(3R)-N-叔丁氧羰基-3-氨基-4-(2,4,5-三氟苯基)丁酸合成路线 （共 62 条）
反应条件
1: in tetrahydrofuran; water T=25 - 30°C; 6 h; 2: With sodium hydrogen sulphate pH=2;
参考文献
Mylan India Private Limited
Patent: US2012/108598 A1, 2012 ;
Location in patent: Page/Page column 10 ;
反应条件
1: 95 percent / N,N-dimethylaminopyridine; N,N-diisopropylethylamine; trimethylacetylchloride / acetonitrile / 3 h / 45 °C 2: 88.7 percent / toluene / 3 h / Heating 3: 95 percent / ammonium acetate / methanol / 7 h / Heating 4: 68 percent / H2; (R) chiral ferrocenyl derivative / chloro(1,5-cyclooctadiene)rhodium(I) dimer / 2,2,2-trifluoro-ethanol / 40 h / 50 °C / 5171.62 Torr 5: 93 percent / CH2Cl2 / 3 h / 20 °C 6: 99 percent / aq. LiOH / tetrahydrofuran; methanol / 3 h / 20 °C View Scheme
参考文献
Jiangsu Hengrui Medicine Co., Ltd.
Patent: US2011/130587 A1, 2011 ;
反应条件
1.1: isopropylmagnesium chloride / tetrahydrofuran / 2 h / -15 - 20 °C / Inert atmosphere 2.1: copper(l) iodide / tetrahydrofuran / 3 h / -20 - -15 °C / Inert atmosphere 3.1: sodium iodide; sodium azide / N,N-dimethyl-formamide / 16 h / 70 °C / Inert atmosphere 4.1: triphenylphosphine / acetonitrile / 13.5 h / 20 - 70 °C 4.2: 2 h 5.1: 18-crown-6 ether; ammonium chloride / dimethyl sulfoxide / 2 h / 80 °C 6.1: potassium hydroxide / ethanol; water / 12 h / 80 °C 6.2: 20 °C View Scheme
参考文献
Zhejiang Jiuzhou Pharmaceutical Co., Ltd.
Patent: EP2481722 A1, 2012 ;
反应条件
1.1: ethanol / 3 h / 70 °C 2.1: formic acid / ethanol / 3 h / Reflux 2.2: 2 h / 40 °C / Reflux 3.1: methanol / Reflux 4.1: sodium carbonate / water; methanol / 3 h / 30 °C / pH 10 5.1: sodium hydroxide; water / methanol / 2 h / 40 - 45 °C 5.2: pH 3 / Acidic conditions View Scheme
参考文献
Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co. Ltd.
Patent: EP2404921 A1, 2012 ;
反应条件
1.1: formic acid / ethanol / 3 h / Reflux 1.2: 2 h / 40 °C / Reflux 2.1: methanol / Reflux 3.1: sodium carbonate / water; methanol / 3 h / 30 °C / pH 10 4.1: sodium hydroxide; water / methanol / 2 h / 40 - 45 °C 4.2: pH 3 / Acidic conditions View Scheme
参考文献
Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co. Ltd.
Patent: EP2404921 A1, 2012 ;
反应条件
1: 95 percent / ammonium acetate / methanol / 7 h / Heating 2: 68 percent / H2; (R) chiral ferrocenyl derivative / chloro(1,5-cyclooctadiene)rhodium(I) dimer / 2,2,2-trifluoro-ethanol / 40 h / 50 °C / 5171.62 Torr 3: 93 percent / CH2Cl2 / 3 h / 20 °C 4: 99 percent / aq. LiOH / tetrahydrofuran; methanol / 3 h / 20 °C View Scheme
参考文献
Mylan India Private Limited
Patent: US2012/108598 A1, 2012 ;
反应条件
1: 88.7 percent / toluene / 3 h / Heating 2: 95 percent / ammonium acetate / methanol / 7 h / Heating 3: 68 percent / H2; (R) chiral ferrocenyl derivative / chloro(1,5-cyclooctadiene)rhodium(I) dimer / 2,2,2-trifluoro-ethanol / 40 h / 50 °C / 5171.62 Torr 4: 93 percent / CH2Cl2 / 3 h / 20 °C 5: 99 percent / aq. LiOH / tetrahydrofuran; methanol / 3 h / 20 °C View Scheme
参考文献
Mylan India Private Limited
Patent: US2012/108598 A1, 2012 ;
反应条件
1.1: hydrogen / [RhCl(η2:η2-cycloocta-1,5-diene)]2; (R)-1-[(S)-2-(diphenyl phosphino)ferrocenyl]-ethyl-tert-butylphosphine / water; methanol / 24 h / 30 °C / 5069.54 Torr 2.1: sodium hydroxide; water / methanol / 1.5 h / 40 - 45 °C 2.2: pH 2 - 3 View Scheme
参考文献
SHANGHAI HENGRUI PHARMACEUTICAL CO., LTD.; JIANGSU HENGRUI MEDICINE CO., LTD.
Patent: US2012/65209 A1, 2012 ;
反应条件
1.1: hydrogen / 5 palladium on charcoal / methanol / 4 h / 40 °C / 3750.38 Torr / Autoclave; Inert atmosphere 2.1: sodium hydroxide; water / toluene / 3 h / 60 °C 2.2: 2 h / 20 - 30 °C View Scheme
参考文献
Zhejiang Jiuzhou Pharmaceutical Co., Ltd.
Patent: EP2481722 A1, 2012 ;
反应条件
1.1: iodine; magnesium / tetrahydrofuran / 3 h / 30 - 40 °C 1.2: -20 - 20 °C 2.1: hydrogen / 5 palladium on charcoal / methanol / 4 h / 40 °C / 3750.38 Torr / Autoclave; Inert atmosphere 3.1: sodium hydroxide; water / toluene / 3 h / 60 °C 3.2: 2 h / 20 - 30 °C View Scheme
参考文献
Zhejiang Jiuzhou Pharmaceutical Co., Ltd.
Patent: EP2481722 A1, 2012 ;
