反应详情

Next, anhydrous ether (19 ml) was added to lithium aluminum hydride (257 mg, 6.77 mmol) under a nitrogen atmosphere, and the mixture was stirred under ice-cooling. A solution of 4-(4-pyridyl)-2-butanone oxime (556 mg, 3.38 mmol) in ether (15 ml) was added dropwise to the mixture over seven minutes, and the whole was stirred at room temperature overnight. Further, the mixture was refluxed for two days and then stirred under ice-cooling. Ethyl acetate was slowly added to the reaction mixture, and then a 1 N aqueous sodium hydroxide solution (slowly at first, total: 20 ml) was added thereto. Chloroform (80 ml) was added thereto, and the resulting insoluble matter was filtered out with Celite. After separation, chloroform in the organic layer was evaporated under reduced pressure. The residue was combined with the aqueous layer, tetrahydrofuran (20 ml) was added thereto, and the whole was stirred at room temperature. Di-t-butyl carbonate (1.48 g, 6.78 mmol) was added thereto. The whole was stirred overnight and extracted with chloroform (50 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography. A 4 N solution of hydrogen chloride in ethyl acetate (3 ml) and ethanol (1 ml) were added to the residue, and the whole was stirred at room temperature. After three hours, the reaction mixture was concentrated under reduced pressure, chloroform (5 ml), methanol (5 ml) and triethylamine (1 ml) were added to the residue, the whole was concentrated under reduced pressure, and the residue was purified by basic silica gel column chromatography to give the target compound (161 mg, 32%) as a brown oily matter.

1. temperaturecooling
2. stirringthe whole was stirred at room temperature overnight
3. temperatureFurther, the mixture was refluxed for two days
4. stirringstirred under ice-
5. temperaturecooling
6. filtrationthe resulting insoluble matter was filtered out with Celite
7. customAfter separation, chloroform in the organic layer
8. customwas evaporated under reduced pressure
9. additionwas added
10. stirringthe whole was stirred at room temperature
11. stirringThe whole was stirred overnight
12. extractionextracted with chloroform (50 ml)
13. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography
16. additionA 4 N solution of hydrogen chloride in ethyl acetate (3 ml) and ethanol (1 ml) were added to the residue
17. stirringthe whole was stirred at room temperature
18. concentrationthe reaction mixture was concentrated under reduced pressure, chloroform (5 ml), methanol (5 ml) and triethylamine (1 ml)
19. additionwere added to the residue
20. concentrationthe whole was concentrated under reduced pressure
21. customthe residue was purified by basic silica gel column chromatography