20 °C Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
O OO
O
OH
O
O
N HN
H
O
N N H
O
O
O
O HN
O
O
O
Rx-ID: 40536803 View in Reaxys 3/72 Yield 72 %
Conditions & References Ethyl1-((S)-2-((tert-butoxycarbonyl)amino)-3-phenylpropanoyl)-3-oxopyrrolidine-2-carboxylate(6b)To solution of LBoc-PheOH (530 mg, 2.0 mmol)and deprotected product4(612 mg, 2.0mmol)in DMF (10 mL) at 0C was added DIPEA (0.8 mL, 4.4 mmol) followed by HATU (836mg, 2.2 mmol). The reaction mixture was stirred for 10 min at 0C, then at roomtemperature for 10 h. After completion of the reaction, EtOAc (20 mL) was addedand the organic layer was washed with 1N HCl (15 mL) followed by dilute sodiumbicarbonate solution (15 mL) and brine (10 mL). The organic layer was driedusing anhydrous magnesium sulphate and the solvent was evaporated in vacouand the crude product purifiedusing column chromatography (EtOAc/hexane, 25:75) to afford the product (72percent). 1HNMR (400 MHz, CDCl3): δ 7.72-7.14 (m, 5H), 5.45-5.40 (m, 1H),4.81-4.72 (m, 1H), 4.26-4.19 (m, 2H), 3.85-3.71 (m, 1H), 3.54-3.46 (m, 2H),3.23-2.91 (m, 2H), 2.53-2.44 (m, 1H), 2.16-1.97 (m, 1H), 1.44-1.32 (m, 9H),1.29-1.26 (m, 3H); NMR (100 MHz, CDCl3): δ 202.6, 171.2,165.1, 155.0, 136.2, 129.4, 128.6, 127.2, 71.7, 64.8, 62.4, 52.2, 42.6,
13C
40.4,37.1, 28.3, 14.0.HRMS (ESI+) m/z calcd. for C21H29N2O6:405.2006; found [M+H] 405.2020. With N-ethyl-N,N-diisopropylamine, N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-Nmethylmethanaminium hexafluorophosphate in N,N-dimethyl-formamide, Time= 10.1667h, T= 0 - 20 °C Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174
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View in Reaxys
O
O
OH
N N H
O
O
O
N O
H O
O
O
O
NH
HN O
O
O
O
Rx-ID: 40536805 View in Reaxys 4/72 Yield
Conditions & References
70 %
Ethyl1-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropanoyl)-3-oxopyrrolidine-2-carboxylate(6c)Tosolution of L-Fmoc-PheOH (774 mg, 2.0 mmol) in THF (15 mL) at 0C was addedDMAP (single crystal) followed by EDC.HCl (421 mg, 2.2 mmol) and the reactionmixture was stirred for 10 min at 0C, thereafter the deprotected product4(612 mg, 2.0mmol) in THF (5.0 mL) wasadded to the reaction mixture and allowed to stir at 0C for another 10 minsand thereafter at room temperature for 12 h. After completion of the reaction,solvent was evapouratedin vacou and thecrude product purifiedusing column chromatography (EtOAc/hexane, 25:75) toafford the product (70percent). 1H NMR (400 MHz, CDCl ): δ7.80-7.76 (m, 2H), 7.62-7.53 (m, 2H), 7.44-7.39 (m, 2H), 7.35-7.26 (m, 5H),5.74-5.57 3 (m, 1H), 4.90-4.82 (m, 1H), 4.41-4.09 (m, 6H), 3.84-3.46 (m, 2H),3.25-2.90 (m, 2H), 2.79-2.60 (m, 2H), 2.37-2.06 (m, 2H), 1.38-1.26 (m, 3H); 13CNMR (100 MHz, CDCl3): δ 202.5, 171.6, 164.9, 156.1, 143.7, 141.2, 135.9,129.8, 129.4, 129.3, 128.6, 128.5, 127.7, 127.4, 127.2, 127.1, 127.0, 120.0,67.1, 65.0, 62.2, 52.7, 46.6, 43.0, 40.9, 37.3, 13.4.HRMS (ESI+) m/z calcd. forC31H31N2O6: 527.2160; found [M+H] 527.2177. Stage 1: With dmap, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in tetrahydrofuran, Time= 0.166667h, T= 0 °C Stage 2: in tetrahydrofuran, Time= 12.3333h, T= 0 - 20 °C Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys O
O
O
O
O O
O
N H
O N N
N O O
Rx-ID: 11059959 View in Reaxys 5/72 Yield
Conditions & References With dirhodium tetraacetate in toluene, Time= 0.5h, T= 85 - 90 °C Moreau, Robert J.; Sorensen, Erik J.; Tetrahedron; vol. 63; nb. 28; (2007); p. 6446 - 6453 View in Reaxys
7.41 g
4.2. Synthesis of methyl N-(tert-butoxycarbonyl)-3-oxopyrrolidine-2-carboxylate, 5 General procedure: A solution of N-(tert-butoxycarbonyl)-β-alanine (6.00 g, 31.71 mmol) in anhydrous tetrahydrofuran (100 mL) under an argon atmosphere was treated with N,N'-carbonyldiimidazole (7.24 g, 38.05 mmol). After stirring at room temperature for 1 h, previously mixed magnesium chloride (3.00 g, 31.51 mmol) and monomethyl monopotassium malonate (9.84 g, 63.02 mmol) were added. The resulting mixture was kept under an argon atmosphere and was stirred at room temperature for an additional 18 h. The solvent was evaporated and the residue was dissolved in ethyl acetate (100 mL) and washed with 5percent aqueous KHSO4 (2*50 mL), 5percent aqueous NaHCO3 (2*50 mL) and brine (2*50 mL). The organic layer was dried over MgSO4, filtered and evaporated under reduced pressure to afford 6 as a pale yellow oil (7.70 g, 31.39 mmol). The crude compound was dissolved in anhydrous acetonitrile (100 mL), under an argon atmosphere, and 3-carboxybenzenesulfonyl azide (7.84 g, 34.53 mmol) was added in one portion, followed by triethylamine (13.13 mL, 94.17 mmol). The resulting mixture was stirred at room temperature for 1 h. The solvent was concentrated in vacuo and the residue was dissolved in diethyl ether (100
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mL) and washed with saturated aqueous NaHCO3 (2*50 mL), and saturated aqueous NH4Cl (2*50 mL). The organic layer was dried over MgSO4, filtered and evaporated under reduced pressure to afford 7 as an orange oil (8.35 g, 30.78 mmol) that was taken on without further purification. It was dissolved in anhydrous toluene (300 mL), under an argon atmosphere, and Rh2(OAc)4 (0.068 g, 0.15 mmol) was added. The reaction mixture was heated at 85-90 °C for approximately 30 min in a preheated oil bath. The solvent was evaporated to dryness and the residue was purified by column chromatography (eluent: hexanes/ethyl acetate 3:1) to afford pure 5 as a white solid (7.41 g, 30.47 mmol, 96percent overall yield). Mp 56 °C. IR (neat) ν 2979, 1772, 1745, 1707 cm-1. 1H NMR (CDCl3, 400 MHz) δ 1.39, 1.46 (two s, 9H), 2.59-2.76 (dd, 2H, J=8.4, 6.8 Hz), 3.66-3.94 (m, 5H), 4.46, 4.54 (two s, 1H).
