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Preparation method of budesonide

An intermediate and organic solvent technology, which is applied in the field of preparation of budesonide, can solve the problems of difficult product purification, low total yield, unsuitability for industrial production, etc., and achieve good market prospects, short process route, and easy operation Effect

Active Publication Date: 2020-08-21
ZHEJIANG SHENZHOU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This synthetic method will also produce 11α-hydroxyl by-products in the reduction process, which makes product purification difficult, the total yield is not high, and it is not suitable for industrial production

Method used

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  • Preparation method of budesonide

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1 A kind of preparation method of budesonide, comprises the steps:

[0033] 1) Protection reaction: Dissolve 50g of prednisolone acetate in 250ml of chloroform, add 25ml of piperidine and 20ml of trifluoroacetic anhydride, and stir the reaction at -10°C. After the reaction, wash with water, concentrate, and dry to obtain 58.2g of intermediate body 2;

[0034] 2) Dehydration reaction: Dissolve 58.2g of intermediate (2) in 582ml of pyridine, add 30g of N-chlorosuccinimide, 60ml of 30% pyridine solution of sulfur dioxide, stir and react at -20°C, after the reaction, water analysis, Filter and dry to obtain 43.7g intermediate 3;

[0035] 3) Double hydroxylation reaction: Dissolve 43.7g of intermediate (3) in 1320ml of butanone, add 4.5ml of glacial acetic acid, add 100ml of 20% potassium permanganate aqueous solution, and control the temperature at -20°C to stir the reaction. After the reaction is completed, add 5 % sodium sulfite aqueous solution 200ml, filter...

Embodiment 2

[0038] Embodiment 2 A kind of preparation method of budesonide, comprises the steps:

[0039] 1) Protection reaction: Dissolve 50g of prednisolone acetate in 1000ml of dichloromethane, add 100ml of triethylamine, 50ml of trifluoroacetic anhydride, and stir the reaction at -20°C. After the reaction, wash with water, concentrate, and dry to obtain 58.5g Intermediate 2;

[0040] 2) Dehydration reaction: Dissolve 58.5g of intermediate (2) in 120ml of 2H-pyrrole, add 70g of N-chlorosuccinimide, 250ml of 10% pyridine solution of sulfur dioxide, and stir at -40°C for reaction. After the reaction, water analysis , filtered and dried to obtain 44.1g of intermediate 3;

[0041] 3) Double hydroxylation reaction: Dissolve 44.1g of intermediate (3) in 1500ml of acetone, add 20ml of formic acid, add 440ml of 5% potassium permanganate aqueous solution, control the temperature at -10°C and stir the reaction. After the reaction is completed, add 20% sulfurous acid 20ml of sodium hydrogen aqu...

Embodiment 3

[0044] Embodiment 3 A kind of preparation method of budesonide, comprises the steps:

[0045] 1) Protection reaction: Dissolve 50g of prednisolone acetate in 500ml of toluene, add 50ml of pyridine and 60ml of trifluoroacetic anhydride, and stir at -30°C for reaction. After the reaction, wash with water, concentrate, and dry to obtain 58.0g of intermediate 2;

[0046] 2) Dehydration reaction: Dissolve 58.0g of intermediate (2) in 250ml of pyridine, add 50g of N-chlorosuccinimide, 150ml of 20% sulfur dioxide in pyridine, and stir at -30°C for reaction. After the reaction, water analysis, Filter and dry to obtain 43.8g intermediate 3;

[0047] 3) Dihydroxy reaction: dissolve 43.8g of intermediate (3) in 1700ml of acetone, add 15ml of oxalic acid, add 150ml of 15% potassium permanganate aqueous solution, control the temperature at 0°C and stir the reaction, after the reaction is completed, add 10% potassium sulfite 100ml of aqueous solution was filtered, the filtrate was concentr...

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Abstract

The invention discloses a preparation method of budesonide, and belongs to the technical field of preparation and processing of medicines. According to the method, prednisolone acetate is used as an initial raw material, and is subjected to five steps of protection, dehydration, dihydroxy, hydrolysis and condensation to prepare the budesonide. According to the preparation method, the reaction process can be effectively shortened by improving the defects of a traditional process, reaction conditions are mild, osmium tetroxide which is high in toxicity and not environmentally friendly is avoided, environmental pollution is reduced, and the method is high in overall conversion rate, easy and convenient to operate, suitable for industrial production and wide in market prospect.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a preparation method of budesonide. Background technique [0002] The chemical name of budesonide is 16α, 17α-22(R,S)propylmethylenedioxy-11β, 21-dihydroxy-1,4-pregnadiene-3,20-dione, which is a Halogen-free neide steroid adrenal cortex hormone drugs are widely used in the treatment of intractable asthma and inflammation. Budesonide has the advantages of small dosage, strong local anti-inflammatory effect, and small systemic side effects. What is more prominent is It can be applied to children, so it has become the first choice for clinical treatment of severe asthma and allergic rhinitis. [0003] Regarding the preparation process of budesonide, there have been many public reports at home and abroad: WO 87 / 05028 discloses a kind of prednisone acetate as the starting material, which undergoes esterification, reduction, elimination, oxidation, condensation and hydrol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J71/00C07J75/00
CPCC07J71/0031C07J75/00
Inventor 邵振平王荣王炳乾王洪福黄橙橙雷灵芝王友富
Owner ZHEJIANG SHENZHOU PHARMA
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