Hydrochloric Acid → rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid

HRID 909054ノート

反応式

HRID 909054 の反応式
C[O:2][C:3](=[O:42])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:41])[CH2:12][N:13]2[CH2:17][C@H:16]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:19]=3[F:25])[C@:15]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=3[F:35])([C:26]#[N:27])[C@@H:14]2[CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:6][CH:5]=1.[OH-].[Na+].CO.Cl>O1CCCC1>[Cl:24][C:20]1[C:19]([F:25])=[C:18]([C@H:16]2[CH2:17][N:13]([CH2:12][C:11]([NH:10][C:7]3[CH:6]=[CH:5][C:4]([C:3]([OH:42])=[O:2])=[CH:9][CH:8]=3)=[O:41])[C@@H:14]([CH2:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C@@:15]2([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=2[F:35])[C:26]#[N:27])[CH:23]=[CH:22][CH:21]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 51355304rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid methyl ester

生成物 1

HCID 51355305rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid収率 96.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid methyl ester (0.35 g, 0.57 mmol) in tetrahydrofuran (30 mL) was added an aqueous solution (1 N) of NaOH (10 mL, 10 mmol) and methanol (10 mL). The reaction mixture was stirred at room temperature for 24 h, and the “pH” of the solution was adjusted to 5-6 by aqueous HCl solution. The mixture was extracted ethyl acetate twice. The combined organic extracts were washed with water, brine, dried over MgSO4, and concentrated to give rac-4-{2-[(2S,3R,4S)-4-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-2-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetylamino}-benzoic acid as a white solid (0.33 g, 96%). HRMS (ES+) m/z Calcd for C31H29Cl2F2N3O3+H [(M+H): 600.1267; Found: 600.1628.

後処理

  1. extractionThe mixture was extracted ethyl acetate twice
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-9d4c82063bd044698923fc8eca10acf5
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…