A kind of refined decolorization method of finasteride

Abstract

The invention provides a refined decolorization method of finasteride. It uses a mixed solution of sodium borohydride and reducing sulfate to convert DDQ (dichlorodicyanobenzoquinone) remaining in the finasteride dehydrogenation step into its reduced state DDHQ (dichlorodicyanohydroquinone), Finally, it is converted into salt and removed under alkaline conditions, avoiding the need for repeated solvent refining or column decolorization in the traditional process, and greatly improving the product yield and production efficiency. The finasteride obtained through this method is a white solid. The yield can reach 93%, and the quality meets the latest pharmacopoeia standard.

Description

technical field [0001] The invention belongs to the field of organic chemistry, and in particular relates to a method for refining and decolorizing finasteride. Background technique [0002] Finasteride is a steroid drug developed by Merck and mainly used for the treatment of benign prostatic hyperplasia. Its representative preparation is named Proscar (Proscar). Dehydrogenation of the intermediate N-tert-butyl-3-oxo-4-aza-5α-androst-17β-carboxamide (dihydroposcar): [0003] [0004] The dehydrogenation methods reported in the literature include: 1) iodine deiodination method; 2) selenium reagent dehydrogenation method; 3) DDQ (dichlorodicyanobenzoquinone) dehydrogenation method. Among them, the DDQ dehydrogenation process is the most widely used dehydrogenation process because of its good selectivity and less impurities. This process generally uses toluene or dioxane as a solvent, and BSTFA as a reaction aid. At the reflux temperature, DDQ can be selected It dehydrogen...

AI Technical Summary

Problems solved by technology

[0006] During production, in order to ensure the complete reaction, the amount of DDQ will generally be a little more than the theoretical value, so after the reaction is over, there will be a small amount of DDQ remaining in the system, and the quinone structure of DDQ itself limits its structure that cannot be converted into a salt , so it is difficult to remove it by alkaline water washing

It is these small amounts of residual DDQ that make finasteride yellow, which cannot meet the white to off-white color standard in the Pharmacopoeia, and ordinary activated carbon and other adsorption and decolorization methods have basically no effect on it. In production, repeated solvent refining or The way of passing through the column is used to remove the color, so the final yield is not high. In order to meet the requirements of the Pharmacopoeia, the yield of the dehydrogenation step is generally only about 80%, and the yield loss caused by decolorization is relatively serious.

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