反应详情

585 mg of cesium carbonate (1.8 mmol) was added to a solution of 888 mg of N-{(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4R)-5-oxo-4-propyltetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (116h) (1.50 mmol) and 0.46 ml of thiophenol (content: 95%) (4.5 mmol) in acetonitrile (15 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at the same temperature for 2.5 hours. Brine was added to the reaction mixture, followed by extraction with methylene chloride. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=50/1-10/1). 94 mg of sodium bicarbonate (1.12 mmol) and 245 mg of di-t-butyl dicarbonate (1.12 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4R)-5-oxo-4-propyltetrahydrofuran-2-yl]ethyl}-1-(2-chlorophenyl)-5,5-dimethylpiperazin-2-one obtained above in ethyl acetate (5 ml)-water (5 ml), and the mixture was stirred at room temperature overnight. Brine was added to the reaction mixture, followed by extraction with ethyl acetate. Then, the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=40/1-20/1) to obtain 418 mg of the title compound (yield: 55%).

1. extractionfollowed by extraction with methylene chloride
2. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
3. filtrationAfter filtration
4. customthe solvent was evaporated under reduced pressure
5. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=50/1-10/1)
6. stirringthe mixture was stirred at room temperature overnight
7. extractionfollowed by extraction with ethyl acetate
8. dry with materialThen, the organic layer was dried over anhydrous magnesium sulfate
9. filtrationAfter filtration
10. customthe solvent was evaporated under reduced pressure
11. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=40/1-20/1)