反应详情

Concentrated sulfuric acid (4 mL) was added to a solution of 5-chloropyridine-2-carboxylic acid (25.3 g) in ethanol (500 mL) under ice-cooling, and the mixture was stirred under reflux for four hours. The reaction solution was cooled to room temperature and water was added, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform only→hexane:ethyl acetate=1:1) and the solvent was evaporated under reduced pressure from the fraction containing ethyl 5-chloropyridine-2-carboxylate. Urea peroxide (30.2 g) was added to a solution of the residue in chloroform (300 mL) under ice-cooling. A mixture of trifluoroacetic anhydride (44.7 mL) and chloroform (300 mL) was added dropwise over 30 minutes, and the mixture was stirred while gradually returning to room temperature for two hours. A saturated sodium thiosulfate solution was added dropwise to the reaction solution, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give ethyl 5-chloropyridine-2-carboxylate 1-oxide as a yellow oil (36.8 g, quant.).

1. temperaturecooling
2. temperatureunder reflux for four hours
3. extractionfollowed by extraction with chloroform
4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
5. filtrationfiltered
6. customThe solvent was then evaporated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (chloroform only→hexane
8. customethyl acetate=1:1) and the solvent was evaporated under reduced pressure from the fraction
9. additioncontaining ethyl 5-chloropyridine-2-carboxylate
10. additionUrea peroxide (30.2 g) was added to a solution of the residue in chloroform (300 mL) under ice-
11. temperaturecooling
12. additionA mixture of trifluoroacetic anhydride (44.7 mL) and chloroform (300 mL)
13. additionwas added dropwise over 30 minutes
14. stirringthe mixture was stirred
15. additionA saturated sodium thiosulfate solution was added dropwise to the reaction solution
16. extractionfollowed by extraction with chloroform
17. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
18. filtrationfiltered
19. customThe solvent was then evaporated under reduced pressure
20. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)