反应详情

温度

80 °C

Sodium hydrogen carbonate (829 mg, 9.87 mmol) and hydroxylamine hydrochloride (686 mg, 9.87 mmol) were added to a solution of tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (590 mg, 1.23 mmol) in DMSO (4 mL), and the mixture was stirred at 80° C. for 5 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was diluted with THF (10 mL), diazabicycloundecene (0.184 mL, 1.23 mmol) and carbonyl-1,1′-bisimidazole (299 mg, 1.85 mmol) were added, and the mixture was stirred at 70° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was acidified with 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and recrystallized from ethanol-hexane to give the title compound (480 mg, 0.893 mmol, 72.6%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe extract was washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was evaporated under reduced pressure
5. additionwere added
6. stirringthe mixture was stirred at 70° C. for 2 hr
7. concentrationThe reaction mixture was concentrated under reduced pressure
8. extractionthe mixture was extracted with ethyl acetate
9. washThe extract was washed with brine
10. dry with materialdried over anhydrous sodium sulfate
11. customThe solvent was evaporated under reduced pressure
12. customThe residue was purified by silica gel column chromatography
13. customrecrystallized from ethanol-hexane