反应详情

To a solution of 2-methoxy-2,8-diazaspiro[4,5]decane-1,3-dione hydrochloride (1.5 g) in dimethylformamide (100 ml) were added triethylamine (1 ml), 4-(tert-butyloxycarbonylamino)butyric acid (2.03 g), N-hydroxybenztriazole (1.35 g) and dicylohexylcarbodiimide (2.06 g) in sequential additions, and this was followed by stirring at room temperature for 5 hours. The resulting precipitates were then removed. The solvent was evaporated under reduced pressure, and the resulting residual oily substance was dissolved in dichloromethane (50 ml), after which it was washed with a 10% aqueous solution of citric acid and then with water. The organic layer was then dried with anhydrous magnesium sulfate, and this was followed by the evaporation of the solvent under reduced pressure. The resulting residual oil was separated by silica gel column chromatography (eluent; chloroform-acetone-methanol=10:3:2 (v/v)). To the resulting oily substance containing the desired product was added a solution of 6N hydrogen chloride in ethanol (20 ml), and it was kept standing at room temperature for 10 minutes. The solvent was then evaporated under reduced pressure. The resulting oily substance was separated by silica gel column chromatography (eluent; chloroform-methanol-water=14:6:1) to obtain 1.2 g of a noncrystalline solid.

1. customThe resulting precipitates
2. customwere then removed
3. customThe solvent was evaporated under reduced pressure
4. dissolutionthe resulting residual oily substance was dissolved in dichloromethane (50 ml)
5. washafter which it was washed with a 10% aqueous solution of citric acid
6. dry with materialThe organic layer was then dried with anhydrous magnesium sulfate
7. customthis was followed by the evaporation of the solvent under reduced pressure
8. customThe resulting residual oil was separated by silica gel column chromatography (eluent; chloroform-acetone-methanol=10:3:2 (v/v))
9. additionTo the resulting oily substance containing the desired product
10. additionwas added a solution of 6N hydrogen chloride in ethanol (20 ml), and it
11. waitwas kept standing at room temperature for 10 minutes
12. customThe solvent was then evaporated under reduced pressure
13. customThe resulting oily substance was separated by silica gel column chromatography (eluent; chloroform-methanol-water=14:6:1)