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Cesium carbonate → 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid acetoxymethyl ester

HRID 882355
ノート
印刷プレビュー

反応式

HRID 882355 の反応式
[C:1]([O:4][CH2:5]I)(=[O:3])[CH3:2].[Cl:7][C:8]1[C:9]([F:48])=[C:10]([C@@H:14]2[C@:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[F:28])([C:19]#[N:20])[C@H:17]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[NH:16][C@H:15]2[C:34]([NH:36][C:37]2[CH:45]=[CH:44][C:40]([C:41]([OH:43])=[O:42])=[CH:39][C:38]=2[O:46][CH3:47])=[O:35])[CH:11]=[CH:12][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:4][CH2:5][O:43][C:41](=[O:42])[C:40]1[CH:44]=[CH:45][C:37]([NH:36][C:34]([C@H:15]2[C@H:14]([C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([Cl:7])[C:9]=3[F:48])[C@:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[F:28])([C:19]#[N:20])[C@H:17]([CH2:29][C:30]([CH3:32])([CH3:33])[CH3:31])[NH:16]2)=[O:35])=[C:38]([O:46][CH3:47])[CH:39]=1)(=[O:3])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 11820084Iodomethyl acetateHCID 53358942Idasanutlin

生成物 1

HCID 717388104-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid acetoxymethyl ester収率 19.1%

試薬・触媒・溶媒 2

HCID 6228
Dimethylformamide
溶媒
HCID 8857Ethyl Acetate溶媒

実験手順

A portion of this iodomethyl acetate (661 mg, 3.31 mmol) was added to a suspension of chiral 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (200.1 mg, 0.325 mmol) and cesium carbonate (964.4 mg, 2.93 mmol) in dimethylformamide (8 mL) and the reaction was stirred in the dark overnight. It was then taken up in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography (hexane/ethyl acetate, 80/20 to 10/90) to give chiral-4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid acetoxymethyl ester as a white solid (42.8 mg, 19% yield). MS (ES+) m/z calcd. for C34H34Cl2F2N3O6: [(M+H)+]: 688, found: 688

後処理

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (hexane/ethyl acetate, 80/20 to 10/90)

出典と根拠

ORDレコード
ord-b68745d85fa244a6955527173608cb19
出典データセット
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08993614B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート