反应详情

温度

80 °C

Sodium hydrogen carbonate (2.53 g, 30.14 mmol) and hydroxylamine monohydrochloride (2.094 g, 30.14 mmol) were added to a solution of tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-1,4-oxazepane-4-carboxylate (1.74 g, 3.77 mmol) in DMSO (4 mL), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added 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 dissolved in THF (15 mL), diazabicycloundecene (0.564 mL, 3.77 mmol) and 1,1′-carbonyldiimidazole (0.917 g, 5.66 mmol) were added, and the mixture was heated under reflux for 2 hr. The reaction mixture was concentrated under reduced pressure, 1 N hydrochloric acid was added to the residue, 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 to give the title compound (1.826 g, 3.51 mmol, 93%).

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. dissolutionThe residue was dissolved in THF (15 mL)
6. temperaturethe mixture was heated
7. temperatureunder reflux for 2 hr
8. concentrationThe reaction mixture was concentrated under reduced pressure, 1 N hydrochloric acid
9. additionwas added to the residue
10. extractionthe mixture was extracted with ethyl acetate
11. washThe extract was washed with brine
12. dry with materialdried over anhydrous sodium sulfate
13. customThe solvent was evaporated under reduced pressure
14. customThe residue was purified by silica gel column chromatography