N-methyl-2-pyrrolidone → 1,1-Dimethylethyl 5-chloro-6-methyl-3-pyridinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 5,6-dichloronicotinic acid tert.-butyl ester (3.37 g, 13.6 mmol), Fe(acac)3 (719 mg, 2.04 mmol) and NMP (1.95 mL, 20 mmol) in THF (300 mL), a solution of methylmagnesium chloride in THF (3 M, 5.4 mL, 16.3 mmol) is slowly added at −78° C. The brown solution turns turbid and black. Stirring is continued for 1 h at −75° C. before it is warmed to 0° C. The reaction is incomplete and the mixture is cooled again at −70° C. A further batch of methylmagnesium bromide in THF (3 M, 5.4 mL, 16.3 mmol) is slowly added at −70° C. The dark green mixture is slowly warmed to −20° C. and carefully quenched with 0.7 N aq. HCl (150 mL). The mixture is extracted with diethyl ether (5×60 mL). The combined org. extracts are dried over Na2SO4, filtered and evaporated to give crude 5-chloro-6-methyl-nicotinic acid tert.-butyl ester as a yellow oil (4.66 g); LC-MS: tR=1.03 min, [M+1]+=228.22.

Provenance & Evidence