Diethyl Malonate → 2-Methyl-3-nitropyridine

Into a flask containing diethyl malonate (20 g, 0.125 mol) was added sodium (2.0 g, 0.087 mol). The reaction mixture was stirred for 1 h at room temperature and then allowed to warm to 120° C. (oil bath temperature) for 50 min. To this yellow suspension of the solid mass was added toluene (120 mL) followed by addition of a solution of 2-chloro-3-nitropyridine 1 (12.8 g, 0.08 mol) in 40 mL of toluene. The reaction mixture was refluxed for 8 h, and then stirred overnight at room temperature. The solvent was removed under reduced pressure and the residue was dissolved in 30% H2SO4 (60 mL). This reaction mixture was heated to 125° C. (oil bath) for 7 h, cooled and poured into ice (200 g). The reaction mixture was neutralized with saturated NaHCO3 solution, filtered through Celite, extracted several times with ether. The combined extracts were dried over anhydrous Na2SO4. The solvent was evaporated and the residue was distilled under reduced pressure to provide 6.65 g (60%) of the desired product 3.

1. temperatureto warm to 120° C. (oil bath temperature) for 50 min
2. additionTo this yellow suspension of the solid mass
3. temperatureThe reaction mixture was refluxed for 8 h
4. stirringstirred overnight at room temperature
5. customThe solvent was removed under reduced pressure
6. dissolutionthe residue was dissolved in 30% H2SO4 (60 mL)
7. temperatureThis reaction mixture was heated to 125° C. (oil bath) for 7 h
8. temperaturecooled
9. additionpoured into ice (200 g)
10. filtrationfiltered through Celite
11. extractionextracted several times with ether
12. dry with materialThe combined extracts were dried over anhydrous Na2SO4
13. customThe solvent was evaporated
14. distillationthe residue was distilled under reduced pressure

ORD record

ord-77084a7ab2c34553b95fcbdc80f7391c

Source dataset

uspto-grants-1999_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05869676