4-Fluorobenzoyl chloride → 2-Bromo3-chloro-5-(4-fluorobenzoyl)-thiophene

Participants

Reaction Conditions

Reaction Steps

Ferric chloride (301.2 g) was added to a stirred solution of 2-bromo-3-chlorothiophene (148.5 g) and 4-fluorobenzoyl chloride (169.7 g) in dichloromethane (2230 ml), cooled to 18° C. in an icetwater bath. The temperature of the reaction mixture rose to 22° C. and was then cooled to 12° C. Cooling was removed and the reaction mixture was stirred for a further 50 min during which time the internal temperature rose to 16° C. The reaction mixture was re-cooled to 10° C., water (700 ml) was added carefully, keeping the internal temperature below 15° C., and the mixture was then stirred for 1 h. The dichloromethane layer was separated and the aq layer was washed with dichloromethane. The combined dichloromethane layer was washed with water and saturated sodium bicarbonate solution. The dichloromethane was separated and the aq. layer filtered through dicalite and extracted with dichloromethane. The extract was washed with water, dried (Na2SO4) and evaporated to dryness to give 2-bromo-3-chloro-5-(4-fluorobenzoyl)-thiophene as a solid (233.3 g).

Provenance & Evidence