13C
NMR (CDCl3,
100 MHz) δ (duplicate signals are observed for most carbons) 28.09, 28.19; 36.37, 37.06; 41.52, 42.17; 52.86, 53.00; 65.20, 65.60; 81.15; 153.75; 166.69; 204.52. HRMS (ESI) C11H17NNaO5 [M+Na]+: calcd 266.0999, found 266.1004. With dirhodium tetraacetate in toluene, Time= 0.5h, T= 85 - 90 °C , Inert atmosphere Rodriguez, Isabel; Calaza, M. Isabel; Jimenez, Ana I.; Cativiela, Carlos; Tetrahedron; vol. 68; nb. 47; (2012); p. 9578 - 9582,5 View in Reaxys 0.775 g
With dirhodium tetraacetate in toluene, T= 90 °C , Inert atmosphere Kong, Chen; Jana, Navendu; Jones, Crystalann; Driver, Tom G.; Journal of the American Chemical Society; vol. 138; nb. 40; (2016); p. 13271 - 13280 View in Reaxys
O O O
O N H
O
O
O O
N
N O O
N
Rx-ID: 42407775 View in Reaxys 6/72 Yield 14.65 g
Conditions & References 1 : Compound (h):l-benzyl 2-(tert-butyl) 3-oxopyrrolidine-l,2-dicarboxylate. Compound (h):l-benzyl 2-(tert-butyl) 3-oxopyrrolidine-l,2-dicarboxylate. To a solution of the crude diazo β-keto ester, Compound (g) (17.5 g, 50.41 mmol, 1 equiv) in toluene (500 mL) was added Rh2(OAc)4 (111 mg, 0.252 mmol, 0.005 equiv). The mixture was stirred for lh at 90°C under argon and then concentrated in vacuo. The crude residue was diluted with diethyl ether and filtered trough Celite ®. The resulting filtrate was concentrated to afford 1 -benzyl 2-(tert-butyl) 3-oxopyrrolidine-l,2-dicarboxylate, Compound (h), as a yellow solid (14.65 g, 45.87 mmol, 91percent). Compound (h) could be used without further purification. 1H NMR (400MHz ,CHLOROFORM-d) δ = 7.44 - 7.28 (m, 5 H), 5.30 - 5.09 (m, 2 H), 4.53 - 4.43 (m, 1 H), 4.06 - 3.91 (m, 1 H), 3.91 - 3.79 (m, 1 H), 2.72 - 2.65 (m, 2 H), 1.48 - 1.37 (m, 9 H); 13C NMR (101 MHz , CDC13) δ = 204.4, 203.9, 164.9, 164.8, 154.6, 154.6, 136.1, 135.8, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 83.3, 83.2, 67.5, 66.2, 66.0, 42.1, 36.8, 36.1, 27.8, 27.7; IR: 1766, 1735, 1701, 1402, 1152, 1100; mp 54-56°C; HRMS (ESI) m/z [M + Na +] calcd for Ci7H2iNNa05, 342.1317; found, 342.1320. With dirhodium tetraacetate in toluene, Time= 1h, T= 90 °C , Inert atmosphere Patent; EOLAS THERAPEUTICS, INC.; KAMENECKA, Theodore M.; HE, Yuanjun; (105 pag.); WO2016/25669; (2016); (A1) English View in Reaxys To a solution of diazo β-keto ester 26 (98.4 g, 283.4 mmol, 1 equiv) in anhydrous toluene (2 L) under argon was added Rh2(OAc)4 (626mg, 1.47 mmol, 0.005 equiv). The mixture was stirred at 90°C for 1h and thenconcentrated in vacuo. Thecorresponding crude residue was taken up in diethyl ether and filtered throughCelite®. The filtrate was concentrated to afford 1-benzyl2-(tert-butyl) 3-oxopyrrolidine-1,2-dicarboxylate 27 as a yellow solid (82.4 g, 258 mmol, 91percent). Crude compound 27 was used without furtherpurification. 1H NMR (400 MHz, CDCl3) δ = 7.44 7.28 (m,5 H), 5.30 - 5.09 (m, 2 H), 4.50 (s, 0.4 H), 4.46 (s, 0.6 H), 4.06 - 3.91 (m, 1H), 3.91 - 3.79 (m, 1 H), 2.72 2.65 (m, 2 H), 1.48 - 1.37 (m, 9 H); 13CNMR (101 MHz, CDCl3) δ = 204.4, 203.9, 164.9, 164.8, 154.6, 154.6,136.1,
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135.8, 128.5, 128.4, 128.2, 128.1, 128.0, 127.9, 83.3, 83.2, 67.5, 66.2,66.0, 42.1, 36.8, 36.1, 27.8, 27.7; IR: 1766, 1735, 1701, 1402, 1152, 1100; mp 54-56°C; HRMS (ESI)m/z [M + Na+] calcd for C17H21NNaO5,342.1317; found, 342.1320. With dirhodium tetraacetate in toluene, Time= 1h, T= 90 °C , Inert atmosphere Doebelin, Christelle; He, Yuanjun; Kamenecka, Theodore M.; Tetrahedron Letters; vol. 57; nb. 50; (2016); p. 5658 - 5660 View in Reaxys O
N O O
2H
N H
O
N
2
H
O
2H
O
N O
2H
O
O
Rx-ID: 39077770 View in Reaxys 7/72 Yield
Conditions & References General procedure: To a solution of Intermediate 91c (2.66 g, 8.89 mmol) in toluene (100 mL) is addedrhodium (II) acetate dimer (19.6 mg, 0.04 mmol) and the mixture is heated to 100 °C for 4 hours. The mixture is then cooled to room temperature and the solvent is removed in vacuo. The crude material is dissolved in diethyl ether and the mixture is filtered through Celite. Evaporation of the solvent and purification of the crude material by flash chromatography (hexanes/ethyl acetate gradient) affords 1-tert-butyl 2-methyl 5,5-dimethyl-3-oxopyrrolidine-1,2-dicarboxylate 91d as a white solid. With dirhodium tetraacetate in toluene, Time= 4h, T= 100 °C Azimioara, Mihai; Alper, Phil; Cow, Christopher; Mutnick, Daniel; Nikulin, Victor; Lelais, Gerald; Mecom, John; McNeill, Matthew; Michellys, Pierre-Yves; Wang, Zhiliang; Reding, Esther; Paliotti, Michael; Li, Jing; Bao, Dingjiu; Zoll, Jocelyn; Kim, Young; Zimmerman, Matthew; Groessl, Todd; Tuntland, Tove; Joseph, Sean B.; McNamara, Peter; Seidel, H. Martin; Epple, Robert; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 23; (2014); p. 5478 - 5483 View in Reaxys
O O O O
O
O
O
O
N
N
N H
O
N
O
Rx-ID: 30546043 View in Reaxys 8/72 Yield
Conditions & References
99 %
With dirhodium tetraacetate in toluene, T= 110 °C , Inert atmosphere Hovey, M. Todd; Eklund, Emily J.; Pike, Robert D.; Mainkar, Anshul A.; Scheerer, Jonathan R.; Organic Letters; vol. 13; nb. 5; (2011); p. 1246 - 1249 View in Reaxys
O O
O
O
O
N
O
O
N O
O
O
O
Rx-ID: 9826463 View in Reaxys 9/72 Yield 71 %
Conditions & References With potassium tert-butylate in toluene, Time= 0.333333h, T= 0 °C
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Ooi, Takashi; Miki, Takashi; Maruoka, Keiji; Organic Letters; vol. 7; nb. 2; (2005); p. 191 - 193 View in Reaxys
O O O N H
O
O HCl
O
Cl
O
N
O
O
O
O O
Rx-ID: 43121544 View in Reaxys 10/72 Yield
Conditions & References
78%
Stage 1: With triethylamine in dichloromethane, Time= 0.166667h, T= 0 °C Stage 2: in dichloromethane, Time= 14h, T= 0 °C Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
O
O O
O
O
N
O
O
N
N
O
O
O
O
Rx-ID: 4279431 View in Reaxys 11/72 Yield
Conditions & References
73 %
With lithium hexamethyldisilazane in tetrahydrofuran, Time= 2h, T= -78 °C Sibi, Mukund P.; Christensen, James W.; Kim, Sung-Gyu; Eggen, Marijean; Stessman, Chad; Oien, Larry; Tetrahedron Letters; vol. 36; nb. 35; (1995); p. 6209 - 6212 View in Reaxys
73 %
Dieckman-type cyclization Pellegrini, Nadia; Schmitt, Martine; Guery, Sebastien; Bourguignon, Jean-Jacques; Tetrahedron Letters; vol. 43; nb. 17; (2002); p. 3243 - 3246 View in Reaxys
O
O O N
N
O O OH
Rx-ID: 8975603 View in Reaxys 12/72 Yield 90 %
Conditions & References With tetrapropylammonium perruthennate Kamenecka, Theodore M; Park, You-Jung; Lin, Linus S; Lanza Jr., Thomas; Hagmann, William K; Tetrahedron Letters; vol. 42; nb. 49; (2001); p. 8571 - 8573 View in Reaxys
0.99 g
Step 3. Preparation of B2-2: Step 3. Preparation of B2-2: Alcohol B2-1 (1.23 g, 3.18 mmol) and 2 g 4 A MS were suspended in DOM (16 mL) and treated with NMO (560 mg, 4.78 mmol) and TPAP (76 mg, 0.218 mmol). After stirring for 30 mm, the mixture was filteredover a short pad of silica and eluted off with 50percent EtOAc/Hex. The filtrate was concentrated and the crude residue was purified by silica gel chromatography (10percent to 30percent EtOAc/Hex to afford ketone B2-2 (0.99 g).
