Diethyl Malonate → 2-Methyl-5-nitropyridine

Participants

Reaction Conditions

Reaction Steps

A slurry of diethyl malonate (42 mL, 0.28 mol) and sodium (4.71 g, 0.20 mol) was warmed slowly to 90° C. The slurry was stirred at 90° C. for 2 h, at 120° C. for 30 min before being cooled to room temperature. Toluene (200 mL) and 2-chloro-5-nitropyridine (25.0 g, 0.16 mmol) were added and the slurry was heated at 110° C. for 1.5 h at ambient temperature for 17 h. After evaporation of the volatiles, 6 N HCl (200 mL) was added, the slurry was heated to reflux for 4 h and then cooled to room temperature. The solution was neutralized with solid sodium carbonate, extracted with EtOAc (6×100 mL), dried over solid magnesium sulfate, and concentrated to a dark solid. This material was flashed through a plug of silica gel (2″×2″, eluant=20% EtOAc/petroleum ether) to afford 2-methyl-5-nitropyridine as a tan solid (15.2 g).

Provenance & Evidence