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Method for preparing 16a-hydroxyprednisolone product

A technology of hydroxyprednisolone and dehydroxyprednisolone, applied in the field of preparation of steroid hormone drug intermediates, to achieve the effects of avoiding many side reactions, economical and environmentally friendly production process, and improving the total yield of synthesis

Active Publication Date: 2019-01-18
HUNAN KEREY BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Therefore, generally speaking, there is not a kind of "avoiding the use of strong oxidizing agents such as potassium permanganate" in the prior art but can be efficient, environmentally friendly and inexpensive to prepare 16α-hydroxyprednisolone technology

Method used

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  • Method for preparing 16a-hydroxyprednisolone product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Step A---preparation of epoxy:

[0038] In a 3000ml three-neck flask, add 100g of starting material 17a-dehydroxyprednisolone, 1000ml of ethyl acetate, stir at room temperature to completely dissolve the solid, and add 40g of o-peroxy The peracid solution made of phthalic acid and 500ml ethyl acetate should be dripped in about 2-2.5 hours, and then keep warm at 25-30°C for 6-12 hours. TLC confirms the end point of the reaction. , add a mixed solution of 400ml 5% sodium hydroxide and 100ml 10% sodium sulfite to neutralize and destroy the acid produced by the reaction and excess peroxyacid, then concentrate under reduced pressure below 50°C to recover 90-95% ethyl acetate , then lowered to room temperature, added 500ml of tap water, stirred and analyzed for 3-4 hours, filtered, the filtrate was discharged into the wastewater treatment tank, the filter cake was washed with water, and dried below 60°C to obtain 99.3g of 16,17a-epoxyprednisolone , HPLC content 97.8%, weight...

Embodiment 2

[0047] Step A: Preparation of epoxy:

[0048] In a 3000ml three-necked flask, add 100g of starting material 17a-dehydroxyprednisolone, 1000ml of chloroform, stir at room temperature to completely dissolve the solid, and add 40g of m-chloroperoxybenzene dropwise under temperature control at 25-30°C For the peracid solution made of formic acid and 500ml ethyl acetate, drop it in about 2-2.5 hours, then continue to keep warm at 25-30°C for 6-12 hours, and confirm the end point of the reaction by TLC. After the reaction, add 400ml A mixed solution of 5% sodium hydroxide and 100ml 10% sodium sulfite to neutralize and destroy the acid and excess peroxyacid produced by the reaction, then concentrate under reduced pressure below 50°C to recover 90-95% of chloroform and ethyl acetate Mix the solvent, then lower it to room temperature, add 500ml of tap water, stir and analyze for 3-4 hours, filter, discharge the filtrate into the wastewater treatment tank, wash the filter cake with wate...

Embodiment 3

[0057] Step A---preparation of epoxy:

[0058] In a 3000ml three-necked flask, add 100g of starting material 17a-dehydroxyprednisolone and 1000ml of DME, stir at room temperature to completely dissolve the solid, and add dropwise a mixture of 40g of peracetic acid and 500ml of DME at 25-30°C under temperature control. The resulting peracid solution was dropped in about 2-2.5 hours, and then continued to insulate and react at 25-30°C for 6-12 hours. TLC confirmed the reaction end point. After the reaction, add 400ml 5% sodium hydroxide and 100ml A mixed solution made of 10% sodium sulfite is used to neutralize and destroy the acid and excess peroxyacid produced by the reaction, then concentrate under reduced pressure below 50°C to recover 90-95% DME solvent, then lower it to room temperature, add 500ml of tap water, and stir Water analysis for 3-4 hours, filtration, the filtrate was discharged into the waste water treatment tank, the filter cake was washed with water, and dried...

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Abstract

The invention provides a method for preparing a 16a-hydroxyprednisolone product. The method comprises the steps that 17a-dehydroprednisolone is used as a raw material, and firstly the starting material 17a-dehydroprednisolone performs an epoxidation reaction with organic peroxide acid at 16 and 17 sites in a first organic solvent to prepare an epoxy material; then the epoxy material reacts with glacial acetic acid under catalysis of an acid catalyst in a second solvent for loop opening, and thus 16a,21-diacetoxyprednisolone is prepared; 16a,21-diacetoxyprednisolone is dissolved in a third organic solvent, under the catalytic action of a solid-phase base catalyst, acetic ester on the two sites are hydrolyzed, and thus 16a-hydroxyprednisolone is prepared; and finally the 16a-hydroxyprednisolone crude product obtained by solid-phase base-catalyzed hydrolysis is heated and refluxed, decolorized, and recrystallized through low-carbon alcohol below C4, and thus the 16a-hydroxyprednisolone product is obtained. According to the method, 16a-hydroxyprednisolone is prepared in an efficient, environment-friendly and low-cost mode.

Description

technical field [0001] The invention belongs to the preparation technology of steroid hormone drug intermediates, and specifically refers to a method for preparing 16a-hydroxyprednisolone products. Background technique [0002] 16a-hydroxyprednisolone (molecular formula C 21 h 28 o 6 ), chemically named 11b, 16a, 17a, 21-tetrahydroxy-pregna-1,4-diene-3,20-dione, is a key intermediate in the production of nedadrenoid steroid adrenocorticotropic hormone drugs , using it as a raw material, one-step condensation reaction with acetone can produce desonide, and one-step condensation reaction with n-butyraldehyde can produce budesonide. For example, budesonide is mainly used clinically for the treatment of many diseases such as various rhinitis, acute and chronic bronchitis, etc., with low side effects, good effect and broad market prospect. The traditional production method of 16a-hydroxyprednisolone is to use prednisolone as raw material, through 17,21-position diesterization...

Claims

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Application Information

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IPC IPC(8): C07J5/00
CPCC07J5/0092
Inventor 左前进羊向新龙能吟
Owner HUNAN KEREY BIOTECH
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