反应详情

温度

0 °C

(1S,2R,5S)-5-Methyl-2-(1-methylethyl)cyclohexyl 2-oxo-3-piperidinecarboxylate (1 wt) is dissolved in ethanol (1.5 vol) and N-fluorobenzenesulfonimide (NFSI) (1.07 wt) added, followed by [(S)-BINAP]Pd(CH3CN)2(OTf)2 (0.038 wt) at 20° C. Residual NFSI and catalyst were washed in with ethanol (3 vol). The jacket is cooled to 0° C. and 2,6-lutidine (0.21 vol) charged slowly, maintaining the temperature below 20° C. The jacket temperature is then raised to 20° C. The reaction mixture is stirred for 24 h, cooled to 0° C. and stirred for an additional 2 h. The solids are isolated by filtration, washing with ethanol (3 vol) and dried under vacuum at 40° C. The dried crude solid is charged to a reactor, and dichloromethane (5 vol) added. The dichloromethane phase is washed sequentially with 2M aqueous NaOH (3 vol), water (3 vol), 5% w/w aqueous HCl (3 vol) and water (3 vol). The dichloromethane extract is transferred to a rotary evaporator and solvent swapped with n-heptane under reduced pressure to give a mobile slurry and a final volume of ca 11 vol. The product is isolated by filtration, washed with heptane (3 vol) and dried under vacuum at 40° C.

1. washResidual NFSI and catalyst were washed in with ethanol (3 vol)
2. addition2,6-lutidine (0.21 vol) charged slowly
3. temperaturemaintaining the temperature below 20° C
4. temperatureThe jacket temperature is then raised to 20° C
5. temperaturecooled to 0° C.
6. stirringstirred for an additional 2 h
7. customThe solids are isolated by filtration
8. washwashing with ethanol (3 vol)
9. customdried under vacuum at 40° C
10. customThe dried crude solid
11. additionis charged to a reactor
12. additiondichloromethane (5 vol) added
13. washThe dichloromethane phase is washed sequentially with 2M aqueous NaOH (3 vol), water (3 vol), 5% w/w aqueous HCl (3 vol) and water (3 vol)
14. extractionThe dichloromethane extract
15. customis transferred to a rotary evaporator and solvent
16. customto give a mobile slurry
17. customa final volume of ca 11 vol. The product is isolated by filtration
18. washwashed with heptane (3 vol)
19. customdried under vacuum at 40° C.