反应详情

1.1 g of cesium carbonate (3.42 mmol) was added to a solution of 1.70 g of N-{(S)-2-[4-(2-chloro-5-fluorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (62e) (2.85 mmol) and 0.87 ml of thiophenol (content: 95%) (8.54 mmol) in N,N-dimethylformamide (15 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at the same temperature for one hour. 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=20/1-10/1). 0.99 ml of triethylamine (7.11 mmol) and 620 mg of di-t-butyl dicarbonate (2.84 mmol) were added to a solution of 4-{(S)-2-amino-2-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}-1-(2-chloro-5-fluorophenyl)-5,5-dimethylpiperazin-2-one obtained above in methylene chloride (24 ml), and the mixture was stirred at room temperature for 15 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/ethyl acetate=3/1) to obtain 1.05 g of the title compound (yield: 70%).

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=20/1-10/1)
6. stirringthe mixture was stirred at room temperature for 15 hours
7. extractionfollowed by extraction with methylene chloride
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/ethyl acetate=3/1)