Hydrochloric Acid → 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoic acid

HRID 1807282ノート

反応式

HRID 1807282 の反応式
[Cl:1][C:2]1[C:3]([F:43])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([O:41]C)=[O:40])=[CH:33][CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.O.[OH-].[Li+].Cl>C1COCC1.O>[Cl:1][C:2]1[C:3]([F:43])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:32]=[CH:33][C:34]([CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[CH:35][CH:36]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 53357489methyl 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoate

生成物 1

HCID 533574903-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoic acid収率 100.3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of chiral methyl 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoate (58.8 mg, 0.0936 mmol) in THF (5 ml) was treated with LITHIUM HYDROXIDE MONOHYDRATE (15.7 mg, 0.374 mmol) in water (2.5 ml) and stirred at rt overnight. The mixture was then treated with 1 N HCl to pH 3-4, extracted with ethyl acetate. The organic extracts were washed with water and brine, dried over sodium sulfate and concentrated to give chiral 3-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)phenyl)propanoic acid (57.7 mg, 100%) as a white solid. MS (ES+) m/z Calcd: [(M+H)+]: 614.17. found: 614.2.

後処理

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-c21120a4ba6643c5856866fa1aae637c
出典データセット
uspto-grants-2013_01
特許番号
US08354444B2

反応ノート

読み込み中…