Method for Preparing Abiraterone Acetate

摘要

A method for preparing abiraterone acetate. The steps are: dehydroepiandrosterone acetate and trifluoromethanesulphonic anhydride undergo a sulfonylation reaction under the catalysis of an organic base to obtain a compound as represented by formula II; the compound is reacted with a 3-pyridine organoboron compound or a 3-pyridine organosilicone compound under the catalysis of Bis(triphenylphosphine) palladium(II) dichloride to obtain a crude abiraterone acetate product; the crude product is recrystallized in a protic or aprotic solvent to obtain an abiraterone acetate crystal; the crystal is further put into a solvent which easily dissolves the crystal and dissolved under heating, and the solution is dropwise added into a solvent which does not easily dissolve the crystal until a solid is precipitated under stirring, such that a micro powder abiraterone acetate is obtained; and the solvent which easily dissolves the crystal is a mixture of any two or more of acetone, ethanol and water, and the solvent which does not easily dissolve the crystal is water. The method has a rational route, a simple and convenient operation, a good product quality, and a high yield. No column chromatography, and salt-formation are required in the entire process to satisfy requirements of industrial scale productions. Furthermore, an abiraterone acetate particle size of about 10 um is obtained.

主权项

1. A method for preparing abiraterone acetate, comprises the following steps:
(1) Dehydroepiandrosterone acetate reacting with Trifluoromethanesulfonic anhydride in the presence of organic base as catalyst at −30˜50° C. for 1-72 hours to obtain a compound as shown in Formula II ; (2) the compound of Formula II reacting with 3-pyridine organoboron compound or 3-pyridine organosilicon compound in the presence of Bis(triphenylphosphine) palladium(II) dichloride as catalyst at 5˜150° C. for 1-72 hours to obtain crude abiraterone acetate; (3) the crude abiraterone acetate recrystallizing in proton or non-proton solvent, in the mass-volume ratio of crude abiraterone acetate to proton or non-proton solvent is 1:10-30 at 10˜30° C. to obtain abiraterone acetate crystal; and (4) putting abiraterone acetate crystals into soluble solvent and heating to dissolve, then dripping it to insoluble solvent, controlling the stirring speed, temperature and amount of solvent, to precipitate solids to obtain micronized abiraterone acetate; said soluble solvent is a mixture of any two or more of acetone, ethanol and water; said insoluble solvent is water.