Ethanol → Ethyl chloronicotinate

Participants

Reaction Steps

To a mixture of 2-hydroxynicotinic acid (13.91 g., 0.1 mole) and phosphorus pentachloride (42 g., 0.2 mole) was added phosphorus oxychloride (25 ml., excess) and then stirred at room temperature for 30 minutes. This was then heated at 120° C. for 2 hours. The reaction mixture was then concentrated in vacuo until a red viscous mass was obtained. The latter was cooled in an ice water bath and 45 ml. absolute ethanol was added first slowly and then rapidly. It was then refluxed for 30 min. and cooled. Most of the excess ethanol was removed under vacuo and the remaining mass was diluted with water (90 ml.). The aqueous solution was neutralized with 10% sodium carbonate solution and then extracted with 2×100 ml. portions of dichloromethane. The organic layer was washed with 2N NaOH solution followed by water and brine. It was dried and then concentrated to give a pale yellow liquid which was purified by distillation under reduced pressure (20 mm. Hg, b.p. 140°-44° C.) to give ethyl 2-chloronicotinate in 60-65% yield. A fore-run at 80°-110° C. (5-10%) was discarded which consisted mainly of ethyl 2-ethoxynicotinate.

Provenance & Evidence