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Preparation method of hydrocortisone acetate

A technology for hydrocortisone acetate and a compound, which is applied in the field of chemical synthesis of steroid hormone drugs, can solve the problems of low oxidative conversion rate, limited yield, low deacetylation activity of Curvilla crescentus, and the like, and achieves low cost , Reduce the dependence of high-end equipment, the effect of easy availability

Active Publication Date: 2016-08-03
湖南成大生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Generally speaking, Curvularia lunata has low deacetylation activity to 17α, 21-dihydroxy-4-pregnene-3,20-dione-21-acetate, and the substrate is Transformation, although hydrocortisone can be obtained from the β-OH at the C11 position, but at the same time a 14α-OH by-product is also produced, usually the acetyl group at the C21 position is hydrolyzed first, and then directly introduced into the C11 position by Curvularia lunata oxidation β-OH, but the oxidative conversion rate of Curvularia crescens is not high, and the yield of hydrocortisone is limited

Method used

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  • Preparation method of hydrocortisone acetate
  • Preparation method of hydrocortisone acetate
  • Preparation method of hydrocortisone acetate

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Experimental program
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Effect test

Embodiment 1

[0057] Present embodiment is a kind of preparation method of hydrocortisone acetate, comprises the following steps:

[0058] Alkynylation reaction: at room temperature, add 1000ml of anhydrous tetrahydrofuran to a clean and dry 2000ml four-neck round-bottomed flask equipped with a thermometer and mechanical stirring, add 300.0g of compound A to the four-necked round-bottomed flask, and pass it through for drying treatment acetylene gas, add 160g of potassium tert-butoxide, stir evenly, control the temperature of the system at 30-40°C and react for 8 hours, and the liquid phase detection raw materials will no longer decrease. The reaction system was added dropwise to 2000ml of water for water analysis, and stirred for 2 hours. Suction filtration, washing the filter cake with water to neutrality, and drying at 50°C to obtain 320 g of compound B with an HPLC purity of 98.9%.

[0059] Solid-supported catalytic oxidation reaction: at room temperature, add 600ml methylene chloride ...

Embodiment 2

[0062] Present embodiment is a kind of preparation method of hydrocortisone acetate, comprises the following steps:

[0063] Alkynylation reaction: at room temperature, add 1500ml tetrahydrofuran to a 2000ml four-necked round-bottomed flask equipped with a clean and dry thermometer and mechanically stirred, add 400.0g of compound A to the four-necked round-bottomed flask, and pass through the dried acetylene Gas, add 180g of sodium tert-butoxide, stir evenly, control the temperature of the system at 30-40°C and react for 10 hours, and the liquid phase detection raw materials will no longer decrease. The reaction system was added dropwise to 2000ml of water for water analysis, and stirred for 2 hours. After suction filtration, the filter cake was washed with water until neutral, and then dried at 50° C. to obtain 22 g of compound B with an HPLC purity of 98.0%.

[0064] Solid-supported catalytic oxidation reaction: at room temperature, add 600ml methylene chloride and 6.5g sul...

Embodiment 3

[0067] Present embodiment is a kind of preparation method of hydrocortisone acetate, comprises the following steps:

[0068] Alkynylation reaction: at room temperature, add a total of 1200ml of ether and dioxane to a clean and dry 2000ml four-necked round-bottomed flask equipped with a thermometer and mechanical stirring, and add 300.0g of compound A to the four-necked round-bottomed flask. Introduce dried acetylene gas, add sodium potassium hydroxide and potassium acetate in total 180g, stir evenly, control the temperature of the system at 20-35°C and react for 12 hours, and the raw materials for liquid phase detection will no longer decrease. The reaction system was added dropwise to 2000ml of water for water analysis, and stirred for 2 hours. After suction filtration, the filter cake was washed with water until neutral, and then dried at 50° C. to obtain 306 g of compound B with an HPLC purity of 99.8%.

[0069] Solid-supported catalytic oxidation reaction: at room tempera...

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Abstract

The invention relates to a preparation method of hydrocortisone acetate. A steroid raw material compound A is subjected to alkynylation reaction, solid-supported catalytic oxidation reaction and addition reaction to prepare hydrocortisone acetate. According to the method, the starting material is a basic steroid raw material, the source is easy to obtain, the cost is low, the synthesis procedure is short, all steps of reaction are relatively easy to implement, the yield is high, the catalyst and the carrier can be recycled, dangerous and toxic materials such as bromine are avoided, the dependence on high-end equipment is greatly reduced, the environment pollution is reduced, the production is more economic and environmental-friendly and safer, and the preparation method of the hydrocortisone acetate is more suitable for industrial production.

Description

technical field [0001] The invention relates to a chemical synthesis method of steroid hormone drugs, in particular to a preparation method of hydrocortisone acetate. Background technique [0002] Hydrocortisone acetate is mainly used to treat rheumatoid arthritis, rheumatic fever, gout, and bronchial asthma. Injections can be used for tuberculous or suppurative meningitis, tuberculous pleurisy, empyema, arthritis, tenosynovitis, tendon strain, sprains, prurigo nodosa, lichen planus, etc. Eye drops are used for various ophthalmic conditions. Creams are used for allergic or seborrheic dermatitis, pruritus, etc. Due to environmental pollution, fast pace of work, lack of exercise and other reasons, the number of people with rheumatic or rheumatoid arthritis is increasing, and it is showing a younger trend. In my country, the incidence rate of rheumatoid arthritis is 0.2%-0.4%. Therefore, the number of rheumatoid arthritis in my country has reached as many as 5 million. Mor...

Claims

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Application Information

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IPC IPC(8): C07J5/00
CPCC07J5/00
Inventor 何卫民吴超刘喜荣
Owner 湖南成大生物科技有限公司
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