A kind of preparation 16a, the method for 21-diacetyloxy prednisolone

A kind of technology of bisacetoxyprednisolone and deoxyprednisolone is applied in the field of preparation 16a, and achieves the effects of avoiding many side reactions, economical and environmentally friendly production process, and improving the total yield of synthesis

Active Publication Date: 2020-08-11
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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  • A kind of preparation 16a, the method for 21-diacetyloxy prednisolone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Step A---preparation of epoxy:

[0039] 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

[0048] Step A: Preparation of epoxy:

[0049] 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

[0058] Step A---preparation of epoxy:

[0059] 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 16a,21-diacetyloxy prednisolone. The method comprises the following steps: adopting 17a-deshydroxy prednisolone as a raw material, firstly, enabling the starting raw material 17a-deshydroxy prednisolone to generate epoxidation reaction with organic peroxy acid on 16 and 17 sites in a first organic solvent to prepare an epoxy product; enabling the epoxyproduct to react with glacial acetic acid under the catalysis of an acid catalyst in a second organic solvent to be subjected to ring opening, to prepare a target product, i.e., 16a,21-diacetyloxy prednisolone. According to the efficient, environment-friendly and fair-price method, the intermediate 16a,21-diacetyloxy prednisolone of 16 alpha-hydroxyprednisolone is prepared.

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, 21-bisacetoxyprednisolone. 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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Patent Type & Authority Patents(China)
IPC IPC(8): C07J5/00
CPCC07J5/0092
Inventor 甘红星左前进谢来宾
Owner HUNAN KEREY BIOTECH
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