Method for synthesizing 9beta,10alpha-dehydroprogesterone ketal through photochemical isomerization in micro-channel reactor

Abstract

The invention relates to a method for synthesizing 9beta,10alpha-dehydroprogesterone ketal through photochemical isomerization in a micro-channel reactor. The method comprises the following steps: dissolving a raw material, namely 9alpha,10beta-dehydroprogesterone ketal in a medium polar solvent to prepare a solution with the concentration of 10-50 g / ml, adding an antioxidant and organic alkali into the solution, and carrying out uniform stirring and mixing to prepare a photochemical reaction solution; and introducing nitrogen is into the obtained photochemical reaction solution for protection, and conducting illumination three times so as to realize photoisomerization of 9alpha,10 beta-dehydroprogesterone ketal. According to the invention, reaction time is greatly shortened, generation ofphotoisomerization reaction by-products is inhibited, conversion rate is high, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemical synthesis, in particular to a method for photochemically synthesizing 9β, 10α-dehydroprogesterone ketal with a microchannel reactor. Background technique [0002] Dehydroprogesterone is a synthetic progestin. Compared with the natural hormone progesterone, dehydroprogesterone has a trans configuration, so this type of drug is extremely stable during digestion, absorption and metabolism, and has very high oral activity. In addition, dehydroprogesterone drugs do not have the side effects of hormones such as androgen, estrogen, and corticosteroids, and are currently the most ideal progesterone drugs. Once this type of progesterone drug came out, it attracted the attention of drug researchers worldwide, and its synthesis method has also become a hot spot for chemical workers. [0003] In the synthetic route of progesterone, there are many reports on the step of photochemically synthesizing 9β, 10α-de...

AI Technical Summary

Problems solved by technology

[0003] In the synthetic route of progesterone, there are many reports on the step of photochemically synthesizing 9β, 10α-dehydroprogesterone ketal with the intermediate 9α, 10β-dehydroprogesterone ketal as raw material. The main problem lies in the requirement of light for this step Extremely harsh, the coexistence of multiple reversible reactions causes the main product to be easily converted into by-products; and 9α, 10β-dehydroprogesterone ketal produces a large number of intermediates during the ring-opening process, and only by accurately controlling the ring-closing process can more 9β be obtained , 10α-Dehydroprogesterone Ketal

In this regard, people usually use two-stage reaction conditions, and use different wavelengths to open the ring to obtain intermediates and intermediates. , 10α-dehydroprogesterone ketal, obtained a higher yield (75.5%, based on the consumption of raw materials), but there are still some raw materials left, can not react completely

Chinese patent CN102558272B adopts an internal immersion upward bubbling double-filter system for photochemical reaction. This method has a complicated operating system, unstable light, and the conversion rate of photoalteration reaction is between 20% and 25%, which increases the by-products in the reaction process. , so using this method to synthesize 9β, 10α-dehydroprogesterone ketal has limited application range and poor universality

However, there is a fatal defect in the traditional tank-type photochemical reactor, that is, the mass and heat transfer efficiency of the photoisomerization reaction in the tank-type photochemical reactor is low. The photoreaction solution is not illuminated enough, which leads to uneven photoreaction, and a wide variety of by-products still inevitably appear in the product at the end of the reaction

Images