Lithium Hydroxide → rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid

HRID 909097ノート

反応式

HRID 909097 の反応式
C([O:3][C:4](=[O:35])[CH2:5][CH2:6][N:7]1[CH2:11][C@@H:10]([CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C@@:9]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[F:26])([C:17]#[N:18])[C@H:8]1[C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=1[F:34])C.[Li+].[OH-]>C1COCC1.O>[Cl:33][C:29]1[C:28]([F:34])=[C:27]([C@@H:8]2[C@:9]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=3[F:26])([C:17]#[N:18])[C@H:10]([CH2:12][C:13]([CH3:15])([CH3:16])[CH3:14])[CH2:11][N:7]2[CH2:6][CH2:5][C:4]([OH:35])=[O:3])[CH:32]=[CH:31][CH:30]=1

参加物

5

反応物 2

HCID 3939Lithium HydroxideHCID 67095542rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid ethyl ester

生成物 1

HCID 51357804rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid収率 100%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid ethyl ester (12.3 mg, 0.0235 mmol) in THF (2 mL) was added a solution of LiOH (Aldrich, 6.7 mg, 0.16 mmol) in water (1 mL) and the reaction mixture was stirred at rt for 22 hrs. The reaction mixture was partly concentrated and quenched with 1 N HCl (pH 6-7), extracted with EtOAc, washed with water (2×), and saturated NaCl. The organic phase was separated, and dried over Na2SO4. The mixture was then concentrated to give rac-3-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-propionic acid (11 mg, 100%). HRMS (ES+) m/z Calcd for C25H26Cl2F2N2O2+H [(M+H)+]: 495.1412; Found: 495.1413.

後処理

  1. concentrationThe reaction mixture was partly concentrated
  2. customquenched with 1 N HCl (pH 6-7)
  3. extractionextracted with EtOAc
  4. washwashed with water (2×), and saturated NaCl
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. concentrationThe mixture was then concentrated

出典と根拠

ORDレコード
ord-5adf8c1227e44547b74c721185b5340c
出典データセット
uspto-grants-2011_09
特許番号
US08017607B2

反応ノート

読み込み中…