Synthesis
The general procedure for the synthesis of 2-acetyl-6-methylpyridine from 1-(6-methylpyridin-2-yl)ethan-1-ol is as follows: to a solution of oxalyl chloride (20 mL, 225 mmol, 1.1 eq.) in dichloromethane (300 mL) was slowly added a solution of dimethyl sulfoxide (32 mL, 2.2 eq.) in dichloromethane (400 mL) at -75 °C for 1 hour. The resulting solution was stirred at -75 °C for 10 minutes, then a dichloromethane (600 mL) solution of 1-(6-methylpyridin-2-yl)ethan-1-ol (28 g, 204 mmol, 1 equiv) was slowly added. The reaction mixture was continued to be stirred at the same temperature for 10 minutes, followed by the slow addition of triethylamine (140 mL, 1.02 mol, 5 eq.). The reaction mixture was gradually warmed to 20 °C and stirred for 2 h, after which the reaction was quenched with water (500 mL). The organic phase was separated, dried over magnesium sulfate and concentrated in vacuum to give the crude product. Purification by silica gel column chromatography (eluent ratio 3:1 hexane/ethyl acetate) afforded 2-acetyl-6-methylpyridine (25.36 g, 92% yield).