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With TPAP, 4-methylmorpholine N-oxide in dichloromethane, Time= 0.5h Patent; GILEAD SCIENCES, INC.; BJORNSON, Kyla; CANALES, Eda; COTTELL, Jeromy, J.; KARKI, Kapil, Kumar; KATANA, Ashley, Anne; KATO, Darryl; KOBAYASHI, Tetsuya; LINK, John, O.; MARTINEZ, Ruben; PHILLIPS, Barton, W.; PYUN, Hyung-jung; SANGI, Michael; SCHRIER, Adam, James; SIEGEL, Dustin; TAYLOR, James, G.; TRAN, Chinh, Viet; TREJO MARTIN, Teresa, Alejandra; VIVIAN, Randall, W.; YANG, ZhengYu; ZABLOCKI, Jeff; ZIPFEL, Sheila; WO2014/8285; (2014); (A1) English View in Reaxys O O
O
O
O
O
N H
N
O
O
N O
N
O
Rx-ID: 3667647 View in Reaxys 13/72 Yield
Conditions & References
90 %
With dirhodium tetraacetate in benzene, Heating Moyer, Mikel P.; Feldman, Paul L.; Rapoport, Henry; Journal of Organic Chemistry; vol. 50; nb. 25; (1985); p. 5223 - 5230 View in Reaxys
O
O
O
N O
O
N
N
O
O O
O O
Rx-ID: 8780671 View in Reaxys 14/72 Yield
Conditions & References
74 %, 13 %
With potassium tert-butylate in tetrahydrofuran, Time= 3h, T= -78 °C , Dieckmann cyclization Pinto, Americo C.; Abdala, Rodrigo V.; Costa, Paulo R.R.; Tetrahedron Asymmetry; vol. 11; nb. 21; (2000); p. 4239 - 4243 View in Reaxys
O
O
O
N O
O
N
N
O
O O
O O
Rx-ID: 8781314 View in Reaxys 15/72 Yield
Conditions & References
69 %, 9 %
With potassium tert-butylate in tetrahydrofuran, Time= 3h, T= -78 °C , Dieckmann cyclization Pinto, Americo C.; Abdala, Rodrigo V.; Costa, Paulo R.R.; Tetrahedron Asymmetry; vol. 11; nb. 21; (2000); p. 4239 - 4243 View in Reaxys O
O HO
O
O N H
O O
N O O
Rx-ID: 11603084 View in Reaxys 16/72
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Yield
Conditions & References Reaction Steps: 4 1: tetrahydrofuran / 4 h 2: MgCl2 / tetrahydrofuran / 20 °C 3: triethylamine; 3-carboxybenzenesulfonyl azide / acetonitrile / 20 °C 4: Rh2(OAc)4 / toluene / 0.5 h / 85 - 90 °C With triethylamine, magnesium chloride, dirhodium tetraacetate in tetrahydrofuran, toluene, acetonitrile Moreau, Robert J.; Sorensen, Erik J.; Tetrahedron; vol. 63; nb. 28; (2007); p. 6446 - 6453 View in Reaxys Reaction Steps: 3 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h / 20 °C / |Inert atmosphere 1.2: 18 h / 20 °C / |Inert atmosphere 2.1: 3-carbonxybenzenesulfonyl azide; triethylamine / acetonitrile / 1 h / 20 °C / |Inert atmosphere 3.1: dirhodium tetraacetate / toluene / 0.5 h / 85 - 90 °C / |Inert atmosphere With dirhodium tetraacetate, 3-carbonxybenzenesulfonyl azide, triethylamine, 1,1'-carbonyldiimidazole in tetrahydrofuran, toluene, acetonitrile, 1.2: |Claisen Condensation Rodriguez, Isabel; Calaza, M. Isabel; Jimenez, Ana I.; Cativiela, Carlos; Tetrahedron; vol. 68; nb. 47; (2012); p. 9578 - 9582,5 View in Reaxys Reaction Steps: 3 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 4 h / |Inert atmosphere 1.2: 15 h / |Inert atmosphere 2.1: triethylamine; 3-carbonxybenzenesulfonyl azide / acetonitrile / 1.5 h / |Inert atmosphere 3.1: dirhodium tetraacetate / toluene / 90 °C / |Inert atmosphere With dirhodium tetraacetate, 3-carbonxybenzenesulfonyl azide, triethylamine, 1,1'-carbonyldiimidazole in tetrahydrofuran, toluene, acetonitrile Kong, Chen; Jana, Navendu; Jones, Crystalann; Driver, Tom G.; Journal of the American Chemical Society; vol. 138; nb. 40; (2016); p. 13271 - 13280 View in Reaxys O
O O
O
O
O N H
O O
N O O
Rx-ID: 11612829 View in Reaxys 17/72 Yield
Conditions & References Reaction Steps: 2 1: triethylamine; 3-carboxybenzenesulfonyl azide / acetonitrile / 20 °C 2: Rh2(OAc)4 / toluene / 0.5 h / 85 - 90 °C With triethylamine, dirhodium tetraacetate in toluene, acetonitrile Moreau, Robert J.; Sorensen, Erik J.; Tetrahedron; vol. 63; nb. 28; (2007); p. 6446 - 6453 View in Reaxys Reaction Steps: 2 1: 3-carbonxybenzenesulfonyl azide; triethylamine / acetonitrile / 1 h / 20 °C / |Inert atmosphere 2: dirhodium tetraacetate / toluene / 0.5 h / 85 - 90 °C / |Inert atmosphere With dirhodium tetraacetate, 3-carbonxybenzenesulfonyl azide, triethylamine in toluene, acetonitrile Rodriguez, Isabel; Calaza, M. Isabel; Jimenez, Ana I.; Cativiela, Carlos; Tetrahedron; vol. 68; nb. 47; (2012); p. 9578 - 9582,5 View in Reaxys Reaction Steps: 2 1: triethylamine; 3-carbonxybenzenesulfonyl azide / acetonitrile / 1.5 h / |Inert atmosphere
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2: dirhodium tetraacetate / toluene / 90 °C / |Inert atmosphere With dirhodium tetraacetate, 3-carbonxybenzenesulfonyl azide, triethylamine in toluene, acetonitrile Kong, Chen; Jana, Navendu; Jones, Crystalann; Driver, Tom G.; Journal of the American Chemical Society; vol. 138; nb. 40; (2016); p. 13271 - 13280 View in Reaxys
O
O
O
O
O
N H
O
N
O
O O
Rx-ID: 14033926 View in Reaxys 18/72 Yield
Conditions & References Reaction Steps: 2 1: 90 percent / aq. NaOH / CHCl3 / 11 h / 0 - 20 °C 2: 37 percent / t-BuOK / toluene / 1.42 h / 0 °C With sodium hydroxide, potassium tert-butylate in chloroform, toluene, 2: Dieckmann cyclization Williams, Robert M.; Cao, Jianhua; Tsujishima, Hidekazu; Cox, Rhona J.; Journal of the American Chemical Society; vol. 125; nb. 40; (2003); p. 12172 - 12178 View in Reaxys Reaction Steps: 2 1: 98 percent / Et3N / CH2Cl2 / 2 h / Ambient temperature 2: 45 percent / t-BuOK / toluene / 0.5 h / 0 °C With potassium tert-butylate, triethylamine in dichloromethane, toluene Cooper, Jeremy; Gallagher, Peter T.; Knight, David W.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb. 12; (1993); p. 1313 - 1318 View in Reaxys Reaction Steps: 2 1: sodium hydroxide / chloroform; water / 73 h / 0 - 20 °C 2: potassium tert-butylate / toluene / 1.5 h / -10 - 0 °C / |Inert atmosphere With potassium tert-butylate, sodium hydroxide in chloroform, water, toluene Calugi, Chiara; Trabocchi, Andrea; Lalli, Claudia; Guarna, Antonio; European Journal of Medicinal Chemistry; vol. 56; (2012); p. 96 - 107 View in Reaxys
O O
O
-3 (v1)
O O
O
3 Na +
N O
(v1)
O
O
O
P OO
(v1)
N O O
O
Rx-ID: 24889246 View in Reaxys 19/72 Yield
Conditions & References 36 : EXAMPLE 36 A solution of 53.9 g of ethyl N-(ethoxycarbonylmethyl)-N-(ethoxycarbonyl)-β-alaninate in 200 ml of toluene is added dropwise to a stirred solution of potassium hexamethyldisilazide (429 ml, 0,653M) in 125 ml of toluene under nitrogen and cooled to 0°. After 45 minutes at 0°, 21.6 ml of acetic acid is added followed by a solution of 100 g of sodium phosphate (monobasic) in 1 liter of water. The layers are separated, the organic layer is washed with pH 7 buffer, dried over sodium sulfate, filtered, concentrated and purified by flash chromatography using ethyl acetate/hexane (3:7) to yield ethyl 1-ethoxycarbonyl-3-oxo-pyrrolidine-2-carboxylate.
