Dimethylformamide → 2-Chloro-6,8-difluoroquinoline

Participants

Reaction Conditions

Reaction Steps

6,8-Difluoroquinolin-2-ol (9.89 g, 54.6 mmol) was slurried in 1,2-dichloroethane (550 mL) and treated with DMF (1 mL), and then 2M oxalyl chloride in CH2Cl2 (81.9 mL, 164 mmol) was added dropwise. The reaction was heated to 70° C. for 1 hour and then cooled and concentrated in vacuo. The residue was dissolved in CHCl3 and washed with 50% saturated NaHCO3. The aqueous layer (pH 8) was washed twice with CHCl3 and the combined organics were dried over Na2SO4 and charcoal, filtered, and concentrated in vacuo to a brown solid. The solid was purified by recrystallization from hot hexanes and 1,2-dichloroethane (minimum volume). The solid was collected, washed with hexanes and air-dried to provide the desired product as an off-white solid (5.78 g).

Provenance & Evidence