Isopropanol → 6-Chloro-5-methylnicotinic acid isopropyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-chloro-5-methyl-nicotinic acid (21.64 g, 126 mmol) in isopropanol (450 mL), trimethylsilyl chloride (160 mL) is added dropwise. Upon completion of the addition, the mixture is heated to 70° C. and stirring is continued for 18 h. The mixture is diluted with diethyl ether (500 mL) and washed with sat. aq. NaHCO3 solution (5×50 mL). The washings are extracted back with diethyl ether (100 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 6:1 to give 6-chloro-5-methyl-nicotinic acid isopropyl ester (6.09 g) as a colourless oil; LC-MS: tR=0.97 min, [M+1]+=214.03. 1H NMR (D6-DMSO): δ 1.34 (d, J=6.3 Hz, 6H), 2.41 (s, 3H), 5.11-5.22 (m, 1H), 8.27 (s, 1H), 8.73 (s, 1H).

Provenance & Evidence