Reacción #720603

Ecuación de reacción

2-chloro-1-fluoro-4-nitrobenzene

tert-butyl (3S,4S)-3-fluoro-4-hydroxypiperidine-1-carboxylate

KOtBu

→

desired product

Rendimiento 63.0%

tert-butyl (3S,4S)-4-(2-chloro-4-nitrophenoxy)-3-fluoropiperidine-1-carboxylate

Rendimiento 63.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe heterogeneous mixture was warmed to room temperature
2. 2
   TemperaturaThen the reaction mixture was refluxed overnight
3. 3
   OtroAfter completion of the reaction
4. 4
   Concentraciónthe mixture was concentrated under reduced pressure
5. 5
   workup.ADDITIONEtOAc (100 mL) was added to the crude mixture
6. 6
   OtroThe layers were separated
7. 7
   Lavadothe organic layer was washed with aqueous saturated NaHCO3 (50 mL) solution and brine (1×50 mL)
8. 8
   SecadoThe organic layers were dried over Na2SO4
9. 9
   Concentraciónconcentrated
10. 10
    Otroto leave cude solid
11. 11
    OtroPurification of the crude mixture by column chromatography on silica gel (ISCO System)

Procedimiento

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.

Fuente