Synthetic method of 17beta-cyano-17alpha-hydroxy-9-dehydroandrostenedione

A technology of hydroandrostenedione and synthesis method, which is applied in the synthesis field of 17β-cyano-17α-hydroxy-9-dehydroandrostenedione, can solve the problem of selectivity, poor repeatability, alkaline and acidic reagent dosage It is difficult to deal with problems such as large, cyanide-containing wastewater, etc., to achieve the effects of less online reaction, easy to achieve continuity, and high reuse rate.

Pending Publication Date: 2022-05-06
台州仙琚药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, the synthesis of 17β-cyano-17α-hydroxy-9-dehydroandrostenedione is mainly through dehydration reaction under acid catalysis and cyanation reaction under base catalysis, using 9-hydroxyandrostenedione as raw material. Realize (CN201410747239.5, CN201610204515.2, CN201811395764.X, CN201410707307.5 etc.); Adopt above-mentioned preparation 17β-cyano-17α-hydroxyl-9-dehydroandrostenedione, mainly have the following problems: (1) in Carried out under the traditional tank reaction conditions, the material backmixin

Method used

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  • Synthetic method of 17beta-cyano-17alpha-hydroxy-9-dehydroandrostenedione
  • Synthetic method of 17beta-cyano-17alpha-hydroxy-9-dehydroandrostenedione
  • Synthetic method of 17beta-cyano-17alpha-hydroxy-9-dehydroandrostenedione

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Dissolve 9-hydroxyandrost-4-ene-3,17-dione (10mmol, 3.02g) in 50mL ethanol and place in the first storage bottle A; dissolve acetone cyanohydrin (12mmol, 1.02g) in 15mL Ethanol is placed in the second storage bottle B, and the materials in the first storage bottle A and the second storage bottle B are transported into the mixer T through the first metering pump P1 and the second metering pump P2 respectively for mixing, and the mixed raw material liquid is continuously Enter the first tubular reactor R1 and carry out cyanation reaction (the inner diameter of the pipeline is 0.31cm, the length of the pipeline is 5m, and the strong basic ion exchange resin is filled in the pipeline 900 (OH), the same in the following examples), both ends are sealed with Floxacin, and the control of 9-hydroxy-androst-4-ene-3,17-dione: the molar flow ratio of acetone cyanohydrin is 1:1.2) , the temperature of the tubular reactor R1 is maintained at 70°C, and the residence time is 25min; af...

Embodiment 2

[0027] 9-Hydroxyandrost-4-ene-3,17-dione (20mmol, 6.04g) was dissolved in 100mL ethylene glycol and placed in the first storage bottle A; acetone cyanohydrin (22mmol, 1.87g) was dissolved Put 25mL of ethylene glycol in the second storage bottle B, the materials in the first storage bottle A and the second storage bottle B are transported through the first metering pump P1 and the second metering pump P2 respectively, and enter the mixer T for mixing , the mixed raw material solution enters the first tubular reactor R1 continuously to carry out the cyanation reaction (the inner diameter of the pipeline is 0.31cm, the length of the pipeline is 2m, the strong basic ion exchange resin is filled in the pipeline, the two ends are sealed with sandstar, and the control 9 The molar flow ratio of -hydroxyandrost-4-ene-3,17-dione: acetone cyanohydrin is 1:1.1), the temperature of the first tubular reactor R1 is maintained at 110° C., and the residence time is 15 minutes. The mixed raw ma...

Embodiment 3

[0029] Dissolve 9-hydroxyandrost-4-ene-3,17-dione (10mmol, 3.02g) in 50mL tetrahydrofuran and place in the first storage bottle A; dissolve acetone cyanohydrin (20mmol, 1.7g) in 20mL tetrahydrofuran and placed in the second storage bottle B. The materials in the first storage bottle A and the second storage bottle B are conveyed through the first metering pump P1 and the second metering pump P2 respectively, and then enter the mixer T for mixing, and the mixed raw material liquid continuously enters the first tubular reactor R1 for Cyanation reaction (the inner diameter of the pipeline is 0.31cm, the length of the pipeline is 3m, the pipeline is filled with strong basic ion exchange resin, both ends are sealed with sandstar, and the control of 9-hydroxyandrost-4-ene-3,17-dione : The molar flow ratio of acetone cyanohydrin is 1:2), the temperature of the first tubular reactor R1 is maintained at 50°C, and the residence time is 1h. The mixed raw material liquid enters the secon...

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Abstract

The invention discloses a synthesis method of 17 [beta]-cyano-17 [alpha]-hydroxy-9-dehydroandrostenedione, which comprises the following steps: (1) dissolving 9-hydroxyandrostane-4-ene-3, 17-dione and a cyaniding reagent in an organic solvent, and carrying out a cyanation reaction in a tubular reactor R1 filled with strongly basic ion exchange resin; (2) carrying out dehydration reaction on the obtained cyanation reaction feed liquid in a tubular reactor R2 filled with strongly acidic ion exchange resin; and (3) carrying out post-treatment on the feed liquid after the dehydration reaction, so as to obtain the product 17 [beta]-cyano-17 [alpha]-hydroxy-9-dehydroandrostenedione. The method has the advantages that the online reaction amount is small, the safety is high, continuous and automatic production is easy to realize, and the like; the repeated utilization rate of ion exchange resin in the tubular reactor is high, so that the process cost is reduced; the use of inorganic acid and inorganic base is eliminated from the source, the three wastes of the process are reduced, and the environment-friendly requirement is met. The reaction formula is as follows:

Description

technical field [0001] The invention relates to a method for synthesizing 17β-cyano-17α-hydroxyl-9-dehydroandrostenedione, a key intermediate of hydrocortisone. Background technique [0002] 17β-cyano-17α-hydroxy-9-dehydroandrostenedione is an important intermediate in the synthesis of steroid hormone drug hydrocortisone. Hydrocortisone has important pharmacological activities, such as anti-inflammatory, anti-viral, anti-allergic, anti-shock, etc. It is widely used clinically in the treatment of diseases such as adrenal insufficiency, rheumatoid arthritis, gout, and dermatitis. [0003] At present, the synthesis of 17β-cyano-17α-hydroxy-9-dehydroandrostenedione is mainly through the dehydration reaction under acid catalysis and the cyanation reaction under base catalysis, using 9-hydroxyandrostenedione as raw material. Realize (CN201410747239.5, CN201610204515.2, CN201811395764.X, CN201410707307.5 etc.); adopt the above-mentioned preparation 17β-cyano-17α-hydroxyl-9-dehydro...

Claims

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Application Information

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IPC IPC(8): C07J41/00
CPCC07J41/0094
Inventor 于旭超隋志红尹琳琳
Owner 台州仙琚药业有限公司
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