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With potassium hexamethylsilazane, acetic acid in water, toluene Patent; Ciba-Geigy Corporation; US4906621; (1990); (A1) English View in Reaxys
O
O
O O O
O N
N
O
O S
O O
Rx-ID: 2569097 View in Reaxys 20/72 Yield
Conditions & References
77 %
With sodium hydride in tetrahydrofuran, Ambient temperature Yamada, Yasuji; Ishii, Toshihide; Kimura, Masayuki; Hosaka, Kunio; Tetrahedron Letters; vol. 22; nb. 14; (1981); p. 1353 - 1354 View in Reaxys
77 %
Dieckman-type cyclization Pellegrini, Nadia; Schmitt, Martine; Guery, Sebastien; Bourguignon, Jean-Jacques; Tetrahedron Letters; vol. 43; nb. 17; (2002); p. 3243 - 3246 View in Reaxys O
O
O O
O
O O
N
N
O
O
Rx-ID: 3614320 View in Reaxys 21/72 Yield
Conditions & References
65 %
With sodium hydride, oil in toluene, Time= 14h, T= 25 °C McHugh, Michael; Proctor, George R.; Journal of Chemical Research, Miniprint; nb. 8; (1984); p. 2230 - 2253 View in Reaxys O
O
N
O
O
O N
O
O
O
O
O
O
O
N
O O
O O
Rx-ID: 4699152 View in Reaxys 22/72 Yield 60 %
Conditions & References With potassium tert-butylate in toluene, Time= 0.5h, T= 0 °C , Yields of byproduct given Knight, David W.; Sibley, A. William; Journal of the Chemical Society - Perkin Transactions 1; nb. 15; (1997); p. 2179 - 2187 View in Reaxys
60 %
With potassium tert-butylate in toluene, Time= 0.5h, T= 0 °C , Yield given Knight, David W.; Sibley, A. William; Journal of the Chemical Society - Perkin Transactions 1; nb. 15; (1997); p. 2179 - 2187 View in Reaxys
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O O O
O
O
O O
N
O
O O
Rx-ID: 14035567 View in Reaxys 23/72 Yield
Conditions & References Reaction Steps: 2 1: 90 percent / aq. NaOH / CHCl3 / 11 h / 0 - 20 °C 2: 37 percent / t-BuOK / toluene / 1.42 h / 0 °C With sodium hydroxide, potassium tert-butylate in chloroform, toluene, 2: Dieckmann cyclization Williams, Robert M.; Cao, Jianhua; Tsujishima, Hidekazu; Cox, Rhona J.; Journal of the American Chemical Society; vol. 125; nb. 40; (2003); p. 12172 - 12178 View in Reaxys Reaction Steps: 2 1: 98 percent / Et3N / CH2Cl2 / 2 h / Ambient temperature 2: 45 percent / t-BuOK / toluene / 0.5 h / 0 °C With potassium tert-butylate, triethylamine in dichloromethane, toluene Cooper, Jeremy; Gallagher, Peter T.; Knight, David W.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb. 12; (1993); p. 1313 - 1318 View in Reaxys
O
OH
O Br–
O
O
P+
O
P
N
N
O OH
OH O
O
N O O
O
HO
Rx-ID: 24056271 View in Reaxys 24/72 Yield
Conditions & References 20 : Synthesis of Tert.Thiols Example 20 Synthesis of Tert.Thiols Oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester were prepared from BOC-Hyp-OH following literature procedure [Baldwin, Jack E.; Field, Robert A.; Lawrence, Christopher C.; Merritt, Kristen D.; Schofield, Christopher J.; Tetrahedron Lett.; 34; 1993; 7489-7492; and Herdewijn, Piet; Claes, Paul J.; Vanderhaeghe, Hubert; Can.J.Chem.; 60; 1982; 2903-2907;] To a solution of methylenetriphenyl phosphorane, previously prepared from 37 g (777 mmol, 50percent NaH in mineral oil, 4 eq) and 277.6 g (777 mmol, 4 eq) methyltriphenyl-phosphonium bromide in 1.5 1 THF by stirring at 50° C. for 4 h, were added 44.5 g (194 mmol, 1 eq) (2S)-4-Oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester in 300 ml over a period of 30 min at RT. With NaH in tetrahydrofuran, mineral oil Patent; Aebi, Johannes; Bur, Daniel; Chucholowski, Alexander; Dehmlow, Henrietta; Kitas, Eric Argirios; Obst, Ulrike; Wessel, Hans Peter; US2002/40146; (2002); (A1) English View in Reaxys
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O
O
O
O
O
HCl
N O
O
O
NH
Rx-ID: 43121510 View in Reaxys 25/72 Yield
Conditions & References With hydrogenchloride in diethyl ether, dichloromethane, Time= 8h, T= 20 °C Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
O O
N
O
O
O
O
O
O
O
O
N
N O
O
O
O
O
O
Rx-ID: 3457709 View in Reaxys 26/72 Yield
Conditions & References
43 %, 45 %
With potassium tert-butylate in toluene, Time= 0.5h, T= 0 °C Cooper, Jeremy; Gallagher, Peter T.; Knight, David W.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb. 12; (1993); p. 1313 - 1318 View in Reaxys
O
O O N
N O
OH O
Rx-ID: 22977653 View in Reaxys 27/72 Yield
Conditions & References 5 : Synthesis of the pro3 Monomer Class; Example 5 trans-3-Hydroxy-(L)-proline 39 is commercially available from Acros at $19/gram (2000/2001 catalog) and is the starting point for two diastereomeric members of the pro3 monomer class.First the carboxylate of 39 will be converted to the methyl ester 40 via a Fischer esterification.Next, the amine will be protected using the 9-phenyl-fluorenyl (PhF) group [32] to obtain 41.The alcohol will then be oxidized to the ketone 42 using a TPAP oxidation.This sequence is similar to that used by Kamenecka and co-workers in their enantioselective synthesis of 3-substituted prolines [33].The N-PhF group will protect the a-carbon from epimerization.A Bucherer-Bergs reaction is then carried out to form the two diastereomeric hydantoins 43 and 44.In the event that only one diastereomer is formed selectively, the two step Strecker/Bucherer-Bergs sequence suggested by Edward [34] can be used to obtain the second diastereomer.In either case, access to both diastereomers 43 and 44 is obtained.The diastereomeric hydantoins can be separated by chromatography as in the pro4 monomer class or separated by selective crystallization.The two diastereomeric hydantoins will be carried through independently to form two diastereomeric building blocks.If the hydantoins cannot be separated at this stage, the synthesis can continue with the mixture, with separation of the diastereomers at a later stage. With tetrapropylammonium perruthennate Patent; Schafmeister, Christian E.; US2004/77879; (2004); (A1) English View in Reaxys
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O
O O
O
O
N
O
O
N
Rx-ID: 9944245 View in Reaxys 28/72 Yield
Conditions & References With sodium hydride in toluene, Time= 3h, T= -5 °C , Dieckmann condensation Collina, Simona; Rossi, Daniela; Loddo, Guya; Barbieri, Annalisa; Lanza, Enrica; Linati, Laura; Alcaro, Stefano; Gallelli, Andrea; Azzolina, Ornella; Bioorganic and Medicinal Chemistry; vol. 13; nb. 9; (2005); p. 3117 - 3126 View in Reaxys
O O
O
O
O
HN
N O
O
O
N N
Rx-ID: 11618018 View in Reaxys 29/72 Yield
