Preparation method for canrenone

A technology of canrenone and hydroxyl, applied in the field of drug synthesis, can solve the problems that the weight yield is only 78%, it is not suitable for large-scale industrial production, and the product purity is only 98.5%.

Inactive Publication Date: 2015-11-11
JIANGSU JIAERKE PHARMA GRP CORP
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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

Method used

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Examples

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Embodiment 1）

[0023] The preparation method of canrenone in this embodiment has the following steps:

[0024] ①Etherification reaction: pump 26kg of anhydrous tetrahydrofuran into a 100L glass-lined reactor, then pump in 12kg of triethyl orthoformate (0.081mol), and then add 15kg of 17β-hydroxy-4-ene-3- Keto-17α-pregna-21-carboxylic acid-γ-lactone (0.044mol) and 0.2kg of pyridine hydrobromide were heated to 58°C and stirred for 2.5h.

[0025] After the reaction, cool down to 0°C, add 0.2L triethylamine, stir for 15 minutes, centrifuge, wash, and dry to obtain the ether compound 17β-hydroxy-3,5-diene-3-ethoxy-17α-pregna- 21-Carboxylic acid-γ-lactone 15.5kg.

[0026] ②Dehydrogenation reaction: pump 82.5kg of dichloromethane into a 400L glass-lined reactor, then pump in 30kg of methanol, 16.4kg of water, the ether compound (0.042mol) obtained in step ① and 10.6kg of para Chlorobenzoquinone (0.043mol), stirred at room temperature for 1 hour, then added 47 kg of 10 wt% sodium thiosulfate solut...

Embodiment 2～ Embodiment 3）

[0031] Each embodiment is basically the same as embodiment 1, the difference lies in the type of oxidant, see Table 1 for details.

[0032]

Embodiment 4）

[0034] This example is basically the same as Example 1, except for the type of catalyst, see Table 2 for details.

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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...

Claims

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Application Information

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IPC IPC(8): C07J21/00
CPCC07J21/003
Inventor 蒋澄宇顾向忠汤志伟
Owner JIANGSU JIAERKE PHARMA GRP CORP
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