反应详情

tert-Butyl[(1S)-1-formylpropyl]carbamate (24.00 g) and ethyl bromodifluoroacetate (77.0 g) were dissolved in tetrahydrofuran (220 mL), and to a suspension of a zinc powder (25.4 g) in tetrahydrofuran (50 mL) was added dropwise the solution at room temperature. After heating under reflux for 1 hr, the mixture was cooled to room temperature, 1 mol/L aqueous potassium hydrogen sulfate solution (400 mL) was added, and the mixture was extracted with ethyl acetate. The extracted organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=10→40%), the obtained oil was dissolved in 4 mol/L hydrogen chloride/ethyl acetate solution (150 mL), and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (600 mL). Diisopropylethylamine (32.8 mL) was added, and the mixture was heated under reflux for 4 hr. The reaction solution was concentrated under reduced pressure, the residue was filtered through silica gel, and the filtrate was concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate/hexane to give the title compound as a white powder (yield: 7.20 g, 54%).

1. additionwas added dropwise the solution at room temperature
2. temperatureAfter heating
3. temperatureunder reflux for 1 hr
4. extractionthe mixture was extracted with ethyl acetate
5. washThe extracted organic layer was washed with water and saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=10→40%)
9. dissolutionthe obtained oil was dissolved in 4 mol/L hydrogen chloride/ethyl acetate solution (150 mL)
10. concentrationThe reaction solution was concentrated under reduced pressure
11. dissolutionthe residue was dissolved in tetrahydrofuran (600 mL)
12. additionDiisopropylethylamine (32.8 mL) was added
13. temperaturethe mixture was heated
14. temperatureunder reflux for 4 hr
15. concentrationThe reaction solution was concentrated under reduced pressure
16. filtrationthe residue was filtered through silica gel
17. concentrationthe filtrate was concentrated under reduced pressure
18. customThe obtained residue was recrystallized from ethyl acetate/hexane