Conditions & References Reaction Steps: 3 1: MgCl2 / tetrahydrofuran / 20 °C 2: triethylamine; 3-carboxybenzenesulfonyl azide / acetonitrile / 20 °C 3: Rh2(OAc)4 / toluene / 0.5 h / 85 - 90 °C With triethylamine, magnesium chloride, dirhodium tetraacetate in tetrahydrofuran, toluene, acetonitrile Moreau, Robert J.; Sorensen, Erik J.; Tetrahedron; vol. 63; nb. 28; (2007); p. 6446 - 6453 View in Reaxys O O
N
O
O
O
O
O N
O
O
O O
Rx-ID: 8681077 View in Reaxys 30/72 Yield
Conditions & References With potassium tert-butylate in toluene, Time= 0.5h, T= 0 °C , Dickemann cyclization St-Denis; Tak Hang Chan; Canadian Journal of Chemistry; vol. 78; nb. 6; (2000); p. 776 - 783 View in Reaxys
O
O
O O N
O N O
O
O
Rx-ID: 30545909 View in Reaxys 31/72 Yield
Conditions & References Reaction Steps: 2 1: lithium hexamethyldisilazane / tetrahydrofuran / 3 h / -78 °C / Inert atmosphere 2: dirhodium tetraacetate / toluene / 110 °C / Inert atmosphere With dirhodium tetraacetate, lithium hexamethyldisilazane in tetrahydrofuran, toluene, 1: Claisen condensation
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Hovey, M. Todd; Eklund, Emily J.; Pike, Robert D.; Mainkar, Anshul A.; Scheerer, Jonathan R.; Organic Letters; vol. 13; nb. 5; (2011); p. 1246 - 1249 View in Reaxys
O O
N H
O
O
O
HCl
O
O NH
Rx-ID: 43121473 View in Reaxys 32/72 Yield
Conditions & References Reaction Steps: 3 1: sodium hydroxide / water; chloroform / 0 - 20 °C 2: lithium hexamethyldisilazane / tetrahydrofuran / 4 h / -78 - -30 °C 3: hydrogenchloride / dichloromethane; diethyl ether / 8 h / 20 °C With hydrogenchloride, sodium hydroxide, lithium hexamethyldisilazane in tetrahydrofuran, diethyl ether, dichloromethane, chloroform, water, 2: |Dieckmann Condensation Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
O
O
O O
N H
O
O
O
N
O O O
Rx-ID: 43121474 View in Reaxys 33/72 Yield
Conditions & References Reaction Steps: 4 1.1: sodium hydroxide / water; chloroform / 0 - 20 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 4 h / -78 - -30 °C 3.1: hydrogenchloride / dichloromethane; diethyl ether / 8 h / 20 °C 4.1: triethylamine / dichloromethane / 0.17 h / 0 °C 4.2: 14 h / 0 °C With hydrogenchloride, triethylamine, sodium hydroxide, lithium hexamethyldisilazane in tetrahydrofuran, diethyl ether, dichloromethane, chloroform, water, 2.1: |Dieckmann Condensation Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys O O
N
O
O
O
O
O
HCl O
O
NH
Rx-ID: 43121492 View in Reaxys 34/72 Yield
Conditions & References Reaction Steps: 2 1: lithium hexamethyldisilazane / tetrahydrofuran / 4 h / -78 - -30 °C 2: hydrogenchloride / dichloromethane; diethyl ether / 8 h / 20 °C With hydrogenchloride, lithium hexamethyldisilazane in tetrahydrofuran, diethyl ether, dichloromethane, 1: |Dieckmann Condensation Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274
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View in Reaxys O O
N
O
O
O
O
O
N
O
O
O
O O
Rx-ID: 43121493 View in Reaxys 35/72 Yield
Conditions & References Reaction Steps: 3 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 4 h / -78 - -30 °C 2.1: hydrogenchloride / dichloromethane; diethyl ether / 8 h / 20 °C 3.1: triethylamine / dichloromethane / 0.17 h / 0 °C 3.2: 14 h / 0 °C With hydrogenchloride, triethylamine, lithium hexamethyldisilazane in tetrahydrofuran, diethyl ether, dichloromethane, 1.1: |Dieckmann Condensation Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
O
O
O
O
O N
O
N
O
O
O
O O
Rx-ID: 43121511 View in Reaxys 36/72 Yield
Conditions & References Reaction Steps: 2 1.1: hydrogenchloride / dichloromethane; diethyl ether / 8 h / 20 °C 2.1: triethylamine / dichloromethane / 0.17 h / 0 °C 2.2: 14 h / 0 °C With hydrogenchloride, triethylamine in diethyl ether, dichloromethane Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
O O O O
N H
O
O
O
O
O
O O
N
O
O O
Rx-ID: 43121491 View in Reaxys 37/72 Yield
Conditions & References Reaction Steps: 2 1: sodium hydroxide / water; chloroform / 0 - 20 °C 2: lithium hexamethyldisilazane / tetrahydrofuran / 4 h / -78 - -30 °C With sodium hydroxide, lithium hexamethyldisilazane in tetrahydrofuran, chloroform, water, 2: |Dieckmann Condensation Dong, Shuai; Indukuri, Kiran; Clive, Derrick L. J.; Gao, Jin-Ming; Chemical Communications; vol. 52; nb. 53; (2016); p. 8271 - 8274 View in Reaxys
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O
O
O K+
O O
O
O N
N –
O
O
O O
O
O
O N O O
O
Rx-ID: 186851 View in Reaxys 38/72 Yield
Conditions & References With toluene Uchibayashi; Yakugaku Zasshi; vol. 78; (1958); p. 845,848; ; (1959); p. 331 View in Reaxys Blake et al.; Journal of the American Chemical Society; vol. 86; (1964); p. 5293,5298 View in Reaxys O
O O N
O
O
N
O
O
Rx-ID: 4098644 View in Reaxys 39/72 Yield
Conditions & References With sodium hydride in benzene, Heating Denmark, Scott E.; Forbes, David C.; Hays, David S.; DePue, Jeffrey S.; Wilde, Richard G.; Journal of Organic Chemistry; vol. 60; nb. 5; (1995); p. 1391 - 1407 View in Reaxys
O
O
OH
H N
O
O N
OH
Rx-ID: 15135525 View in Reaxys 40/72 Yield
Conditions & References Reaction Steps: 3 1: HCl 2: TMSCl; K2CO3 / methanol 3: 90 percent / (nPr)4NRuO4 With hydrogenchloride, chloro-trimethyl-silane, tetrapropylammonium perruthennate, potassium carbonate in methanol Kamenecka, Theodore M; Park, You-Jung; Lin, Linus S; Lanza Jr., Thomas; Hagmann, William K; Tetrahedron Letters; vol. 42; nb. 49; (2001); p. 8571 - 8573 View in Reaxys Reaction Steps: 2 1.1: thionyl chloride / methanol / 24 h / 0 - 20 °C 1.2: 0 - 20 °C
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2.1: 4-methylmorpholine N-oxide; TPAP / dichloromethane / 0.5 h With thionyl chloride, TPAP, 4-methylmorpholine N-oxide in methanol, dichloromethane Patent; GILEAD SCIENCES, INC.; BJORNSON, Kyla; CANALES, Eda; COTTELL, Jeromy, J.; KARKI, Kapil, Kumar; KATANA, Ashley, Anne; KATO, Darryl; KOBAYASHI, Tetsuya; LINK, John, O.; MARTINEZ, Ruben; PHILLIPS, Barton, W.; PYUN, Hyung-jung; SANGI, Michael; SCHRIER, Adam, James; SIEGEL, Dustin; TAYLOR, James, G.; TRAN, Chinh, Viet; TREJO MARTIN, Teresa, Alejandra; VIVIAN, Randall, W.; YANG, ZhengYu; ZABLOCKI, Jeff; ZIPFEL, Sheila; WO2014/8285; (2014); (A1) English View in Reaxys O
O O N
I
silver-salt of phosphoric acid-<2-benzyloxycarbonylamino-ethyl ester>-phenyl ester
Rx-ID: 18052192 View in Reaxys 41/72 Yield
