Preparation method of betamethasone intermediate

A technology of betamethasone and intermediates, which is applied in the field of preparation of steroid compounds, can solve the problems of long steps and low yield, and achieve the effects of reducing side reactions, improving yield and quality, and strong operability

Active Publication Date: 2012-07-25
HUNAN NORCHEM PHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the starting materials are cheaper and the way of dehydrogenation of the 1 and 4 positions has been changed, the steps for the synthesis of compound I are much longer, and a lot of highly toxic salts are used, which creates a lot of pressure on environmental protection, and it is also inevitable A high-temperature format reaction is used, and the yield of the whole synthesis is low

Method used

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  • Preparation method of betamethasone intermediate
  • Preparation method of betamethasone intermediate
  • Preparation method of betamethasone intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] sulfonation elimination reaction

[0043] Put in 50ml acetone and 200ml pyridine, stir, nitrogen protection, then put in 50g compound II (16a,17-epoxy-11a-hydroxyl-1,4-pregnadiene-3,20-dione), cool to -10 Below ℃, add 80ml of methanesulfonyl chloride dropwise, and keep the temperature of the reaction solution not exceeding -10℃ during the whole dropping process. After the dropwise addition, react at a constant temperature of -10°C for 5 hours. After the reaction is complete, slowly add the reaction solution dropwise to a mixed solution consisting of 1000ml of water and 200ml of concentrated hydrochloric acid. After the dropwise addition, stir at a constant temperature of 0°C for 4 hours. hour, filter off-white solid, put it into 300ml of acetic acid, then put into 60g of potassium acetate and 3g of magnesium chloride and heat up to 80°C to react for 2h, after the reaction is complete, slowly drop the reaction solution into 1200ml of water, stir for 1h, filter, and dry ...

Embodiment 2

[0051] sulfonation elimination reaction

[0052] Add 80ml n-butyl ether and 25g imidazole, stir, nitrogen protection, then drop 50g compound II, the structural formula is

[0053]

[0054] Among them, R is β-OH; R 1 for CH 2 COOCH 2 CH 3 ;

[0055] Cool down to below 20°C, add 30g p-toluenesulfonyl chloride, keep the temperature of the reaction solution not exceeding 20°C during the whole adding process. After the addition, react at a constant temperature of 10°C for 7 hours. After the reaction is complete, slowly add the reaction solution dropwise to a mixed solution composed of 1000ml of water and 200ml of concentrated hydrochloric acid. After the addition, stir at a constant temperature of 0°C for 4 hours. Filter the off-white solid, put it into 300ml of formic acid, then put 50g of sodium carbonate and 3.3g of calcium chloride into it and raise the temperature to 60°C for 4 hours. dry to obtain compound III 45g, molar yield 94.3%, by-product △ 1,4,11(12) Accounti...

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PUM

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Abstract

The invention relates to a preparation process of a betamethasone intermediate. The structural formula of the betamethasone intermediate is shown as a formula I, and is prepared by undergoing a ketone group protection reaction, a Grignard reaction and a hydrolysis deprotection reaction on a compound III; and the ketone group protection reaction comprises making a compound II, diazanyl carboxylic ether and an acid react to obtain a compound IV. The method has high yield, and contributes to protecting the environment; and the use of toxic substances is avoided. The structural formula of the compound III is shown as a formula III.

Description

technical field [0001] The invention relates to a preparation method of a steroid compound, in particular to a preparation process of a betamethasone intermediate. Background technique [0002] Betamethasone (Betamethasone) (also known as β-methasone, β-methasone, beflumethasone, betamethasone, betamethasone) chemical name: 16β-methyl-11β,17a,21-trihydroxy- 9a-fluoro-1,4,-pregnadiene-3,20-dione, molecular formula: C 22 h 29 FO 5 , molecular weight: 392.47. It and its esters such as 21-acetate, 17,21-dipropionate, 17-valerate and 21-phosphate are powerful anti-inflammatory drugs, and they are also a class of adrenocortical hormone and adrenocorticotropic hormone Hormone drugs, the main effect is anti-inflammatory and anti-allergic, so it is widely used in the treatment of rheumatoid arthritis and various skin diseases, such as active rheumatism, rheumatoid arthritis, lupus erythematosus, severe bronchial asthma, severe Dermatitis etc. Its structural formula is as follow...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J7/00C07J5/00
Inventor 刘喜荣蒋青锋杨坤
Owner HUNAN NORCHEM PHARMACEUTICAL CO LTD
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