Reaktion #618395

Reaktionsgleichung

triethylamine

acetic anhydride

THF

abiraterone

→

abiraterone acetate

Lösungsmittel

water

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeturned to solution at the end of the reaction which
2. 2
   workup.STIRRINGwas stirred for 1 h at 20-25° C
3. 3
   SonstigeThe two layers were separated
4. 4
   Waschenthe organic layer was washed with 0.1 l of water
5. 5
   EinengenThe organic layer was concentrated at 40° C. to dryness under vacuum
6. 6
   workup.ADDITION100 ml of ethanol and 900 ml of n-hexane were then added
7. 7
   Temperaturthe mixture was heated to 55-60° C.
8. 8
   workup.DISSOLUTIONto dissolve (the solution
9. 9
   workup.ADDITION5 wt % of 2S activated charcoal and 5 wt % of Clarcel® were added to the mixture which
10. 10
    Temperaturwas maintained 30 minutes at 55-60° C
11. 11
    FiltrationThe Clarcel® and the charcoal were then filtered at 55-60° C.
12. 12
    Waschenwashed twice with 0.1 l of ethanol
13. 13
    SonstigeThe ethanol was then partially removed by distillation under vacuum at 40±5° C
14. 14
    TemperaturThe mixture was cooled to 20° C.
15. 15
    Temperaturto 0-5° C. and maintained 1 hour at this temperature
16. 16
    FiltrationThe suspension was filtered
17. 17
    Waschenthe cake was washed twice with 0.1 l of n-hexane at 0-5° C
18. 18
    TrocknenThe wet abiraterone acetate was dried at 50° C. under vacuum

Vorschrift

1 l of THF was added to 100 g (0.286 mole) of abiraterone. 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 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 (0.229 mole) of the pure abiraterone acetate (up to 99.0% by HPLC). The yield from abiraterone was around 90%. The overall yield from DHEA was around 43% by weight.

Quelle