Conditions & References Reaction Steps: 3 3: NaH / benzene / Heating With sodium hydride in benzene Denmark, Scott E.; Forbes, David C.; Hays, David S.; DePue, Jeffrey S.; Wilde, Richard G.; Journal of Organic Chemistry; vol. 60; nb. 5; (1995); p. 1391 - 1407 View in Reaxys O
O O N
O O
N H
Rx-ID: 18055978 View in Reaxys 42/72 Yield
Conditions & References Reaction Steps: 2 2: NaH / benzene / Heating With sodium hydride in benzene Denmark, Scott E.; Forbes, David C.; Hays, David S.; DePue, Jeffrey S.; Wilde, Richard G.; Journal of Organic Chemistry; vol. 60; nb. 5; (1995); p. 1391 - 1407 View in Reaxys
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O O O
O N H
O
O
O N
O
O O
Rx-ID: 42407764 View in Reaxys 43/72 Yield
Conditions & References Reaction Steps: 2 1: m-carboxybenzenesulfonyl azide; triethylamine / acetonitrile / 2 h / 25 °C / |Inert atmosphere 2: dirhodium tetraacetate / toluene / 1 h / 90 °C / |Inert atmosphere With dirhodium tetraacetate, m-carboxybenzenesulfonyl azide, triethylamine in toluene, acetonitrile Patent; EOLAS THERAPEUTICS, INC.; KAMENECKA, Theodore M.; HE, Yuanjun; (105 pag.); WO2016/25669; (2016); (A1) English View in Reaxys Reaction Steps: 2 1: m-carboxybenzenesulfonyl azide; triethylamine / acetonitrile / 2 h / 20 °C / |Inert atmosphere 2: dirhodium tetraacetate / toluene / 1 h / 90 °C / |Inert atmosphere With dirhodium tetraacetate, m-carboxybenzenesulfonyl azide, triethylamine in toluene, acetonitrile Doebelin, Christelle; He, Yuanjun; Kamenecka, Theodore M.; Tetrahedron Letters; vol. 57; nb. 50; (2016); p. 5658 - 5660 View in Reaxys
O O HO
O
O N H
O O
N O O
Rx-ID: 42407913 View in Reaxys 44/72 Yield
Conditions & References Reaction Steps: 3 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 18 h / 25 °C 1.2: 5.5 h / 0 - 40 °C 2.1: m-carboxybenzenesulfonyl azide; triethylamine / acetonitrile / 2 h / 25 °C / |Inert atmosphere 3.1: dirhodium tetraacetate / toluene / 1 h / 90 °C / |Inert atmosphere With dirhodium tetraacetate, m-carboxybenzenesulfonyl azide, triethylamine, 1,1'-carbonyldiimidazole in tetrahydrofuran, toluene, acetonitrile Patent; EOLAS THERAPEUTICS, INC.; KAMENECKA, Theodore M.; HE, Yuanjun; (105 pag.); WO2016/25669; (2016); (A1) English View in Reaxys Reaction Steps: 4 1.1: tetrahydrofuran / 18 h / 20 °C 2.1: isopropylmagnesium chloride / tetrahydrofuran / 3 h / 0 - 40 °C 2.2: 4 h / 0 - 20 °C 3.1: m-carboxybenzenesulfonyl azide; triethylamine / acetonitrile / 2 h / 20 °C / |Inert atmosphere 4.1: dirhodium tetraacetate / toluene / 1 h / 90 °C / |Inert atmosphere With dirhodium tetraacetate, m-carboxybenzenesulfonyl azide, isopropylmagnesium chloride, triethylamine in tetrahydrofuran, toluene, acetonitrile
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Doebelin, Christelle; He, Yuanjun; Kamenecka, Theodore M.; Tetrahedron Letters; vol. 57; nb. 50; (2016); p. 5658 - 5660 View in Reaxys
O
O
O
O
O
N O
O
O
N
HN
O
O
O
Rx-ID: 40536785 View in Reaxys 45/72 Yield
Conditions & References Reaction Steps: 3 1.1: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)urea / toluene / 24 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.17 h / 0 °C 3.2: 12.33 h / 0 - 20 °C With dmap, 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2yl)methyl)urea, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride, trifluoroacetic acid in tetrahydrofuran, dichloromethane, toluene, 1.1: |Michael Addition Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys Reaction Steps: 3 1.1: epi-cinchonidine / toluene / 24 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.17 h / 0 °C 3.2: 12.33 h / 0 - 20 °C With dmap, epi-cinchonidine, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride, trifluoroacetic acid in tetrahydrofuran, dichloromethane, toluene, 1.1: |Michael Addition Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
O
O
O
O
O
N
O
O
N
O
O O
HN O
Rx-ID: 40536786 View in Reaxys 46/72 Yield
Conditions & References Reaction Steps: 3 1: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)urea / toluene / 24 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 10.17 h / 0 - 20 °C With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)urea, N-ethyl-N,N-diisopropylamine, trifluoroacetic acid, N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyri-
Copyright © 2017 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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din-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate in dichloromethane, N,N-dimethyl-formamide, toluene, 1: |Michael Addition Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys Reaction Steps: 3 1: epi-cinchonidine / toluene / 24 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 10.17 h / 0 - 20 °C With epi-cinchonidine, N-ethyl-N,N-diisopropylamine, trifluoroacetic acid, N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate in dichloromethane, N,N-dimethylformamide, toluene, 1: |Michael Addition Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
O
O
O
O O N O O
O N
HN
O
O
O
Rx-ID: 40536787 View in Reaxys 47/72 Yield
Conditions & References Reaction Steps: 3 1.1: 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)urea / toluene / 24 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.17 h / 0 °C 3.2: 12.33 h / 0 - 20 °C With dmap, 1-(3,5-bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2yl)methyl)urea, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride, trifluoroacetic acid in tetrahydrofuran, dichloromethane, toluene, 1.1: |Michael Addition Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys Reaction Steps: 3 1.1: epi-cinchonidine / toluene / 24 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.17 h / 0 °C 3.2: 12.33 h / 0 - 20 °C With dmap, epi-cinchonidine, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride, trifluoroacetic acid in tetrahydrofuran, dichloromethane, toluene, 1.1: |Michael Addition Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
Copyright © 2017 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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O
O N
O
O
O
O
O N
O
O
Rx-ID: 4281184 View in Reaxys 48/72 Yield
Conditions & References With potassium tert-butylate in toluene, 1.) ice-water cooling, 1 h, 2.) room temp., 1 h Sunagawa; Matsumura; Sumita; Nouda; Journal of Antibiotics; vol. 48; nb. 5; (1995); p. 408 - 416 View in Reaxys
