反应详情

温度

27 °C

A mixture of 9.180 liters of tetrahydrofuran and 0.460 liters of methanol at -10° C. and 7.650 liters of liquid ammonia was stirred for one hour at -35° to -40° C. and then 1.530 kg of 3α-hydroxy-7-keto-cholanic acid were added thereto over 15 minutes. 111 g of lithium were added with stirring at -35° to -38° C. over one hour to the mixture which was then stirred for one hour at -35° to -38° C. 1.530 liters of methanol were added to the mixture over 15 minutes and then 1.530 liters of demineralized water were added to the mixture over 15 minutes and stirring at 20° C. The ammonia was distilled and when the majority of the ammonia was evaporated, 7.650 liters of water were added to the mixture with stirring at 27°±2° C. Then, the tetrahydrofuran-methanol mixture was distilled off under reduced pressure at a bath temperature of 60° C. while progressively adding 1.530 liters of demineralized water to keep the volume constant and after cooling the mixture to about 27° C., 15,300 liters of water were added thereto. 7.650 liters of chloroform were added to the mixture with stirring and then 3,060 liters of 22° Be hydrochloric acid were added thereto over one hour at 27°±2° C. until a pH of 7 was obtained. At this point, acid addition was halted and the mixture was stirred for 30 minutes at 27°±2° C. after which the rest of the acid was added. The mixture was stirred for 2 hours at 27°±2° C. and was vacuum filtered with cotton cloth. The damp product was suspended in 2.300 liters of chloroform at 27°±2° C. and the suspension was stirred at 27°±2° C. for 15 minutes and was vacuum filtered. The product was resuspended in 2300 liters of chloroform at 27°±2° C. for 15 minutes and the suspension was vacuum filtered. The product was washed several times with water and dried at 60° C. to obtain 1.320 g of ursodesoxycholic acid melting at 198° C. and having a specific rotation of [α]D20 =+55.5°±0.5° (c=5% in ethanol).

1. stirringwas then stirred for one hour at -35° to -38° C
2. stirringstirring at 20° C
3. distillationThe ammonia was distilled
4. customwhen the majority of the ammonia was evaporated
5. addition7.650 liters of water were added to the mixture
6. stirringwith stirring at 27°±2° C
7. distillationThen, the tetrahydrofuran-methanol mixture was distilled off under reduced pressure at a bath temperature of 60° C.
8. additionwhile progressively adding 1.530 liters of demineralized water
9. addition15,300 liters of water were added
10. addition7.650 liters of chloroform were added to the mixture
11. stirringwith stirring
12. addition3,060 liters of 22° Be hydrochloric acid were added
13. customover one hour at 27°±2° C. until a pH of 7 was obtained
14. additionAt this point, acid addition
15. stirringthe mixture was stirred for 30 minutes at 27°±2° C. after which the rest of the acid
16. additionwas added
17. stirringThe mixture was stirred for 2 hours at 27°±2° C.
18. filtrationfiltered with cotton cloth
19. customwas suspended in 2.300 liters of chloroform at 27°±2° C.
20. stirringthe suspension was stirred at 27°±2° C. for 15 minutes
21. filtrationfiltered
22. waitThe product was resuspended in 2300 liters of chloroform at 27°±2° C. for 15 minutes
23. filtrationfiltered
24. washThe product was washed several times with water
25. customdried at 60° C.