Dimethylformamide → 2-Chloro-6,7-difluoroquinoline-3-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

Phosphoryl chloride (147.1 mL) is carefully added to DMF (32.5 mL) at 0-15° C. to prepare a solution of vilsmeier reagent in phosphoryl chloride, and the mixture is warmed to 30° C. to give clear pale yellow mixture. 3,4-difluoroacetanilide (30 g, 0.12 mol) is added to the mixture, and the resulting mixture is stirred at 80° C. for 30 min, 90° C. for 30 min, 100° C. for 18 hours, and finally 120° C. for 2 hours. The mixture is cooled to room temperature, poured onto ice-water (1500 mL) and extracted with CH2Cl2 7 times (total 3000 mL). The combined organic layer is dried over magnesium sulfate, filtered and concentrated. The brown crystal is collected and washed with CH2Cl2 to give 2-chloro-6,7-difluoroquinoline-3-carbaldehyde as a pale yellow powder.

Provenance & Evidence