反应详情

温度

0 °C

A mixture of 2-chloro-1-fluoro-4-nitrobenzene (2.0 g, 1.1 eq, 11.5 mmol) and tert-butyl (3S,4S)-3-fluoro-4-hydroxypiperidine-1-carboxylate (2.3 g, 1.0 eq, 10.5 mmol) was taken in annhydrous THF (50 mL) and stirred at 0° C. KOtBu (2.1 g, 1.8 eq, 18.9 mmol) was added to the above solution at 0° C. and the heterogeneous mixture was warmed to room temperature. Then the reaction mixture was refluxed overnight. After completion of the reaction, the mixture was concentrated under reduced pressure. EtOAc (100 mL) was added to the crude mixture and pardoned with aqueous saturated NaHCO3 (50 mL) solution. The layers were separated and the organic layer was washed with aqueous saturated NaHCO3 (50 mL) solution and brine (1×50 mL). The organic layers were dried over Na2SO4 and concentrated to leave cude solid. Purification of the crude mixture by column chromatography on silica gel (ISCO System) using EtOAc/hexane (gradient system from 0:1 to 2:8) as eluent gave the desired product in 63% yield.

1. temperaturethe heterogeneous mixture was warmed to room temperature
2. temperatureThen the reaction mixture was refluxed overnight
3. customAfter completion of the reaction
4. concentrationthe mixture was concentrated under reduced pressure
5. additionEtOAc (100 mL) was added to the crude mixture
6. customThe layers were separated
7. washthe organic layer was washed with aqueous saturated NaHCO3 (50 mL) solution and brine (1×50 mL)
8. dry with materialThe organic layers were dried over Na2SO4
9. concentrationconcentrated
10. customto leave cude solid
11. customPurification of the crude mixture by column chromatography on silica gel (ISCO System)