Isonicotinic Acid → Pyridine-4-carbonyl chloride

Participants

Reaction Steps

Thionyl chloride (10 mL) was added to isonicotinic acid (370 mg, 3 mmol) and the mixture was stirred at reflux for 6 hr. Thionyl chloride was evaporated under reduced pressure and the residues was dried in vacuum to give isonicotinoyl chloride. Methyl 2-amino-3-hydroxybenzoate (167 mg, 1.0 mmol) and pyridine (240 mg, 3.0 mmol) were added to toluene (10 mL) and the mixture was stirred at room temperature for 30 min. isonicotinoyl chloride (420 mg, 3.0 mmol) was added and the mixture was stirred at room temperature for 30 min then at 80° C. for 2 hr. The resulting mixture was extracted with ethyl acetate (100 mL×4) and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 20: to 5:1) to obtain methyl 2-hydroxy-3-(isonicotinamido)benzoate as a solid (210 mg, yield 77%). LC-MS (ESI) m/z 273 [M+1]+.

Provenance & Evidence