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Synthesis method of 17alpha-hydroxyl progesterone

The technology of a hydroxyprogesterone and a synthetic method, which is applied in the field of synthesis of steroid hormone drugs, can solve problems such as limited application, and achieve the effects of low raw material cost, mild reaction conditions, and easy industrial implementation

Inactive Publication Date: 2014-07-09
ZHEJIANG PURUI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Among them, compound (5) is the product of configuration inversion during the addition process, which limits its application in industrial production

Method used

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  • Synthesis method of 17alpha-hydroxyl progesterone
  • Synthesis method of 17alpha-hydroxyl progesterone
  • Synthesis method of 17alpha-hydroxyl progesterone

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Experimental program
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preparation example Construction

[0028] The synthetic method of 17α-hydroxyprogesterone of the present invention, with easy-to-obtain, cheap 4-androstene-dione as starting material, through liquid reagent acetone cyanohydrin cyanation, with triethyl orthoformate and ethanol protection 3 The carbonyl group is protected by vinyl butyl ether at the 17th hydroxyl group. After the Grignard reaction, it is hydrolyzed to generate important raw materials and key intermediates for the synthesis of steroid hormone drugs such as medroxyprogesterone, prednisolone, and dexamethasone. The 17α-hydroxyprogesterone; Specifically comprise the following steps:

[0029] The first step, cyanation: add acetone cyanohydrin to the weak alkaline mixed solution of 4-androstene-dione and methanol (such as sodium carbonate, potassium carbonate, sodium hydroxide), and use acetone cyanohydrin to 4-androstene The carbonyl of ene-dione (I) is cyanated to generate compound 17α-hydroxy-17β-cyanoandrost-4-en-3-one (II);

[0030]

[0031] I...

Embodiment 1

[0043] Synthesis of compound (II)

[0044] Add 30 grams of 4-androstene-dione, 100 milliliters of methanol, 35 milliliters of acetone cyanohydrin, and 20 milliliters of 2.2% sodium carbonate solution into 250 milliliters of three-necked reaction flask equipped with mechanical stirring and a thermometer, and react at 50°C for 28 hours. The reaction was monitored by thin-layer analysis; after the reaction, it was added to 300 ml of ice water, stirred for 0.5 hours, filtered with suction, washed with water until neutral, and dried at 65°C to obtain 30.9 g of the product, with a yield of 103%.

Embodiment 2

[0046] Synthesis of compound (II)

[0047] Add 30 grams of 4-androstene-dione, 100 milliliters of methanol, 35 milliliters of acetone cyanohydrin, and 20 milliliters of 2.2% potassium carbonate solution into 250 milliliters of three-necked reaction flask equipped with mechanical stirring and a thermometer, and react for 28 hours at 50°C. The reaction was monitored by thin-layer analysis; after the reaction, it was added to 300 ml of ice water, stirred for 0.5 hours, filtered with suction, washed with water until neutral, and dried at 65°C to obtain 31.2 g of the product, with a yield of 104%.

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Abstract

The invention discloses a synthesis method of 17alpha-hydroxyl progesterone, which comprises the steps of by taking 4-androstene-diketone as a starting raw material, carrying out vyanation via acetone cyanohydrin, protecting 3carbonyl by using triethyl orthoformate and ethyl alcohol, protecting 17hydroxy by using butyl vinyl ether, and carrying out hydrolysis after Grignard reaction to generate the 17alpha-hydroxyl progesterone. According to the synthesis method, the cost is reduced, the environment pollution is decreased, the reaction time is shortened, the aftertreatment process of the industrial production is simplified, the production time and cost are greatly saved, the productivity is improved and convenience is brought to the industrial implementation. Compared with the traditional process, the synthesis method has the characteristics of low raw material cost, simple and convenient method, high yield, good selectivity, mild reaction condition, small pollution and applicability to industrial production; and the method is stable and easy to realize.

Description

technical field [0001] The invention relates to a method for synthesizing steroid hormone drugs, in particular to a method for synthesizing 17α-hydroxy progesterone. Background technique [0002] 17α-Hydroxyprogesterone (C21H30O3) is a C-21 endogenous progesterone produced during the synthesis of glucocorticoids and sex steroids, which can be converted from progesterone under the action of 17α-hydroxylase, or in 3β- Under the action of hydroxysteroid dehydrogenase (3β-HSD), it is converted from 17α-hydroxypregnenolone, mainly produced in the adrenal cortex, and partially produced in the gonads. [0003] At present, 17α-hydroxyprogesterone is mainly made of diosgenin, sisal saponin and saponin, and undergoes reactions such as ring opening, acetylation, oxidation, hydrolysis, epoxidation, oxidation, addition, and catalytic hydrogenation. to prepare. This preparation method has the disadvantages of serious environmental pollution, cumbersome synthesis steps, dangerous reactio...

Claims

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Application Information

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IPC IPC(8): C07J7/00
Inventor 徐润星张学忠
Owner ZHEJIANG PURUI PHARMA
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