O
O
O
H N
O N
O OH
Rx-ID: 15140971 View in Reaxys 49/72 Yield
Conditions & References Reaction Steps: 2 1: TMSCl; K2CO3 / methanol 2: 90 percent / (nPr)4NRuO4 With chloro-trimethyl-silane, tetrapropylammonium perruthennate, potassium carbonate in methanol Kamenecka, Theodore M; Park, You-Jung; Lin, Linus S; Lanza Jr., Thomas; Hagmann, William K; Tetrahedron Letters; vol. 42; nb. 49; (2001); p. 8571 - 8573 View in Reaxys
O
O
O O
O
N H
N
Rx-ID: 15426145 View in Reaxys 50/72 Yield
Conditions & References Reaction Steps: 2 1: 86 percent / aq. Na2CO3 / tetrahydrofuran / 14 h / Heating 2: 13 percent / t-BuOK / tetrahydrofuran / 3 h / -78 °C With potassium tert-butylate, sodium carbonate in tetrahydrofuran, 2: Dieckmann cyclization Pinto, Americo C.; Abdala, Rodrigo V.; Costa, Paulo R.R.; Tetrahedron Asymmetry; vol. 11; nb. 21; (2000); p. 4239 - 4243 View in Reaxys
O
O
O O
N H
O N
Rx-ID: 15426146 View in Reaxys 51/72 Yield
Conditions & References Reaction Steps: 2
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1: 83 percent / aq. Na2CO3 / tetrahydrofuran / 14 h / Heating 2: 9 percent / t-BuOK / tetrahydrofuran / 3 h / -78 °C With potassium tert-butylate, sodium carbonate in tetrahydrofuran, 2: Dieckmann cyclization Pinto, Americo C.; Abdala, Rodrigo V.; Costa, Paulo R.R.; Tetrahedron Asymmetry; vol. 11; nb. 21; (2000); p. 4239 - 4243 View in Reaxys
O
O
4-[4,4-di(allyloxycarbonyl)-3-phenylbutanoyl]benzoyl-Rink resin
H 2N
O
N
Rx-ID: 15433046 View in Reaxys 52/72 Yield
Conditions & References Reaction Steps: 3 1: 90 percent / 48 h / -30 °C 2: 86 percent / aq. Na2CO3 / tetrahydrofuran / 14 h / Heating 3: 13 percent / t-BuOK / tetrahydrofuran / 3 h / -78 °C With potassium tert-butylate, sodium carbonate in tetrahydrofuran, 3: Dieckmann cyclization Pinto, Americo C.; Abdala, Rodrigo V.; Costa, Paulo R.R.; Tetrahedron Asymmetry; vol. 11; nb. 21; (2000); p. 4239 - 4243 View in Reaxys
O
O
4-[4,4-di(allyloxycarbonyl)-3-phenylbutanoyl]benzoyl-Rink resin
H 2N
O
N
Rx-ID: 15433048 View in Reaxys 53/72 Yield
Conditions & References Reaction Steps: 3 1: 90 percent / 48 h / -30 °C 2: 83 percent / aq. Na2CO3 / tetrahydrofuran / 14 h / Heating 3: 9 percent / t-BuOK / tetrahydrofuran / 3 h / -78 °C With potassium tert-butylate, sodium carbonate in tetrahydrofuran, 3: Dieckmann cyclization Pinto, Americo C.; Abdala, Rodrigo V.; Costa, Paulo R.R.; Tetrahedron Asymmetry; vol. 11; nb. 21; (2000); p. 4239 - 4243 View in Reaxys
O O O
N H
O
O
O
O N O
Rx-ID: 17985232 View in Reaxys 54/72 Yield
Conditions & References Reaction Steps: 2 1: 98 percent / Et3N / CH2Cl2 / 3 h 2: t-BuOK / toluene / 1.) ice-water cooling, 1 h, 2.) room temp., 1 h With potassium tert-butylate, triethylamine in dichloromethane, toluene Sunagawa; Matsumura; Sumita; Nouda; Journal of Antibiotics; vol. 48; nb. 5; (1995); p. 408 - 416
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View in Reaxys O
O O
O
2
H
N H
OH 2H
O
O
2H
N O
2H
O
Rx-ID: 39077747 View in Reaxys 55/72 Yield
Conditions & References Reaction Steps: 3 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 4 h / |Inert atmosphere 1.2: |Inert atmosphere 2.1: triethylamine; 3-carbonxybenzenesulfonyl azide / acetonitrile / 1 h / |Inert atmosphere 3.1: dirhodium tetraacetate / toluene / 4 h / 100 °C With dirhodium tetraacetate, 3-carbonxybenzenesulfonyl azide, triethylamine, 1,1'-carbonyldiimidazole in tetrahydrofuran, toluene, acetonitrile Azimioara, Mihai; Alper, Phil; Cow, Christopher; Mutnick, Daniel; Nikulin, Victor; Lelais, Gerald; Mecom, John; McNeill, Matthew; Michellys, Pierre-Yves; Wang, Zhiliang; Reding, Esther; Paliotti, Michael; Li, Jing; Bao, Dingjiu; Zoll, Jocelyn; Kim, Young; Zimmerman, Matthew; Groessl, Todd; Tuntland, Tove; Joseph, Sean B.; McNamara, Peter; Seidel, H. Martin; Epple, Robert; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 23; (2014); p. 5478 - 5483 View in Reaxys O O O
O
2
H
N H
O 2H
O
O
2H
N O
2H
O
Rx-ID: 39077757 View in Reaxys 56/72 Yield
Conditions & References Reaction Steps: 2 1: triethylamine; 3-carboxybenzenesulfonyl azide / acetonitrile / 1 h / |Inert atmosphere 2: dirhodium tetraacetate / toluene / 4 h / 100 °C With dirhodium tetraacetate, 3-carboxybenzenesulfonyl azide, triethylamine in toluene, acetonitrile Azimioara, Mihai; Alper, Phil; Cow, Christopher; Mutnick, Daniel; Nikulin, Victor; Lelais, Gerald; Mecom, John; McNeill, Matthew; Michellys, Pierre-Yves; Wang, Zhiliang; Reding, Esther; Paliotti, Michael; Li, Jing; Bao, Dingjiu; Zoll, Jocelyn; Kim, Young; Zimmerman, Matthew; Groessl, Todd; Tuntland, Tove; Joseph, Sean B.; McNamara, Peter; Seidel, H. Martin; Epple, Robert; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 23; (2014); p. 5478 - 5483 View in Reaxys
O
O O
O
O
N
N
O
O N
O O HN O
O O
O
Rx-ID: 40536778 View in Reaxys 57/72 Yield
Conditions & References Reaction Steps: 2 1.1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C
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2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.17 h / 0 °C 2.2: 12.33 h / 0 - 20 °C With dmap, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride, trifluoroacetic acid in tetrahydrofuran, dichloromethane Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
O
O
O
O
N
O
O N
O
N
O
O HN
O O
O
O
Rx-ID: 40536779 View in Reaxys 58/72 Yield
Conditions & References Reaction Steps: 2 1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 2: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 10.17 h / 0 - 20 °C With N-ethyl-N,N-diisopropylamine, trifluoroacetic acid, N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1yl-methylene]-N-methylmethanaminium hexafluorophosphate in dichloromethane, N,N-dimethyl-formamide Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
O
O O N
O
O
N
O
O
O N
O HN O
O O
O
Rx-ID: 40536780 View in Reaxys 59/72 Yield
Conditions & References Reaction Steps: 2 1.1: trifluoroacetic acid / dichloromethane / 4 h / 0 - 20 °C 2.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / tetrahydrofuran / 0.17 h / 0 °C 2.2: 12.33 h / 0 - 20 °C With dmap, 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride, trifluoroacetic acid in tetrahydrofuran, dichloromethane Das, Sukant K.; Bhatt, Nilay; Mujahid, Mohammad; Arvidsson, Per I.; Kruger, Hendrik G.; Naicker, Tricia; Govender, Thavendran; Tetrahedron Letters; vol. 56; nb. 37; (2015); p. 5172 - 5174 View in Reaxys
