Preparation method of 1,4-dipregnene-16-beta-methyl-17-alpha-21-bihydroxy object

Abstract

The present invention relates to a preparation method of 1,4-pregnanediene-16beta-methyl-17alpha, 21-dihydroxyl compound. Said preparation method includes the following steps: (1), using 1,4,16-pregnanetriene compound, catalyst, trimethylchlorosilane, Grignard reapent and hexamethyl phosphoric triamide according to a certain weight ratio and making them produce Grignard reaction in ether solvent, its reaction temperature is-50-10deg.C, reaction time is 3-15 hr, so as to obtain Grignard compound; and (2), utilizing said Grignard compound, alkali and m-chlorobenzo-hydroperoxide according to a certain weight ratio and making them produce reaction in a salvent, its reaction temperature is-30-5deg.C and reaction time is 1-5 h; using acid to regulate solution pH value to 1-4 so as to obtain the invented product 1,4-pregnanediene-16 beta-methyl-17alpha, 21-dihydroxyl compound.

Description

technical field

[0001] The invention relates to a preparation method of 1,4-pregnane-16β-methyl-17α,21-dihydroxy. Background technique

[0002] 16β-methyl adrenocorticosteroids such as beclomethasone dipropionate and betamethasone have been relatively stable in the drug market at home and abroad, and have high profit margins. However, the current domestic traditional 16β-methyl introduction methods mainly Grignard reagents are used to break α-epoxy, but this method needs to protect 3,20-diketone, and also produces 17α-methyl by-products, the process is complicated, and the separation of products and by-products is difficult, which also brings Many inconveniences; in addition, the introduction of 16β-methyl increases the steric hindrance of introducing acetate at the 21st position, and the total yield is less than 60%. It also brings great difficulty to the 1,2-position dehydrogenation process. Therefore, it is of great significance to study a process method with strong spec...

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