Diethyl Malonate → 2-Methyl-5-nitropyridine

Temperature

120 °C

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).

1. temperaturebefore being cooled to room temperature
2. temperaturethe slurry was heated at 110° C. for 1.5 h at ambient temperature for 17 h
3. customAfter evaporation of the volatiles, 6 N HCl (200 mL)
4. additionwas added
5. temperaturethe slurry was heated
6. temperatureto reflux for 4 h
7. temperaturecooled to room temperature
8. extractionextracted with EtOAc (6×100 mL)
9. dry with materialdried over solid magnesium sulfate
10. concentrationconcentrated to a dark solid

ORD record

ord-90ee8ffedb6048b38083e24393c3a315

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06916814B2