Acetic Anhydride → Abiraterone Acetate

温度

22.5 °C

1 l of THF was added to 100 g of abiraterone (0.286 mole). 44 g (1.5 eq.) of triethylamine, 1.75 g of 4-dimethylaminopyridine (2 molar %) and 35 g (1.2 eq.) of acetic anhydride were added to the slurry. The slurry was stirred for 24 hours at 20-25° C. (the mixture turned to solution at the end of the reaction which was monitored by HPLC). 0.7 l of toluene and 0.4 l of water were added to the mixture which was stirred for 1 h at 20-25° C. The mixture was clarified on a cake of Clarcel®. The two layers were separated and the organic layer was washed with 0.1 l of water. The organic layer was concentrated at 40° C. to dryness under vacuum. 100 ml of ethanol and 900 ml of n-hexane were then added and the mixture was heated to 55-60° C. to dissolve (the solution was still cloudy). 5 wt % of 2S activated charcoal and 5 wt % of Clarcel® were added to the mixture which was maintained 30 minutes at 55-60° C. The Clarcel® and the charcoal were then filtered at 55-60° C. and washed twice with 0.1 l of ethanol. The ethanol was then partially removed by distillation under vacuum at 40±5° C. The mixture was cooled to 20° C., then to 0-5° C. and maintained 1 hour at this temperature. The suspension was filtered and the cake was washed twice with 0.1 l of n-hexane at 0-5° C. The wet abiraterone acetate was dried at 50° C. under vacuum to give 90 g (0.23 mole) of the pure abiraterone acetate (up to 99.0% by HPLC) 90% yield from the abiraterone. The overall yield from DHEA was around 43-45%.

1. customturned to solution at the end of the reaction which
2. stirringwas stirred for 1 h at 20-25° C
3. customThe two layers were separated
4. washthe organic layer was washed with 0.1 l of water
5. concentrationThe organic layer was concentrated at 40° C. to dryness under vacuum
6. addition100 ml of ethanol and 900 ml of n-hexane were then added
7. temperaturethe mixture was heated to 55-60° C.
8. dissolutionto dissolve (the solution
9. addition5 wt % of 2S activated charcoal and 5 wt % of Clarcel® were added to the mixture which
10. temperaturewas maintained 30 minutes at 55-60° C
11. filtrationThe Clarcel® and the charcoal were then filtered at 55-60° C.
12. washwashed twice with 0.1 l of ethanol
13. customThe ethanol was then partially removed by distillation under vacuum at 40±5° C
14. temperatureThe mixture was cooled to 20° C.
15. temperatureto 0-5° C. and maintained 1 hour at this temperature
16. filtrationThe suspension was filtered
17. washthe cake was washed twice with 0.1 l of n-hexane at 0-5° C
18. dry with materialThe wet abiraterone acetate was dried at 50° C. under vacuum

ORDレコード

ord-00bd164781bd43b8b9b24098047ba231

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09353145B2