反应详情

60% Sodium hydride (0.274 g, 6.85 mmol) was added to a mixed solution of 3-cyano-2-hydroxypyridine (0.658 g, 5.48 mmol) in 1,2-dimethoxyethane (10 mL)-DMF (5 ml) under ice-cooling, and the mixture was stirred for 20 min. To the reaction solution was added lithium bromide (0.793 g, 9.13 mmol), and the mixture was stirred at room temperature for 1.5 hr. To the reaction solution was added a solution of tert-butyl (6S,7R)-7-(4-chloro-3-fluorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylate (2 g, 4.57 mmol) in 1,2-dimethoxyethane (10 ml), and the mixture was stirred at 60° C. overnight. The reaction mixture was concentrated under reduced pressure, water 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 (1.757 g, 3.80 mmol, 83%).

1. temperaturecooling
2. stirringthe mixture was stirred at room temperature for 1.5 hr
3. stirringthe mixture was stirred at 60° C. overnight
4. concentrationThe reaction mixture was concentrated under reduced pressure, water
5. additionwas added to the residue
6. extractionthe mixture was extracted with ethyl acetate
7. washThe extract was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. customThe solvent was evaporated under reduced pressure
10. customThe residue was purified by silica gel column chromatography