Preparation method for canrenone

Abstract

The invention discloses a preparation method for canrenone. According to the preparation method, canrenone is obtained through an etherification reaction and a dehydrogenation reaction, wherein 17 beta-hydroxyl-4-alkene-3-ketone-17 alpha-pregnene-21-carboxylic acid-gamma-lactone is taken as a raw material; under the presence of a catalyst, the etherification reaction is carried out between 17 beta-hydroxyl-4-alkene-3-ketone-17 alpha-pregnene-21-carboxylic acid-gamma-lactone and triethyl orthoformate to generate 17 beta-hydroxyl-3,5-diene-3-ethoxy-17 alpha-pregnene-21-carboxylic acid-gamma-lactone; the catalyst is pyridine hydrobromide or pyridinium hydrochloride; under the presence of an organic solvent, the dehydrogenation reaction is carried out between an etherification reaction product and an oxidant to generate canrenone; the oxidant is tetrachloro-p-benzoquinone, tetrachloro-o-benzoquinone or 2,3-dichloro-5,6-dicyano-p-benzoquinone. Through the adoption of the preparation method, canrenone of which the purity is 99% or higher can be eventually obtained, and the total weight yield can reach 90% or higher. Therefore, the preparation method is suitable for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a preparation method of canrenone. Background technique [0002] Canrenone, whose chemical name is 17β-hydroxy-3-oxo-17α-pregna-4,6-diene-21-carboxylate-γ-lactone, is a commonly used diuretic and is also a synthetic Important intermediates of prinone, drospirenone, spironolactone, etc. [0003] Chinese patent document CN104327150A discloses a method for synthesizing canrenone, an intermediate of spironolactone, which uses 4AD as a raw material, and sequentially undergoes acetylenation reaction, hydrogenation reaction, oxidative cyclization reaction, and bromo-debromination reaction to prepare canrenone , wherein, the method for preparing canrenone from 17β-hydroxy-4-en-3-one-17α-pregna-21-carboxylic acid-γ-lactone (compound IV) is to make compound IV and The bromination reagent reacts to form a 6-bromo-3-one structure, and then heats up to 90-110°C in an alka...

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Problems solved by technology

[0003] Chinese patent document CN104327150A discloses a method for synthesizing canrenone, an intermediate of spironolactone, which uses 4AD as a raw material, and sequentially undergoes acetylenation reaction, hydrogenation reaction, oxidative cyclization reaction, and bromo-debromination reaction to prepare canrenone , wherein, the method for preparing canrenone from 17β-hydroxy-4-en-3-one-17α-pregna-21-carboxylic acid-γ-lactone (compound IV) is to make compound IV and The bromination reagent reacts to form a 6-bromo-3-one structure, and then heats up to 90-110°C in an alkaline environment to debrominate to obtain canrenone; the disadvantage of this reaction is that the debromination reaction under alkaline conditions will lead to Lactone is hydrolyzed and ring-opened, therefore, the weight yield of this reaction is only 78%, and the product purity after refining also only has 98.5%, thus is not suitable for industrialized large-scale production