Preparation method of dehydroepiandrosterone acetate

Abstract

The invention provides a preparation method of dehydroepiandrosterone acetate, which comprises the following steps: firstly, mixing hydroxylamine hydrochloride and pyridine to obtain a hydroxylamine hydrochloride solution, mixing dehydropregnenolone acetate and pyridine to obtain a dehydropregnenolone acetate solution, respectively pumping the hydroxylamine hydrochloride solution and the dehydropregnenolone acetate solution into an oximation micro-channel reactor, and carrying out oximation reaction to obtain dehydroepiandrosterone acetate. Pumping the oximation reaction liquid into a rearrangement micro-channel reactor, carrying out a rearrangement reaction to obtain a rearrangement reaction liquid, pumping the rearrangement reaction liquid and hydrochloric acid into a hydrolysis micro-channel reactor, carrying out a hydrolysis reaction to obtain a hydrolysis reaction liquid, and extracting the hydrolysis reaction liquid by using an extraction solvent, and drying the extraction solvent to obtain the dehydroepiandrosterone acetate. The preparation method disclosed by the invention is simple in process, free of unit operation of an intermediate product, efficient and continuous, and has a good application prospect.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical intermediate production technology, in particular to a preparation method of dehydroepiandrosterone acetate. Background technique [0002] Dehydroepiandrosterone acetate is an important intermediate for the synthesis of various hormones, family planning products and other steroid hormone drugs, and it is used to synthesize testosterone, methyltestosterone, estradiol, estriol, etc. [0003] The method for synthesizing dehydroepiandrosterone acetate in the existing technology is mainly to use diene as raw material, and diene is also acetic acid pregnant dienolone, through oximation reaction, Beckmann rearrangement, hydrolysis, finally obtains dehydroepiandrosterone acetate Androsterone, in the prior art, in order to realize the control of impurities and yield, avoid the influence of solvents, raw materials and products added in the physical and chemical reaction process on Beckmann rearrangem...

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Problems solved by technology

[0003] The method for synthesizing dehydroepiandrosterone acetate in the existing technology is mainly to use diene as raw material, and diene is also acetic acid pregnant dienolone, through oximation reaction, Beckmann rearrangement, hydrolysis, finally obtains dehydroepiandrosterone acetate Androsterone, in the prior art, in order to realize the control of impurities and yield, avoid the influence of solvents, raw materials and products added in the physical and chemical reaction process on Beckmann rearrangement, so the corresponding dry intermediates are produced in each step , and then re-feed the reaction again, which leads to the extension of the production cycle, and there are many reaction processes, and the amount of solvent and waste water generated in the middle greatly limits the efficient production

[0004] And because water can be produced in the reaction system and the selectivity of the existing preparation process to the solvent is high, it is difficult to realize the one-pot method. The Chinese patent CN103145784 of the prior art discloses a kind of production process close to the one-pot method. This process optimizes the solvent system of the reaction. In the production process, there is no need to produce dry intermediates, and the reaction liquid is directly used for material transfer and reproduction, which saves a large number of post-treatment operations of intermediates in the process, and the final yield reaches It is about 84%, far exceeding the production level of the existing technology, but it is inevitable in this process that the water generated by the oximation reaction needs to be controlled, so an intermediate filtration operation will be carried out, and the production process is only performed before the finished product is dried. Water washing and impurity removal operations are carried out, so the final product may have problems with high impurities

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