Diethyl Malonate → 2-Methyl-5-nitropyridine

Temperature

110 °C

The 2-methyl-5-nitropyridine of formula (BB) was prepared according to prior art literature (Odashima, T.; Sakakura, K.; Kohata, K.; Ishii, H., Bull. Chem. Soc. Jpn., 1993, 66, 797 and references therein). A reaction vessel charged with diethyl malonate (12.5 g, 78.0 mmol) in diethyl ether (450 mL) was further charged with sodium hydride (3.2 g of a 60% slurry in mineral oil, 79 mmol). When the evolution of hydrogen gas subsided, the 2-chloro-5-nitropyridine of formula (AA) (12.5 g, 79.0 mmol) was charged to the vessel with stirring. The solvent was then removed by evaporation and the red, tarry residue was heated to 110° C. for 1 hour. At this point, 6 M H2SO4 (90 mL) was charged to the vessel and the mixture was heated to reflux overnight. The solution was cooled in an ice bath and was neutralized with potassium hydroxide solution. The solids were removed by filtration and washed with chloroform. The filtrate was extracted with chloroform and the combined chloroform fractions were evaporated. The resulting crude material was purified by flash chromatography to yield 6.1 g (56%) of the 2-methyl-5-nitropyridine of formula (BB) as a pale orange solid.

1. customThe 2-methyl-5-nitropyridine of formula (BB) was prepared
2. customThe solvent was then removed by evaporation
3. additionAt this point, 6 M H2SO4 (90 mL) was charged to the vessel
4. temperaturethe mixture was heated
5. temperatureto reflux overnight
6. temperatureThe solution was cooled in an ice bath
7. customThe solids were removed by filtration
8. washwashed with chloroform
9. extractionThe filtrate was extracted with chloroform
10. customthe combined chloroform fractions were evaporated
11. customThe resulting crude material was purified by flash chromatography

ORD record

ord-ed66a239a81546c093198295f88f4499

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445694B2