4-(Trifluoromethoxy)fluorobenzene

Uses

Synthesis

338792-64-6

352-67-0

The general procedure for the synthesis of p-fluorotrifluoromethoxybenzene from 2,2-difluoro-2-(4-fluorophenoxy)acetic acid was as follows: a stir bar was added to a 5 mL microwave vial in an argon-protected glove box and sealed. Selectfluor (177.1 mg, 0.5 mmol, 2.0 eq.), silver trifluoromethanesulfonate (12.8 mg, 0.05 mmol, 20 mol%), and 2,2-difluoro-2-(4-fluorophenoxy)acetic acid (0.25 mmol, 1.0 eq.) were added sequentially. The vial was charged with dichloromethane (1.8 mL), trifluoroacetic acid (76.5 μL, 1.0 mmol, 4.0 equiv) and water (0.2 mL). The reaction mixture was heated at 55 °C for 1 hour. After completion of the reaction, the mixture was cooled to room temperature, diluted with dichloromethane (4 mL), washed sequentially with water (3 x 5 mL) and brine (5 mL), dried over anhydrous magnesium sulfate and filtered. The dried organic phase was concentrated on a rotary evaporator. The crude product obtained was dissolved in a small amount of dichloromethane and purified by passing through a silica gel column (10 g, Biotage), first dried with air and then eluted with pentane. The fractions containing the pure product were combined and the solvent evaporated to give pure p-fluorotrifluoromethoxybenzene.

References