Method for synthesizing drospirenone

Abstract

The invention relates to a method for synthesizing drospirenone and belongs to the field of pharmaceutical chemicals, which comprises: reacting a 3beta,5beta-dyhydroxy-6beta,7beta,15beta,16beta-imethylene-17alpha-(3'-hydroxypropyl)-androstene-17ol compound serving as a raw material in dichloromethane in the presence of dichlorodimethylhydantoin, potassium bicarbonate and crown ether, which serve as catalysts, to obtain an 3-oxo-5beta-hydroxy-6beta, 7beta,15beta,16beta-dimethylene-17alpha(spiro)butyrolactone intermediate; removing excessive oxidant by using a small amount of sodium sulfite, filtering the solution, adding a certain amount of phosphorus pentoxide into solution of dichloromethane for dehydration, adding water for washing the reaction product for one time at the end ( detected by thin-layer chromatography) of the reaction and washing the reaction product for one time with saturated solution of sodium bicarbonate; drying the reaction product with anhydrous sodium sulfate, filtering the reaction product, distilling and recovering solvent and crystallizing the solid with water solution (in a volume ratio of 3:1) of methanol; and finally, recrystallizing the obtained solid with isopropylacetate to obtain a qualified drospirenone product. The synthesis yield of the method is about 67 percent. The reaction is mild and easy to operate and consumes a small amount of organic solvent.

Description

technical field [0001] The invention relates to a synthesis method of drospirenone, which belongs to the field of medicine and chemical industry. Background technique [0002] Drospirenone is a kind of important contraceptive, and existing drospirenone synthetic method, uses sodium hypochlorite to add TEMPO (2,2,6,6-tetramethylpiperidine nitroxide free radical) mostly in synthetic technology to carry out Catalytic oxidation, in the reaction process, is prone to overreaction, the reaction process is not peaceful, and more chlorinated by-products are produced, which is relatively polluting to the environment. Moreover, it is necessary to carry out stratified treatment of water and organic solvents in production, which will also cause a large amount of loss of organic solvents and generate more sewage. In addition, the transportation and storage of hypohalite such as oxidant sodium hypochlorite is not very convenient, and it is easy to decompose and fail. [0003] The inventi...

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Problems solved by technology

[0002] Drospirenone is a kind of important contraceptive, and existing drospirenone synthetic method, uses sodium hypochlorite to add TEMPO (2,2,6,6-tetramethylpiperidine nitroxide free radical) mostly in synthetic technology to carry out Catalytic oxidation, in the reaction process, it is easy to overreact, the reaction process is not peaceful, and more chlorinated by-products are produced, which is relatively harmful to the environment

Moreover, it is necessary to carry out stratified treatment of water and organic solvents in production, which will also cause a large amount of loss of organic solvents and produce more sewage

In addition, the transportation and storage of hypohalite such as oxidant sodium hypochlorite is not very convenient, and it is easy to decompose and fail

[0003] The invention patent application with the patent application number 200610027940.5 discloses a method for synthesizing drospirenone, which uses 3β, 5-dihydroxy-6β, 7β, 15β, 16β-dimethylene-5β-androst-17-one As a raw material, epoxy is introduced at the 17th position, and then drospirenone is obtained through condensation, dehydroxylation and oxidation. This synthetic method also has the disadvantages of large consumption of organic solvent, relatively large pollution, complicated operation, and high cost. low yield