Acetic Anhydride → Abiraterone Acetate

関与物質

反応条件

反応手順

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.

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