反应详情

温度

40 °C

A hydrogenation vessel was charged with a methanol (1000 mL) slurry of tert-butyl ((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)carbamate (164 g, 0.50 mol) (Wang et al., U.S. Pat. No. 6,995,174) and 5% Ru/C (dry, 7.5 wt %, 12.4 g) and set stirring. The vessel was placed under nitrogen (20 psig) and vented to atmospheric pressure three times to remove residual oxygen. The vessel was then placed under hydrogen (50 psig). After 20 hours, the vessel was vented to atmospheric pressure. The reaction slurry was then transferred out of the reaction and filtered through SOLKA FLOK (34 grams, wetted w/100 mL methanol) to yield a clear, light brown solution. The SOLKA FLOK was rinsed with methanol (200 mL×2). The combined methanol solutions were concentrated under reduced pressure to yield crude product as a white solid (153 g). The crude product was slurried in ethyl acetate (800 mL), warmed to 40° C. and aged 30 minutes. The solution was then seeded, aged 30 minutes, and heptane (500 mL) was added via addition funnel over 30 minutes. The partially crystallized solid was cooled to room temperature and aged overnight after which additional heptane (500 mL) was added. After one hour, additional heptane (250 mL) was added via addition funnel, and the white slurry aged for one hour. The solution was filtered and the solid was rinsed with heptane/EtOAc (500 mL, 4:1) and dried under reduced pressure to give tert-butyl ((1R,2R)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-ethylcyclopropyl)carbamate (125.9 g).

1. customto remove residual oxygen
2. customThe reaction slurry was then transferred out of the reaction
3. filtrationfiltered through SOLKA FLOK (34 grams, wetted w/100 mL methanol)
4. customto yield a clear, light brown solution
5. washThe SOLKA FLOK was rinsed with methanol (200 mL×2)
6. concentrationThe combined methanol solutions were concentrated under reduced pressure
7. customto yield crude product as a white solid (153 g)
8. waitaged 30 minutes
9. additionwas added
10. waitAfter one hour
11. waitthe white slurry aged for one hour
12. filtrationThe solution was filtered
13. washthe solid was rinsed with heptane/EtOAc (500 mL, 4:1)
14. customdried under reduced pressure