Preparation method of (R)-budesonide

A single technology of dexbudesonide, which is applied in the field of preparation of dexbudesonide, can solve the problems of high toxicity and high price of intermediate reagents, and achieve the effect of high yield and good separation effect

Active Publication Date: 2014-03-26
CHENGDU YILUKANG MEDICAL TECH & SERVICE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to overcome the shortcomings of expensive intermediate reagents and high toxicity in the prior art, and provide a synthetic method for dexbudesonide that has mild reaction conditions, good yield, and is suitable for large-scale industrial production

Method used

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  • Preparation method of (R)-budesonide
  • Preparation method of (R)-budesonide
  • Preparation method of (R)-budesonide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Put 11β,21-dihydroxy-16α,17-[(1-methylethylene)-dioxy]pregna-1,4-diene-3,20-dione (desonide ) 5kg, purified water 80kg, ethanol 80kg, reflux to dissolve completely. The temperature was lowered to 25°C, and 0.8 kg of acetone was added dropwise, and the reaction was kept for 5 hours after the drop was completed. Concentrate in vacuo at 50°C and centrifuge. The solid was dissolved with 100 kg of ethanol, 2.2 kg of (+)-tartaric acid was added, and the temperature was raised to 65° C. for 2 hours. After the reaction was completed, the temperature was lowered to 5° C., and centrifuged to obtain dexbudesonide tartrate.

[0027] R isomer: 99.2%; S isomer: 0.8%

[0028] [a]D 20° =+116.4°(C=1,CH 2 Cl 2 )

[0029] 1 H-NMR (DCCl 3 , 400MHz): 7.28(t,1H), 6.26(d,1H), 6.02(S,1H), 5.15~5.19(m,1H), 4.48~4.91(m,3H), 4.23(t,1H), 3.01(S, 1H), 2.56(t, 1H), 2.34(d, 1H), 2.07~2.18(m, 3H), 1.47~1.51(m, 1H), 1.46(S, 3H), 1.32~1.43( m, 2H), 1.10 ~ 1.18 (m, 2H), 0.89 ~ 0.99 (m, 6H)

...

Embodiment 2

[0032] Put 3kg of dexbudesonide tartrate in the above example into the reactor, add 10kg of purified water and 10kg of ethanol. Cool down to 0°C, add dropwise 0.5% sodium bicarbonate solution to adjust the pH to 7.5. Concentrate in vacuo to stop flow, centrifuge, and wash with purified water to obtain 1.8 kg of dexbudesonide.

[0033] R isomer: 99.2%; S isomer: 0.8%

Embodiment 3

[0035] Put 11β,21-dihydroxy-16α,17-[(1-methylethylene)-dioxy]pregna-1,4-diene-3,20-dione (desonide ) 5kg, purified water 80kg, ethanol 80kg, reflux to dissolve completely. The temperature was lowered to 25°C, and 0.8 kg of acetone was added dropwise, and the reaction was kept for 5 hours after the drop was completed. Concentrate in vacuo and centrifuge. The solid matter was put into a reaction kettle, 100 kg of ethanol and 4 kg of (+)-camphorsulfonic acid were added, and the temperature was raised to 65° C. for 2 hours. After the reaction was completed, the temperature was lowered to 5° C., and centrifuged to obtain dexbudesonide tartrate.

[0036] R isomer: 99.7%; S isomer: 0.3%

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Abstract

The invention relates to a preparation method of adrenocortical hormone agents, and particularly discloses a preparation method of (R)-budesonide. 11beta,21-dihydroxy-16alpha,17- [(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione is taken as an initial raw material, and the budesonide (R-isomer) is obtained through exchange and splitting. The preparation method of the (R)-budesonide is simple in process, high in yield and suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of adrenocortical hormone drugs, in particular to a preparation method of dexbudesonide. Background technique [0002] Budesonide is a glucocorticoid with highly effective local anti-inflammatory effect developed by AB Bofors in Sweden. Budesonide is a racemate composed of two isomers 22R and 22S at the C-22 position in a ratio of approximately 1:1. It is clinically used topically to treat skin or respiratory symptoms caused by inflammation and allergies (such as skin diseases, asthma and rhinitis), etc. [0003] Dexbudesonide (R isomer) belongs to adrenal corticosteroid drugs, and is a single isomer at the C-22 position of budesonide prepared by chemical synthesis. Its local anti-inflammatory activity (rat auricle swelling method) is 1.4 to 1.7 times that of budesonide, 1.6 to 2 times that of levobudesonide (S isomer), and 13 times that of dexamethasone; the local glucocorticoid effect (human vasoconstri...

Claims

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Application Information

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IPC IPC(8): C07J71/00
Inventor 骆均勇陶长戈
Owner CHENGDU YILUKANG MEDICAL TECH & SERVICE
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