A kind of method for preparing spironolactone

A technology of spironolactone and lactone, which is applied in the field of preparation of spironolactone, can solve the problems of harsh reaction conditions, high production cost, long reaction route, etc., and achieve the effect of short synthesis route, high total yield and cheap reagents

Active Publication Date: 2019-04-23
HUAIHAI INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] The technical problem to be solved by the present invention is to overcome the defects of harsh reaction conditions, long reaction route, high production cost and complicated operation in the technology reported by the existing preparation formula (I) compound spironolactone, and provide a simple and effective preparation formula (I) The method for compound spironolactone, the method has mild reaction conditions, short reaction route and simple operation

Method used

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  • A kind of method for preparing spironolactone
  • A kind of method for preparing spironolactone
  • A kind of method for preparing spironolactone

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Embodiment 1

[0024] Embodiment 1 Preparation of formula (III) compound 17β-hydroxyl-3-ethoxy-17α-pregna-3,5-diene-21-carboxylic acid-γ-lactone

[0025] Under nitrogen protection, 20mmol formula (II) compound 3-ethoxy-androst-3,5-dien-17-one, 24mmol acrolein, 24mmol lithium bromide, 1.2mmol tetrahydropyridotriazole carbene salt Catalyst (R 1 =R 2 =CH 3 , R 3 =Cl) and 2 mmol triethylamine were added to a strictly dry reaction flask, then 20 mL of absolutely anhydrous dichloroethane was injected into the reaction flask, the stopper was sealed, and the reaction was stirred at room temperature for 5 h, then the stirring was stopped, and 20 mL of water was added to the reaction flask. , and then stirred for 1 h; filtered, the organic layer was separated, the aqueous layer was washed twice with dichloroethane, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a white solid with a yield of 89%.

Embodiment 2

[0026] Example 2 Preparation of compound 17β-hydroxyl-3-ethoxyl-17α-pregna-3,5-diene-21-carboxylic acid-γ-lactone of formula (III) Under nitrogen protection, 20mmol of formula ( II) compound 3-ethoxy-androst-3,5-dien-17-one, 24mmol acrolein, 24mmol lithium chloride, 1.5mmol tetrahydropyridotriazole carbene salt (R 1 =CH 3 , R 2 =R 3 =OCH 3 ) and 3mmol potassium carbonate were added to a strictly dry reaction flask, then 20mL of absolutely anhydrous toluene was injected into the reaction flask, the stopper was sealed, the reaction was stirred at room temperature for 6h, the stirring was stopped, 20mL of water was added, and the reaction was stirred for 1h; After filtration, the organic layer was separated, the aqueous layer was washed twice with toluene, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a white solid with a yield of 78%.

Embodiment 3

[0027] Embodiment 3 Preparation of formula (III) compound 17β-hydroxyl-3-ethoxyl-17α-pregna-3,5-diene-21-carboxylic acid-γ-lactone

[0028] Under nitrogen protection, 20mmol formula (II) compound 3-ethoxy-androst-3,5-dien-17-one, 24mmol acrolein, 24mmol potassium bromide, 1.4mmol tetrahydropyridotriazole Carbene salt catalyst (R 1 =R 2 =CH 2 Cl, R 3 =H) and 3.4mmol sodium acetate were added to a strictly dry reaction flask, and then 20mL of absolutely anhydrous dichloroethane was injected into the reaction flask, the stopper was sealed, and the reaction was stirred at room temperature for 6h, then the stirring was stopped, and 20mL of water was added to the reaction flask. , and stirred for another 1 h; filtered, the organic layer was separated, the aqueous layer was washed twice with dichloroethane, the organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a white solid, yield: 84%.

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Abstract

The invention discloses a method for preparing spirolactone. The method comprises the following steps: 1, performing a reaction on a compound shown as a formula (II) and acrolein under the action of a catalyst, alkali and Lewis acid to obtain a compound shown as a formula (III); 2, performing a reaction on the compound shown as the formula (III) and chloranil to obtain a compound shown as a formula (IV); 3, performing an addition reaction on the compound shown as the formula (IV) and thioacetic acid to obtain the spirolactone. The preparation method of the spirolactone, provided by the invention, has the advantages of a short synthetic route, cheapness and easy obtainment of used reagents, simple operation, high total yield rate, and suitability for industrial production; a novel way for preparing the spirolactone is provided.

Description

technical field [0001] The invention belongs to the technical field of organic preparation, and in particular relates to a preparation method of spironolactone. Background technique [0002] Spironolactone (Formula I), chemically named (7α, 17α)-7-(acetylmercapto)-17-hydroxyl-3-oxopregna-4-ene-21-carboxylic acid-γ-lactone, is manufactured by Pfizer The mineralocorticoid antagonist developed by the company is now on the market in many countries. It is mainly used for the diagnosis and treatment of primary aldosteronism, and also for the treatment of hypertension and the prevention of hypokalemia. [0003] [0004] Existing at present about the report of formula (I) compound spironolactone preparation technology, mainly be divided into two classes: one kind is to take dehydroepiandrosterone as raw material, through addition, Grignard reaction, carbon dioxide carboxylation, reduction, lactonization After the reaction to obtain a five-membered spiro ring, it can be obtained ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J71/00
CPCC07J71/0005
Inventor 王启发程青芳王玉枝陈少平
Owner HUAIHAI INST OF TECH
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