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O
O
O O
O
N O
NH
O
O N N
Rx-ID: 44058648 View in Reaxys 60/72 Yield
Conditions & References Reaction Steps: 3 1.1: isopropylmagnesium chloride / tetrahydrofuran / 3 h / 0 - 40 °C 1.2: 4 h / 0 - 20 °C 2.1: m-carboxybenzenesulfonyl azide; triethylamine / acetonitrile / 2 h / 20 °C / |Inert atmosphere 3.1: dirhodium tetraacetate / toluene / 1 h / 90 °C / |Inert atmosphere With dirhodium tetraacetate, m-carboxybenzenesulfonyl azide, isopropylmagnesium chloride, triethylamine in tetrahydrofuran, toluene, acetonitrile Doebelin, Christelle; He, Yuanjun; Kamenecka, Theodore M.; Tetrahedron Letters; vol. 57; nb. 50; (2016); p. 5658 - 5660 View in Reaxys
O
O
O O O
N H
O
O
N O O
Rx-ID: 15586755 View in Reaxys 61/72 Yield
Conditions & References Reaction Steps: 2 1: 80 percent / acetonitrile / 1 h / 0 °C 2: t-BuOK / toluene / 0.5 h / 0 °C With potassium tert-butylate in toluene, acetonitrile, 1: Condensation / 2: Dickemann cyclization St-Denis; Tak Hang Chan; Canadian Journal of Chemistry; vol. 78; nb. 6; (2000); p. 776 - 783 View in Reaxys
O
O
O O
O N
Cl
O O
Rx-ID: 15597322 View in Reaxys 62/72 Yield
Conditions & References Reaction Steps: 2 1: 80 percent / acetonitrile / 1 h / 0 °C 2: t-BuOK / toluene / 0.5 h / 0 °C With potassium tert-butylate in toluene, acetonitrile, 1: Condensation / 2: Dickemann cyclization St-Denis; Tak Hang Chan; Canadian Journal of Chemistry; vol. 78; nb. 6; (2000); p. 776 - 783 View in Reaxys
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O H N
O
O O
O
N
O
O
Rx-ID: 18871712 View in Reaxys 63/72 Yield
Conditions & References Reaction Steps: 2 1: 71 percent / Na2CO3 / 5 h / 120 °C 2: 65 percent / 50percent NaH/oil / toluene / 14 h / 25 °C With sodium hydride, sodium carbonate, oil in toluene McHugh, Michael; Proctor, George R.; Journal of Chemical Research, Miniprint; nb. 8; (1984); p. 2230 - 2253 View in Reaxys O
O
NH 2
O O N
O
Rx-ID: 18873593 View in Reaxys 64/72 Yield
Conditions & References Reaction Steps: 3 1: 59 percent / SnCl4 / benzene / 40 h / Heating 2: 71 percent / Na2CO3 / 5 h / 120 °C 3: 65 percent / 50percent NaH/oil / toluene / 14 h / 25 °C With tin(IV) chloride, sodium hydride, sodium carbonate, oil in toluene, benzene McHugh, Michael; Proctor, George R.; Journal of Chemical Research, Miniprint; nb. 8; (1984); p. 2230 - 2253 View in Reaxys
O
O O N
Cl
Rx-ID: 37042866 View in Reaxys 65/72 Yield
Conditions & References Reaction Steps: 2 1.1: thionyl chloride / methanol / 24 h / 0 - 20 °C 1.2: 0 - 20 °C 2.1: 4-methylmorpholine N-oxide; TPAP / dichloromethane / 0.5 h With thionyl chloride, TPAP, 4-methylmorpholine N-oxide in methanol, dichloromethane Patent; GILEAD SCIENCES, INC.; BJORNSON, Kyla; CANALES, Eda; COTTELL, Jeromy, J.; KARKI, Kapil, Kumar; KATANA, Ashley, Anne; KATO, Darryl; KOBAYASHI, Tetsuya; LINK, John, O.; MARTINEZ, Ruben; PHILLIPS, Barton, W.; PYUN, Hyung-jung; SANGI, Michael; SCHRIER, Adam, James; SIEGEL, Dustin; TAYLOR, James, G.; TRAN, Chinh, Viet; TREJO MARTIN, Teresa, Alejandra; VIVIAN, Randall, W.; YANG, ZhengYu; ZABLOCKI, Jeff; ZIPFEL, Sheila; WO2014/8285; (2014); (A1) English View in Reaxys
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O
O
O
O
O
N O
O
HO
O
Rx-ID: 42407922 View in Reaxys 66/72 Yield
Conditions & References Reaction Steps: 3 1.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 18 h / 25 °C 1.2: 5.5 h / 0 - 40 °C 2.1: 3-carbonxybenzenesulfonyl azide; triethylamine / acetonitrile / 2 h / 25 °C / |Inert atmosphere 3.1: dirhodium tetraacetate / toluene / 1 h / 90 °C / |Inert atmosphere With dirhodium tetraacetate, 3-carbonxybenzenesulfonyl azide, triethylamine, 1,1'-carbonyldiimidazole in tetrahydrofuran, toluene, acetonitrile Patent; EOLAS THERAPEUTICS, INC.; KAMENECKA, Theodore M.; HE, Yuanjun; (105 pag.); WO2016/25669; (2016); (A1) English View in Reaxys
O O
O
O
N O
O
N O
O
O
Rx-ID: 9038882 View in Reaxys 67/72 Yield
Conditions & References
45 %
Dieckman-type cyclization Pellegrini, Nadia; Schmitt, Martine; Guery, Sebastien; Bourguignon, Jean-Jacques; Tetrahedron Letters; vol. 43; nb. 17; (2002); p. 3243 - 3246 View in Reaxys O
OH O NH
Rx-ID: 37325341 View in Reaxys 68/72 Yield
Conditions & References Accordingly, the appended claims are intended to encompass all such modifications and changes as fall within the true spirit and scope of this invention. 1. A method of improving health in a canine, comprising: providing a nutritional supplement, comprising: L-arginine; oxo-proline; and L-lysine; and Patent; Basic Research L.L.C.; HEATON, Amy L.; Friedlander, Mitchell K.; Gay, Dennis; US2014/79825; (2014); (A1) English View in Reaxys
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O
O O N O O
Rx-ID: 5494592 View in Reaxys 69/72 Yield
Conditions & References 1-Ethoxycarbonyl-3-hydroxy-pyrrolidin-2-carbonsaeure-ethylester, Chrom(VI)-oxid, Acn., wss. H2SO4 Blake et al.; Journal of the American Chemical Society; vol. 86; (1964); p. 5293,5298 View in Reaxys aus 1-Ethoxycarbonyl-2-cyano-pyrrolidin-3-on (Uchibayashi, J. pharn. Soc. Japan 78 <1958> 845) nur in geringer Menge bei der Ethanolyse Blake et al.; Journal of the American Chemical Society; vol. 86; (1964); p. 5293,5298 View in Reaxys O
O O N O O
Rx-ID: 8331632 View in Reaxys 70/72 Yield
Conditions & References N-Benzyloxycarbonyl-trans-3-hydroxy-DL-prolinmethylester, CrO3, Acn., H2SO4 (65min, R.T.) Irreverre et al.; Journal of the American Chemical Society; vol. 85; (1963); p. 2824,2830 View in Reaxys (yield)93percent Irreverre et al.; Journal of the American Chemical Society; vol. 85; (1963); p. 2824,2830 View in Reaxys
O
O 14
C O
N O O
Rx-ID: 5627001 View in Reaxys 71/72 Yield
Conditions & References N-Ethoxycarbonyl-N-(2-ethoxycarbonylethyl)-(1-14C)glycin-ethylester, K-tert.-butanolat, Toluol (0grad; neben 1Ethoxycarbonyl-4-oxo-(4-14C)pyrrolidin-3-carbonsaeure-ethylester) Blake et al.; Journal of the American Chemical Society; vol. 86; (1964); p. 5293,5298 View in Reaxys
O
O O N O O
Rx-ID: 5635321 View in Reaxys 72/72
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Yield
Conditions & References Glycinester 2, K-tert.-butylat Feil,P.D.; Vercellotti,J.R.; Carbohydrate Research; vol. 31; (1973); p. 311 - 322 View in Reaxys
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