Dimethylformamide → 4-Bromo-2,6-difluorobenzaldehyde

Participants

Reaction Steps

To a solution of diisopropylamine (93 mL, 0.66 mol) in dry tetrahydrofuran (300 mL) at −50° C. was added n-BuLi (212 mL of 2.M in hexanes, 0.53 mol.) dropwise. The solution was stirred at room temperature for 30 mins. This solution was then added dropwise to a cooled (−75° C.) solution of 1-bromo-3,5-difluorobenzene (84 g, 0.44 mol) in dry tetrahydrofuran (900 mL). The mixture was stirred at −78° C. for one hour. Dry dimethylformamide (63.6 mL, 0.82 mol) was added and the mixture was stirred for two hours. The cooling bath was removed and the mixture was slowly warmed to room temperature. The mixture was diluted with diethyl ether and poured into cooled 1 M aqueous hydrochloric acid (1 L). The aqueous phase was extracted with diethyl ether. The combined phases were dried, filtered, and the solvent was removed in vacuo to give the crude product. The crude was re-crystallized with ethyl acetate and petroleum ether to afford the title compound.

Provenance & Evidence