Hydrochloric Acid → Ethyl 4-chloro-6-methylpyridine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 6-methylpyridine-2-carboxylate N-oxide (2.29 g), a 4N solution of hydrogen chloride in ethyl acetate (5 ml) and ethyl acetate (15 ml) was stirred at room temperature for 30 minutes. The reaction mixture was concentrated and the resultant residue was combined with phosphorus oxychloride (17.90 g), and stirred at 90° C. for 2 hours with heating. The reaction mixture was concentrated, and the resultant residue was diluted with ice-water and then combined with an aqueous solution of potassium carbonate to make the solution basic. The mixture was extracted with dichloromethane, and the organic phase was dried and concentrated. A solution of the residue obtained and triethylamine (5 ml) in ethanol (50) was heated under reflux for 10 hours. The reaction mixture was concentrated, and the residue was combined with water and ethyl acetate, and the organic phase was isolated, dried and concentrated to obtain the title compound (1.74 g) as a tan oil.

Provenance & Evidence