Method for preparing cortisone acetate in one pot

A technology of cortisone acetate and acid catalyst, applied in the direction of steroids, organic chemistry, etc., can solve the problems of complicated post-treatment, large amount of waste water, serious environmental pollution, etc., and achieve reduced production costs, reduced emissions, and obvious The effect of competitiveness

Active Publication Date: 2019-06-28
HENAN LIHUA PHARMA
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0003] Chinese patents CN201210496816.9 and CN201410150052.7 relate to the synthesis of cortisone acetate intermediates and cortisone acetate, which use 4-pregnene-11α, 17α-dihydroxy-3,20-dione as raw materials. Cortisone acetate is prepared by oxidation, iodine addition, replacement and other reactions. Although the synthesis steps of the above route are short, the starting material needs to undergo biological fermentation, and the fermentation process is more complicated. At the same time, the reaction still uses iodine, which still has high cost and waste water volume. big problem
[0007] The process introduced by this method has been greatly improved on the previous basis, but there are still many problems, including complicated post-treatment, organic solvents are not recycled, etc., each step still produces a large amount of waste water, which is more harmful to the environment. Serious; and each step needs to be centrifugally discharged, which will cause the loss of the target product, waste manpower, material resources and energy, which does not conform to the concept of energy saving, environmental protection and green development

Method used

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  • Method for preparing cortisone acetate in one pot
  • Method for preparing cortisone acetate in one pot
  • Method for preparing cortisone acetate in one pot

Examples

Experimental program
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Effect test

Embodiment 1

[0020] A. Under nitrogen protection, add 20ml of acetone, 80ml of chloroform, and 1ml of 70% perchloric acid into the reaction flask, cool down to -5-0°C, add 20g of anecortamate acetate, 10g of dibromohydantoin in sequence, and keep warm React for 5 hours, TLC (dichloromethane: acetone = 6:1) detects no spots at Rf 0.91, add 15ml of 20% sodium sulfite solution to quench the reaction;

[0021] B. Slowly add 20ml of Jones reagent to the reaction solution, keep the temperature at 0-5°C, and keep the temperature for about 1 hour. After the drop is completed, keep the reaction for 3 hours. ) Detect that there is no spot at Rf 0.75, add 30ml of 20% sodium sulfite solution to quench the reaction;

[0022] C. Add 20ml of drinking water to the system, stir for 5 minutes, let stand for 30 minutes, separate the organic layer, extract the water layer with 20ml of chloroform, combine the organic layers, add 10ml of glacial acetic acid to the organic layer, and control the temperature for ...

Embodiment 2

[0024] A. Under the protection of nitrogen, add 20ml of acetone, 80ml of chloroform, and 2ml of 40% fluoroboric acid into the reaction bottle, cool down to -5-0°C, add 20g of anecortamate acetate, 10g of dibromohydantoin in sequence, and keep warm for the reaction After 5 hours, TLC (dichloromethane: acetone = 6:1) detected no spots at Rf 0.91, and added 15ml of 20% sodium sulfite solution to quench the reaction;

[0025] B. Slowly add 20ml of Jones reagent to the reaction solution, keep the temperature at 0-5°C, and keep the temperature for about 1 hour. After the drop is completed, keep the reaction for 3 hours. ) Detect that there is no spot at Rf0.75, add 30ml of 20% sodium sulfite solution to quench the reaction;

[0026] C. Add 20ml of drinking water to the system, stir for 5 minutes, let stand for 30 minutes, separate the organic layer, extract the water layer with 20ml of chloroform, combine the organic layers, add 10ml of glacial acetic acid to the organic layer, and ...

Embodiment 3

[0028] A. Under the protection of nitrogen, add 20ml of acetone, 100ml of dichloromethane, and 1ml of 70% perchloric acid into the reaction bottle, cool down to -5-0°C, add 20g of anecortamate acetate, 10g of dibromohydantoin in sequence, and keep warm React for 5 hours, TLC (dichloromethane: acetone = 6:1) detects no spots at Rf0.91, add 15ml of 20% sodium sulfite solution to quench the reaction;

[0029] B. Slowly add 20ml of Jones reagent to the reaction solution, keep the temperature at 0-5°C, and keep the temperature for about 1 hour. After the drop is completed, keep the reaction for 3 hours. ) Detect that there is no spot at Rf0.75, add 30ml of 20% sodium sulfite solution to quench the reaction;

[0030] C. Add 20ml of drinking water to the system, stir for 5 minutes, let stand for 30 minutes, separate the organic layer, extract the water layer with 20ml of dichloromethane, combine the organic layers, add 10ml of glacial acetic acid to the organic layer, and control the...

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Abstract

Provided is a method for preparing cortisone acetate in one pot. According to the method, Anecortave acetate is adopted as a raw material, and after the raw material is added into an organic solvent,a pot is adopted for preparation. The method comprises the following steps of A, adding a compound I into a mixed organic solvent and adding a halogenating reagent and an acid catalyst, wherein the reaction temperature is controlled in a range from -10 DEG C to 30 DEG C; after the reaction is finished, adding a quencher to quench the reaction, wherein the quencher comprises a sodium sulfite solution or a sodium bisulfite solution; B, adding an oxidant into a system finally obtained in step A, wherein the oxidant is a Jones reagent or pyridine chlorochromate or a Dess-Martin oxidant used for anoxidization reaction, and the reaction temperature is controlled in a range from -10 DEG C to 30 DEG C; after the reaction is finished, adding the quencher to quench the reaction; C, adding an organic acid catalyst and a reducing agent into an organic layer finally obtained in step B to obtain a target product cortisone acetate IV. The preparation method greatly reduces the discharge amount of waste liquid.

Description

technical field [0001] The invention relates to drug synthesis, in particular to a method for preparing cortisone acetate, which belongs to the field of chemical technology. Background technique [0002] Cortisone Acetate (Cortisone Acetate), also known as corticosterone acetate (Adreson), is a steroid hormone It is an important intermediate in the class of APIs, and can be used to synthesize various high value-added APIs such as prednisone acetate and hydrocortisone. At present, it is recorded in Chinese, American and European pharmacopoeias. Cortisone acetate is a medium-acting adrenal cortex hormone drug, which acts on glucose metabolism and has a certain impact on electrolyte metabolism. For severe bronchial asthma, severe dermatitis and other allergic diseases, active rheumatism, rheumatoid arthritis, lupus erythematosus and other diseases. [0003] Chinese patents CN201210496816.9 and CN201410150052.7 relate to the synthesis of cortisone acetate intermediates and cor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J5/00
Inventor 王海波薛潇陈玉真李合兴
Owner HENAN LIHUA PHARMA
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