Method for preparing 17beta-carboxyl-4-androstene-3-ketone

A technology of androstene and carboxyl, which is applied in the field of preparation of 17β-carboxy-4-androstene-3-one, can solve the problems of low yield, high price, and difficult availability of raw materials, and achieve high yield and low price. Low cost, high yield effect

Inactive Publication Date: 2014-10-15
赵云现
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

The main defect of the above-mentioned synthetic method of 17β-carboxy-4-androsten-3-one is that the raw materials are n...

Method used

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  • Method for preparing 17beta-carboxyl-4-androstene-3-ketone
  • Method for preparing 17beta-carboxyl-4-androstene-3-ketone
  • Method for preparing 17beta-carboxyl-4-androstene-3-ketone

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preparation example Construction

[0024] The embodiment of the present invention discloses a preparation method of 17β-carboxy-4-androsten-3-one, which comprises the following steps:

[0025] a), under strong alkali conditions, 3-ethoxy-androst-3,5-dien-17-one and p-toluenesulfonylmethyl isonitrile react in an organic solvent to obtain formula (II) structure first intermediate product;

[0026]

[0027] b) The first intermediate is hydrolyzed under acidic conditions to obtain 17β-carboxy-4-androsten-3-one.

[0028] The preparation method of 17β-carboxy-4-androstene-3-one provided by the embodiment of the present invention is based on 3-ethoxyandrost-3,5-dien-17-one with lower cost and easier access to the market , first converting the 17-keto group of the starting material into a 17β-cyano group in one step (step a above), then converting the 17β-cyano group into a 17β-carboxyl group, and converting the 3-ethoxy group into a 3-keto group ( Step b) above.

[0029] The reaction principle of above-mentioned...

Embodiment 1

[0040] Example 1 Preparation of the first intermediate

[0041] Under the protection of nitrogen flow, 25g 3-ethoxy androst-3,5-dien-17-one and 45g potassium tert-butoxide were added to 1L ethylene glycol dimethyl ether and 300ml tert-butanol, and cooled to -5°C, add dropwise a solution made of 23.43g p-toluenesulfonylmethyl isonitrile and 140ml ethylene glycol dimethyl ether, after the dropwise addition is completed, return the temperature to room temperature, stir for 3h, and pour half-saturated chlorine In the sodium chloride aqueous solution, precipitates were precipitated, filtered, washed with water, and dried under reduced pressure to obtain 23.8 g of white crystals with a yield of 92%.

[0042] The proton nuclear magnetic resonance spectrum of product is as follows:

[0043] 1 H-NMR (CDCl 3 ) 0.95(s, 3H, 18-CH 3 )

[0044] 1.20(s, 3H, 19-CH 3 )

[0045] 5.71 (s, 1H, 4-H)

[0046] It can be seen that the first intermediate product prepared in this embodiment is ...

Embodiment 2

[0048] Embodiment two prepares the first intermediate

[0049] Under the protection of nitrogen flow, 25g 3-ethoxy androst-3,5-dien-17-one and 45g potassium tert-butoxide were added to 1L ethylene glycol dimethyl ether and 300ml tert-butanol, and cooled to -5°C, add dropwise a solution composed of 22g p-toluenesulfonylmethyl isonitrile and 140ml ethylene glycol dimethyl ether, after the dropwise addition is complete, return the temperature to room temperature, stir for 3h, pour into half-saturated chlorinated In the aqueous sodium solution, precipitates were precipitated, filtered, washed with water, and dried under reduced pressure to obtain 23.3 g of white crystals with a yield of 90%. The proton nuclear magnetic resonance spectrum of product is as follows:

[0050] 1 H-NMR (CDCl 3 )0.95(s, 3H, 18-CH 3 )

[0051] 1.20(s, 3H, 19-CH 3 )

[0052] 5.71 (s, 1H, 4-H)

[0053] It can be known that the first intermediate product prepared in this example is 3-ethoxy-17β-cyanoan...

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Abstract

The invention discloses a method for preparing 17beta-carboxyl-4-androstene-3-ketone. The method comprises a step (a) of enabling 3-ethoxy androstane-3,5-diene-17-ketone to react with tosylmethyl isocyanide in an organic solvent under the conditions of strong base, and obtaining a first intermediate product with a formula (II) structure; a step (b) of hydrolyzing the first intermediate product under the acidic conditions, and obtaining 17beta-carboxyl-4-androstene-3-ketone. The preparation method has the advantages of being low in cost and high in yield; and the formula (II) is as follows.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of 17β-carboxy-4-androsten-3-one. Background technique [0002] 17β-carboxy-4-androsten-3-one, whose structure is shown in formula (I), is a key intermediate for the synthesis of finasteride and dutasteride, the drugs for treating prostate. With the advent of population aging, the number of benign prostatic hyperplasia in the elderly increases, and the demand for prostatic drugs finasteride and dutasteride increases accordingly. As the intermediate of the above drugs, 17β-carboxy-4-androstene- The preparation of 3-keto has also attracted more and more attention. [0003] [0004] At present, the synthesis process of 17β-carboxy-4-androsten-3-one mainly includes the following methods: it is obtained by oxidation of progesterone through sodium hypochlorite; it is obtained by oxidation of 17β-formyl-4-androsten-3-one; 17β-hydroxymethyl-4-androsten...

Claims

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Application Information

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IPC IPC(8): C07J3/00
Inventor 赵云现李超余伟方明山
Owner 赵云现
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