Acetic Acid → 2-Chloro-5-fluoropyridine-3-carboxamide

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Reaction Steps

At RT, 44 g (210.58 mmol) of 2,6-dichloro-5-fluoronicotinamide were added to a suspension of 21.9 g (335.35 mmol) of zinc in methanol (207 ml). Acetic acid (18.5 ml) was then added, and the mixture was heated at reflux with stirring for 24 h. The contents of the flask were then decanted from the zinc, ethyl acetate (414 ml) and saturated aqueous sodium bicarbonate solution (414 ml) were added and the mixture was stirred vigorously. The mixture was then filtered off with suction through kieselguhr and washed three times with ethyl acetate (517 ml each). The organic phase was separated off and the aqueous phase was washed with ethyl acetate (258 ml). The combined organic phases were washed once with saturated aqueous sodium bicarbonate solution (414 ml), dried and concentrated under reduced pressure. Dichloromethane (388 ml) was added to the crystals obtained in this manner, and the crystals were triturated for 20 min. The crystals were once more filtered off with suction and washed with diethyl ether and sucked dry.

Provenance & Evidence