2-Chloropyridine-4-carboxylic acid tert-butyl ester

6313-54-8

36805-97-7

295349-62-1

General procedure for the synthesis of tert-butyl 2-chloroisonicotinate from 2-chloroisonicotinic acid and N,N-dimethylformamide di-tert-butyl acetal: 10.0 g (63.4 mmol) of 2-chloroisonicotinic acid was dissolved in 100 ml of chloroform and heated to reflux temperature. A total of 91.2 ml (380 mmol, 6 eq.) of N,N-dimethylformamide di-tert-butyl acetal was added in three additions of 30.4 ml each at the beginning of the reaction, after 1 h and after 2 h. Upon completion of the reaction, it was cooled down to room temperature, and the reaction mixture was diluted with ethyl acetate, washed with water, sodium bicarbonate solution, and saturated saline in that order, and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (fast column chromatography, eluent gradient from hexane to hexane/ethyl acetate 95/5) to give 7.6 g (35.6 mmol, 56% yield) of white solid product. Mass spectrum (LC/MS): m/z 158 = [M + H - tBu]+. 1H-NMR (300 MHz, CDCl3): δ 8.55 (d, 1H), 7.85 (s, 1H), 7.76 (d, 1H), 1.64 (s, 9H).