Novel preparation of budesonide

An organic solvent and recrystallization technology, applied in steroids, respiratory diseases, organic chemistry, etc., can solve the problems of difficult strain source and screening, cumbersome steps, and high cost of industrial production, so as to facilitate the promotion of industrial production, High bioavailability and the effect of improving product yield

Active Publication Date: 2008-10-08
LUNAN PHARMA GROUP CORPORATION
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In U.S. Patent No. 3,536,586, a method for synthesizing budesonide using hydrocortisone as a starting material and a semi-biosynthetic method using bacterial strains is disclosed, but the semi-biosynthetic method often requires continuous synthesis due to the complexity of the product of oxidative dehydrogenation. Multi-stage countercurrent extraction and separation, the process is complicated, the technology and equipment requirements are high, and the source and screening of bacteria are difficult to solve domes

Method used

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  • Novel preparation of budesonide

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Experimental program
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Effect test

Embodiment 1

[0025] Embodiment 1: the preparation of intermediate I

[0026] Add 100g of prednisone acetate (0.25mol), 1000ml of DMF, 200ml of acetic anhydride, and 10g of 5-sulfosalicylic acid into the reaction flask slowly in turn, reflux for 8 hours, cool to below 5°C, pour into 15 liters of ice water, and place overnight , use NaOH to adjust the pH value to 6.0-7.0, then add 50g potassium acetate, add it to the reaction flask, react at 100-105°C for 6-7 hours under nitrogen protection, cool, pour into 8L ice water, place overnight, and suction filter , washed with water, and dried to obtain 92 g of crude product, which was recrystallized with chloroform to obtain 76 g of off-white crystals, yield 79.6%, mp 207-209°C.

Embodiment 2

[0027] Embodiment 2: the preparation of intermediate II

[0028] Add 50g of intermediate I (0.131mol), 3000ml of acetone into the reaction flask, dissolve, cool the mixture to below 0°C, add 80% H 2 o 2 100ml, controlled the reaction temperature at -10°C and stirred for 10 hours, then concentrated under reduced pressure to obtain 44g of oil, with a yield of 80.8%.

Embodiment 3

[0029] Embodiment 3: the preparation of intermediate III

[0030] Add 100g of intermediate II to 500ml of chloroform solution, add 200ml of tetrahydrofuran, slowly add 12g of sodium borohydride under stirring, stir, and control the reaction temperature at -5°C for 4 hours. After the reaction is complete, pour it into saturated saline, Stand overnight, filter, wash with water, and dry to obtain 83g of crude product. Recrystallize with 400ml of methanol-n-hexane (1:2) solution to obtain 72g of off-white crystals, yield 71.7%, mp195-201°C.

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Abstract

The invention in particular relates to a new method to prepare budesonide, belonging to medicinal synthesis. The method simplifies production process through repeated tests and experiments, greatly improves yield, reduces prodiction cost and works out the optimum temperature, time and solvent for the reaction; the conditions during the reaction are easy to realize; therefore the method is applicable to large-scale industrial production to produce budesonide.

Description

technical field [0001] The invention belongs to the field of medicine synthesis, and in particular relates to a new preparation method of the anti-asthma drug budesonide. Background technique [0002] Budesonide was developed by AstraZeneca Pharmaceutical Co., Ltd. and launched in 1981. It is an acetal-type glucocorticoid with strong anti-inflammatory effect. It is significantly stronger than beclomethasone dipropionate and other glucocorticoids, has a long acting time and has no systemic adrenal cortex hormone effect, and is more suitable for local administration. It is the first-line drug for aerosol inhalation to treat asthma and nasal spray to treat allergic reactions. Budesonide has two configurations, R and S, of which the R configuration is more effective than the S configuration. The structural formula of budesonide is (V), [0003] [0004] There have been many reports on the synthetic route and process of (V) at home and abroad, and there are mainly two synthe...

Claims

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Application Information

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IPC IPC(8): C07J71/00A61P11/06
Inventor 赵志全
Owner LUNAN PHARMA GROUP CORPORATION
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