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 1475680Notes

Reaction equation

HRID 1475680 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-1faf731f0919462d945fd71c72249b42
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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