Diethyl methylmalonate → 2-Ethyl-5-nitropyridine

Diethyl methylmalonate (52.2 g) was added dropwise to a suspension of sodamide (11.7 g) in dry THF (150 ml) with stirring at ambient temperature under nitrogen. The mixture was boiled under reflux for 1 hour and then a solution of 2-chloro-5-nitropyridine (47.7 g) in dry THF (150 ml) was added dropwise cautiously with stirring. After the addition the mixture was boiled under reflux for 3 hours, then cooled and evaporated to remove approximately 80% of the solvent. The residue was poured into water (1 l) and extracted with ether to give an oil which partially crystallised on standing. A mixture of the residue, concentrated sulphuric acid (50 ml) and water (25 ml) was boiled under reflux for 4 hours then cooled in ice and neutralised using concentrated aqueous sodium hydroxide solution. The mixture was left to stand at ambient temperature for 64 hours and then filtered to give a solid which was extracted continuously with dichloromethane in a soxhlet extractor. The dichloromethane was cooled, dried and evaporated. The residue was filtered and the filtrate was distilled under vacuum to give 2-ethyl-5-nitropyridine, b.p. 82°-92° C. at 1 mm Hg.

1. temperatureunder reflux for 1 hour
2. stirringwith stirring
3. additionAfter the addition the mixture
4. temperatureunder reflux for 3 hours
5. temperaturecooled
6. customevaporated
7. customto remove approximately 80% of the solvent
8. additionThe residue was poured into water (1 l)
9. extractionextracted with ether
10. customto give an oil which
11. custompartially crystallised on standing
12. additionA mixture of the residue, concentrated sulphuric acid (50 ml) and water (25 ml)
13. temperatureunder reflux for 4 hours
14. temperaturethen cooled in ice
15. waitThe mixture was left
16. filtrationfiltered
17. customto give a solid which
18. extractionwas extracted continuously with dichloromethane in a soxhlet extractor
19. temperatureThe dichloromethane was cooled
20. customdried
21. customevaporated
22. filtrationThe residue was filtered
23. distillationthe filtrate was distilled under vacuum

ORD record

ord-f605b6470a3d4e32bdd24ac52fb3d0a2

Source dataset

uspto-grants-1998_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05780482