(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: acetic acid / dichloromethane / 2 h / 20 °C 2: 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; sodium hypochlorite; sodium bromide; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C View Scheme
参考文献
ZHEJIANG HISOAR PHARMACEUTICAL CO., LTD.; Pan, Xianhua; Li, Weijin; Zhang, Qunhui; Ruan, Libo; Yu, Wansheng; Deng, Fei; Ma, Tianhua; Huang, Mingwang; He, Minhuan
Patent: US2013/281695 A1, 2013 ;
反应条件
1: palladium 10 on activated carbon; hydrogen / 12 h / 4560.31 Torr 2: 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; sodium hypochlorite; sodium bromide; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C View Scheme
参考文献
ZHEJIANG HISOAR PHARMACEUTICAL CO., LTD.; Pan, Xianhua; Li, Weijin; Zhang, Qunhui; Ruan, Libo; Yu, Wansheng; Deng, Fei; Ma, Tianhua; Huang, Mingwang; He, Minhuan
Patent: US2013/281695 A1, 2013 ;
反应条件
1.1: hydrogen; 20 palladium(II) hydroxide on carbon / methanol / 12 h / 50 °C / 4560.31 Torr / |Autoclave 1.2: 8 h / 20 °C 2.1: 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; sodium hypochlorite; sodium bromide; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C View Scheme
参考文献
ZHEJIANG HISOAR PHARMACEUTICAL CO., LTD.; Pan, Xianhua; Li, Weijin; Zhang, Qunhui; Ruan, Libo; Yu, Wansheng; Deng, Fei; Ma, Tianhua; Huang, Mingwang; He, Minhuan
Patent: US2013/281695 A1, 2013 ;
反应条件
1.1: sodium tetrahydroborate; iodine / tetrahydrofuran; methanol / 2 h / 0 - 5 °C / |Reflux 2.1: triethylamine / dichloromethane / 4 h / 0 - 20 °C 3.1: n-butyllithium / tetrahydrofuran / 0.5 h / -10 °C / |Inert atmosphere 4.1: tert-butylmagnesium bromide; copper(I) bromide dimethylsulfide complex / tetrahydrofuran / 0.25 h / -20 - -5 °C / |Inert atmosphere 4.2: 0.08 h 5.1: methyl iodide; water / methanol / 0.5 h / 20 °C / |Cooling with ice 6.1: 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; sodium hypochlorite; sodium bromide; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C View Scheme
参考文献
ZHEJIANG HISOAR PHARMACEUTICAL CO., LTD.; Pan, Xianhua; Li, Weijin; Zhang, Qunhui; Ruan, Libo; Yu, Wansheng; Deng, Fei; Ma, Tianhua; Huang, Mingwang; He, Minhuan
Patent: US2013/281695 A1, 2013 ;
反应条件
1.1: triethylamine / dichloromethane / 4 h / 0 - 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -10 °C / |Inert atmosphere 3.1: tert-butylmagnesium bromide; copper(I) bromide dimethylsulfide complex / tetrahydrofuran / 0.25 h / -20 - -5 °C / |Inert atmosphere 3.2: 0.08 h 4.1: methyl iodide; water / methanol / 0.5 h / 20 °C / |Cooling with ice 5.1: 2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; sodium hypochlorite; sodium bromide; sodium hydrogencarbonate / dichloromethane / 2 h / 0 °C View Scheme
参考文献
ZHEJIANG HISOAR PHARMACEUTICAL CO., LTD.; Pan, Xianhua; Li, Weijin; Zhang, Qunhui; Ruan, Libo; Yu, Wansheng; Deng, Fei; Ma, Tianhua; Huang, Mingwang; He, Minhuan
Patent: US2013/281695 A1, 2013 ;
反应条件
1: (+)-cinchonine / acetone / Resolution of racemate; Reflux 2: triethylamine; diphenyl phosphoryl azide / toluene / 5.5 h / 80 °C / Inert atmosphere; Reflux 3: water; lithium hydroxide hydrate / methanol / 24 h / 20 °C View Scheme
参考文献
Chemo Ibérica, S.A.
Patent: EP2423178 A1, 2012 ;
反应条件
1: triethylamine; diphenyl phosphoryl azide / toluene / 5.5 h / 80 °C / Inert atmosphere; Reflux 2: water; lithium hydroxide hydrate / methanol / 24 h / 20 °C View Scheme
参考文献
Chemo Ibérica, S.A.
Patent: EP2423178 A1, 2012 ;
反应条件
1.1: sodium iodide; sodium azide / N,N-dimethyl-formamide / 16 h / 70 °C / Inert atmosphere 2.1: triphenylphosphine / acetonitrile / 13.5 h / 20 - 70 °C 2.2: 2 h 3.1: 18-crown-6 ether; ammonium chloride / dimethyl sulfoxide / 2 h / 80 °C 4.1: potassium hydroxide / ethanol; water / 12 h / 80 °C 4.2: 20 °C View Scheme
参考文献
DONG-A PHARMACEUTICAL. CO., LTD
Patent: US2012/16125 A1, 2012 ;
US 20120016125 A1
反应条件
1.1: 18-crown-6 ether; ammonium chloride / dimethyl sulfoxide / 2 h / 80 °C 2.1: potassium hydroxide / ethanol; water / 12 h / 80 °C 2.2: 20 °C View Scheme
参考文献
DONG-A PHARMACEUTICAL. CO., LTD
Patent: US2012/16125 A1, 2012 ;
US 20120016125 A1
反应条件
1.1: triphenylphosphine / acetonitrile / 13.5 h / 20 - 70 °C 1.2: 2 h 2.1: 18-crown-6 ether; ammonium chloride / dimethyl sulfoxide / 2 h / 80 °C 3.1: potassium hydroxide / ethanol; water / 12 h / 80 °C 3.2: 20 °C View Scheme
参考文献
DONG-A PHARMACEUTICAL. CO., LTD
Patent: US2012/16125 A1, 2012 ;
US 20120016125 A1
