Methyl 2-chloronicotinate

67-56-1

2942-59-8

40134-18-7

(1) Preparation of methyl 2-chloronicotinate: 15.0 g (95.2 mmol) of 2-chloronicotinate was dissolved in 150 mL of dichloromethane and 8.37 mL (94.5 mmol) of oxalyl chloride was added slowly and dropwise. Subsequently, N,N-dimethylformamide was added dropwise to the mixture and the reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, 40.1 mL (286 mmol) of triethylamine and 37 mL (914 mmol) of methanol were added dropwise to the reaction mixture under ice-bath cooling conditions and stirring was continued for 30 minutes under ice-bath cooling. The reaction mixture was concentrated under reduced pressure and neutralized by adding aqueous sodium bicarbonate to the residue. The aqueous phase was extracted with ether, the organic phases were combined, washed with water, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (eluent: ethyl acetate/hexane=1:4) to afford 13.9 g of the target product methyl 2-chloronicotinate as a pale yellow liquid in 86% yield.1H-NMR (CDCl3/TMS, δ ppm): 3.97 (3H, s), 7.33 (1H, dd), 8.17 (1H, dd), 8.53 (1H, dd ).