Acetyl chloride → 1-(5-Chloro-4-fluoro-2-hydroxyphenyl)ethanone
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[C:10](Cl)(=[O:12])[CH3:11].[Cl-].[Cl-].[Cl-].[Al+3]>>[Cl:1][C:2]1[C:3]([F:9])=[CH:4][C:5]([OH:8])=[C:6]([C:10](=[O:12])[CH3:11])[CH:7]=1Participants
4
Conditions
- Temperature
- 60 °C
Procedure
To 4-chloro-3-fluorophenol (from Aldrich, 20 g, 100 mmol) was added acetyl chloride (14.1 mL, 199 mmol) under N2 with stirring. The resulting mixture turned into a clear solution at room temperature quickly and it was heated at 60° C. for 2 hours. To the resultant mixture was added aluminum trichloride (25.0 g, 187 mmol) in portions and the reaction mixture was heated at 180° C. for 30 minutes. The solids slowly dissolved at high temperature. The reaction mixture was then cooled to room temperature while the flask was swirled carefully in order for the solid to form a thin layer inside the flask and then slowly quenched with 1.0 N HCl (300 mL) while cooling in an ice-bath and stirred overnight. The yellow precipitate was washed with water and dried under vacuum to give the desired product as a yellow solid (23.8 g), which was directly used in the next step without further purification.