Improved synthesis method of 3beta-hydroxy-16alpha, 17alpha-epxoy-5-pregnenolone-20-ketone

Abstract

The invention discloses an improved synthesis method of 3beta-hydroxy-16alpha, 17alpha-epxoy-5-pregnenolone-20-ketone (hereinafter referred to epoxy prognenolone). The improved synthesis method comprises the following steps of: putting dehydropregnenolone acetate to a mixed solvent, controlling temperature, respectively and sequentially dropwise adding hydrogen peroxide, alkaline water, hydrogen peroxide and alkaline water, after heat preservation reaction is ended, cooling, centrifuging, circularly applying mother liquid, washing filter cakes till the filter cakes are neutral, and drying to obtain an epoxy prognenolone product; and after using the mother liquid for enough times, dropwise adding a quenching reagent, and preprocessing to obtain the epoxy prognenolone product. According to the improved synthesis method, the dosage and consumption of the solvent are substantially reduced, the distillation process of the solvent is substantially shortened, the lot production capacity of a reaction kettle is substantially improved, and the content of the obtained epoxy prognenolone is above 99.0%. The improved synthesis method has the advantages of low production cost, high production safety and material stability and is suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to a synthesis method of steroidal compounds, in particular to an improved synthesis method of 3β-hydroxyl-16α, 17α-epoxy-5-pregnene-20-one. [0002] Background technique [0003] 3β-Hydroxy-16α, 17α-epoxy-5-pregnene-20-one (abbreviated as oxygen bridge in the steroid hormone industry) is the pre-intermediate for the production of Woshi oxide, and Woshi oxide is the production Important intermediates of steroidal drugs such as hydrocortisone, dexamethasone, prednisone acetate, and megestrol, and the quality of 3β-hydroxy-16α, 17α-epoxy-5-pregnene-20-one is directly It determines the yield and quality of Woshi oxide. [0004] At present, the process commonly used in China is that the ratio of raw materials is 1.0 parts by weight of dienolone acetate, 10.0 to 12.5 parts by volume of methanol, 0.8 to 0.9 parts by weight of 30% hydrogen peroxide, and react under alkaline conditions for about 36 hours to distill the methanol...

AI Technical Summary

Problems solved by technology

However, due to the excessive proportion of methanol used in this process, only about 10kg of dienolone acetate can be put into a 1000L reactor when applied to industrial production, and the operation of distilling and recovering methanol is required for each batch; the hydrogen peroxide and diene The molar ratio of alcohol ketone acetate is as high as 41:1, which not only causes waste, but also causes the concentration of peroxide to become higher and higher in the post-treatment distillation process, especially in the later stage of concentration, resulting in an explosion accident; The bridge is not stable enough, and it is easy to deteriorate if it continues to distill when most of the solvent is evaporated

The reason is that the temperature in the later stage of concentration is high, and the concentration of peroxide in the system is too high, which destroys the structure of the oxygen bridge.

This process directly distills and concentrates the peroxide in the system without quenching the reaction, which increases the possibility of bad material accidents in production