Ethyl vinyl ether → tert-Butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)(vinyloxy)methyl]cyclopropanecarboxylate

HRID 1475680ノート

反応式

HRID 1475680 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:19])[C:9]2([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:11][CH2:10]2)=[CH:4][C:3]=1[NH:20][C:21](=[O:36])[C@H:22]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[C@@H:23]([CH3:28])[C:24]([F:27])([F:26])[F:25].[CH:37](OCC)=[CH2:38]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:19][CH:37]=[CH2:38])[C:9]2([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:10][CH2:11]2)=[CH:4][C:3]=1[NH:20][C:21](=[O:36])[C@H:22]([C:29]1[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=1)[C@@H:23]([CH3:28])[C:24]([F:27])([F:25])[F:26]

参加物

4

反応物 2

HCID 8023Ethyl vinyl ether2 回HCID 68006961tert-butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)(hydroxy)methyl]cyclopropanecarboxylate

生成物 1

HCID 67957882tert-Butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)(vinyloxy)methyl]cyclopropanecarboxylate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

Under argon, 473 mg (0.87 mmol) of tert-butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)(hydroxy)methyl]cyclopropanecarboxylate (as diastereomer mixture) were dissolved in 2.4 ml of dichloromethane, and 1.24 ml (13 mmol) of ethyl vinyl ether and 11 mg (0.03 mmol) of)bis(acetato)(1,10-phenanthrolin-N1,N10)palladium [J. Org. Chem. 62, 1560-1562 (1997)] were added at room temperature. The reaction solution was then heated to 50° C. and stirred at this temperature for two days. Another 1.24 ml (13 mmol) of ethyl vinyl ether and 11 mg (0.03 mmol) of)bis(acetato)(1,10-phenanthrolin-N1,N10)palladium were then added, and stirring of the reaction mixture was continued at 50° C. overnight. This procedure was repeated two more times. The reaction solution was then cooled to room temperature and concentrated to dryness under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/dichloromethane 1:1). This gave 298 mg of the target compound (60% of theory).

後処理

  1. stirringstirring of the reaction mixture
  2. waitwas continued at 50° C. overnight
  3. temperatureThe reaction solution was then cooled to room temperature
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/dichloromethane 1:1)

出典と根拠

ORDレコード
ord-1faf731f0919462d945fd71c72249b42
出典データセット
uspto-grants-2015_04
特許番号
US09018258B2

反応ノート

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