Nicotinic Acid → Nicotinoyl chloride

Participants

Reaction Steps

Thionyl chloride (10 mL) was added to nicotinic acid (370 mg, 3.0 mmol) and the mixture was stirred under reflux for 6 hr. Thionyl chloride was evaporated under reduced pressure and the residues was dried in vacuum to yield nicotinoyl 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. Then nicotinoyl chloride (420 mg, 3.0 mmol) was added. 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-(nicotinamido)benzoate as a solid (215 mg, yield 79%). LC-MS (ESI) m/z 273 [M+1]+.

Provenance & Evidence