Preparation method of 1,6-didehydrogenation-17a-hydroxyl progesterone product

Abstract

The invention provides a preparation method of a 1,6-didehydrogenation-17a-hydroxyl progesterone product. The preparation method includes the steps that 1,4-androstenedione (IDD) is adopted as a raw material, firstly, IDD molecules and acetone cyanohydrin react in a first organic solvent under the catalyzation of alkali, so that a hydroxyl-cyanogen product is obtained; then the hydroxyl-cyanogen product is prepared into 1,6-didehydrogenation-17a-hydroxyl progesterone under the existence of methyl magnesium halide, a second organic solvent and acid; then 1,6-didehydrogenation-17a-hydroxyl progesterone is subjected to heating reflux and decoloration in methylbenzene, acetone or lower alcohol of C4 or below and recrystallized, so that the1,6-didehydrogenation-17a-hydroxyl progesterone productis obtained. With the IDD being the raw material, compared with the traditional production method that dioscin is used as a raw material, the preparation method has the advantages of being wide in source of the raw material, making the technology economic and environmentally friendly and lowering production costs substantially. In the preparation method, expensive and toxic DDQ and a chloranil dehydrogenating agent do not need to be used; the solvent used in the technology can be recycled and applied mechanically, economy and environmental protection are realized, and industrialized production is quite easy.

Description

technical field [0001] The invention belongs to the preparation technology of steroid hormone drug intermediates, and specifically relates to a preparation method of 1,6-didehydro-17a-hydroxyprogesterone product. Background technique [0002] Cyproterone acetate, referred to as CPA, commonly known as cyproterone, the chemical name is 6-chloro-1.2a-methine-17a-hydroxy-pregna-1,4-diene-3,20-di Ketone-17-acetate is a kind of progestin drug, which is mainly used clinically for female contraception, female acne, and the treatment of hirsutism and alopecia caused by excessive male androgen secretion, and is also used for male benign The treatment of diseases such as prostatic hypertrophy and early prostate cancer has a huge market. The production method of CPA is to extract diosgenin from the yam plant, and obtain the key intermediate 17a-hydroxyl by 8-step reactions such as protection, oxidation, cracking, elimination, epoxidation, austenitic oxidation, bromination, and debromin...

AI Technical Summary

Problems solved by technology

The 1,6-didehydro-17a-hydroxyprogesterone production process uses relatively expensive and toxic DDQ and chloranil dehydrogenation agents to dehydrogenate the 1-position and 6-position of the 17a-hydroxyprogesterone molecule respectively, The quality of the product obtained after each step of reaction treatment is poor, and all need to be treated with a large amount of alkaline water, resulting in more waste water, which is not easy to handle and easily pollutes the environment; the production process is complicated to operate, and the total yield of the two-step synthesis is less than 45%, and the production cost is high. More importantly, with the depletion of wild yam plant resources, and the artificial planting of yam plants, the production costs of saponin and dienes have doubled due to the increasing cost of labor and chemical fertilizers, resulting in 1,6- The production cost of didehydro-17a-hydroxyprogesterone has further increased, resulting in an increase in the production cost of CPA

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