2-Chloroisonicotinic acid → Methyl 2-chloropyridine-4-carboxylate

Participants

Reaction Steps

2-Chloropyridine-4-carboxylic acid (15.5 g, 98 mmol) was suspended in methanol (175 ml) and anhydrous hydrogen chloride gas was slowly bubbled through the reaction mixture while cooling in a methanol/water (20/80) dry ice bath. Bubbling was continued for 40 min. during which time the suspension cleared to a partial solution. Ice bath was removed and the reaction mixture was heated to reflux under anhydrous conditions for 30 min. to give a clear yellow solution. The solution was cooled in an ice bath and saturated sodium bicarbonate was slowly added with stirring till the pH was neutral. The organics were removed in vacuo and the product was extracted into ethyl acetate. The ethyl acetate layer was dried over sodium sulfate, filtered, and concentrated in vacuo to yield 2-chloropyridine-4-carboxylic acid methyl ester as a brown liquid.

Provenance & Evidence