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

Participants

Reaction Steps

44 g (210.58 mmol) of 2,6-dichloro-5-fluoronicotinamide was added at RT to a suspension of 21.9 g (335.35 mmol) of zinc in methanol (207 ml). Then acetic acid (18.5 ml) was added and it was heated under reflux for 24 h, with stirring. Then the flask contents were decanted from the zinc and ethyl acetate (414 ml) and saturated aqueous sodium hydrogen carbonate solution (414 ml) were added and stirred vigorously. Then it was filtered with suction on diatomaceous earth and washed again three times with ethyl acetate (517 ml each time). The organic phase was separated and the aqueous phase was washed with ethyl acetate (258 ml). The combined organic phases were washed once with saturated aqueous sodium hydrogen carbonate solution (414 ml), dried and concentrated by vacuum evaporation. Dichloromethane (388 ml) was added to the crystals thus obtained, and left to precipitate for 20 min. It was filtered with suction again and washed with diethyl ether and suction-dried.

Provenance & Evidence