Thionyl Chloride → 6-Chloro-N-methoxy-N-methylnicotinamide

Participants

Reaction Steps

A mixture of 6-chloronicotinic acid (80 g, 0.48 mmol) and thionyl chloride (400 ml) was heated under reflux for 3 hours. The cooled mixture was evaporated under reduced pressure and the residue was dissolved in dichloromethane (600 ml). N,O-dimethylhydroxylamine hydrochloride (54.6 g, 0.56 mmol) was added to the mixture which was then cooled in ice and treated with triethylamine (200 ml). The suspension was stirred for 1 hour at room temperature and was then filtered. The filtrate was washed with dilute sodium hydroxide solution (2N, 300 ml), brine (200 ml) and dried (MgSO4). The solution was evaporated under reduced pressure then distilled to give the title compound, (90 g), b.p. 106°-110° C. at 0.5 mm.

Provenance & Evidence