反应详情

温度

40 °C

A hydrogenation vessel was charged with a MeOH (1000 mL) slurry of t-butyl ((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)carbamate (164 g, 0.50 mol) (U.S. Pat. No. 6,995,174) and 5% Ru/C (dry, 7.5 wt %, 12.4 g) and stirred. The vessel was placed under N2 (20 psi) and vented to atmospheric pressure (3×) to remove residual oxygen. The vessel was then placed under H2 (50 psi). After 20 hours, the vessel was vented to atmospheric pressure. The reaction slurry was then transferred out of the reaction vessel and filtered through SOLKA FLOK (34 g, wetted with 100 mL MeOH) to yield a clear, light brown solution. The SOLKA FLOK was rinsed with MeOH (200 mL×2). The combined MeOH solutions were concentrated under reduced pressure to yield crude product as a white solid (153 g). The crude product was slurried in EtOAc (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 RT and aged overnight, after which additional heptane (500 mL) was added. After 1 hour, additional heptane (250 mL) was added via addition funnel, and the white slurry aged for 1 hour. The solution was filtered, and the solid was rinsed with heptane/EtOAc (500 mL, 4:1) and dried under reduced pressure to give t-butyl ((1R,2R)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-ethylcyclopropyl)carbamate (125.9 g).

1. customto remove residual oxygen
2. filtrationfiltered through SOLKA FLOK (34 g, wetted with 100 mL MeOH)
3. customto yield a clear, light brown solution
4. washThe SOLKA FLOK was rinsed with MeOH (200 mL×2)
5. concentrationThe combined MeOH solutions were concentrated under reduced pressure
6. customto yield crude product as a white solid (153 g)
7. waitaged 30 minutes
8. temperatureThe partially crystallized solid was cooled to RT and aged overnight
9. waitAfter 1 hour
10. waitthe white slurry aged for 1 hour
11. filtrationThe solution was filtered
12. washthe solid was rinsed with heptane/EtOAc (500 mL, 4:1)
13. customdried under reduced pressure