反应详情

To a solution of ethyl 4-[(tert-butoxycarbonyl)amino]-2,2-difluoro-3-{[(4-methylphenyl)sulfonyl]oxy}butanoate (44.8 g) in ethyl acetate (50 mL) was added 4 mol/L hydrogen chloride-ethyl acetate solution (100 mL), and the mixture was stirred for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was azeotropically distilled twice with toluene. The obtained mixture was dissolved in acetonitrile (20 mL), triethylamine (15.6 g) was added, and the mixture was stirred for 3 hr. Di-tert-butyl bicarbonate (33.6 g) and 4-dimethylaminopyridine (3.76 g) were added at room temperature and the mixture was stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate, and washed with 1 mol/L hydrochloric acid. The separated aqueous layer was extracted again with ethyl acetate. Combined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=2:1) to give the title compound as a pale-yellow oil (yield 32.0 g, 80%).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. distillationthe residue was azeotropically distilled twice with toluene
3. dissolutionThe obtained mixture was dissolved in acetonitrile (20 mL)
4. additiontriethylamine (15.6 g) was added
5. stirringthe mixture was stirred for 3 hr
6. additionDi-tert-butyl bicarbonate (33.6 g) and 4-dimethylaminopyridine (3.76 g) were added at room temperature
7. stirringthe mixture was stirred for 1 hr
8. concentrationThe reaction mixture was concentrated under reduced pressure
9. dissolutionthe residue was dissolved in ethyl acetate
10. washwashed with 1 mol/L hydrochloric acid
11. extractionThe separated aqueous layer was extracted again with ethyl acetate
12. washCombined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=2:1)