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A kind of preparation method of 17a-prednisolone dehydroxyacetate product

A technology of prednisolone dehydroxyacetate and prednisolone acetate, which is applied in the production process field of synthesizing 17a-prednisolone dehydroxyacetate, can solve the problems of high production cost, low synthesis yield and many side reactions and other problems, to achieve the effect of simple and convenient production operation, high yield and reduced preparation cost

Active Publication Date: 2021-01-01
HUNAN KEREY BIOTECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The object of the invention is to propose a kind of new 17a-prednisolone dehydroxyacetate synthetic method at above-mentioned traditional 17a-prednisolone dehydroxyacetate synthetic side reaction is many, synthetic yield is low production cost height etc. To overcome the many defects of the existing 17a-dehydroxyacetate prednisolone traditional production process

Method used

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  • A kind of preparation method of 17a-prednisolone dehydroxyacetate product
  • A kind of preparation method of 17a-prednisolone dehydroxyacetate product

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preparation example Construction

[0018] Further, the specific operation steps of the preparation method of 17a-prednisolone dehydroxyacetate are as follows:

[0019] Step A, preparation of protective material: dissolve prednisolone acetate in an organic solvent, add alkali catalyst and trimethylchlorosilane, stir and react at 10-50°C for 3-4 hours, after the reaction, evaporate under reduced pressure Organic solvent, then adding tap water for water analysis, filtering, washing, and drying to obtain the protected product: 11-trimethylsilyl etherified prednisolone acetate, with a weight yield of about 120-125%;

[0020] Step B. Preparation of 17a-prednisolone dehydroxyacetate: Dissolve the protective compound prepared in the above A into an organic solvent, add an organic base catalyst, and keep warm at 10-100°C and feed SO 3 Gas dehydration reaction for 6-12 hours, TLC to confirm the reaction end point, after the reaction, directly add acid aqueous solution to hydrolyze and deprotect at 10-100 ° C, TLC to conf...

Embodiment 1

[0029] Step A, preparation of protection:

[0030] In a 1000ml three-necked bottle, add 100g prednisolone acetate, 600ml dichloromethane, 100g pyridine, stir to dissolve the solid completely, slowly add 80g trimethylchlorosilane dropwise at 20-25℃, about 1.5-2 After adding in 1 hour, continue to insulate and stir the reaction at 20-25°C for 3 to 4 hours after dropping, and confirm the end point of the reaction by TLC. After the reaction, 90-95% of the organic solvent dichloromethane is recovered by vacuum distillation below 30°C, and then Add 600ml of tap water, stir and crystallize at 10-15°C for 3-4 hours, filter, send the filtrate to a wastewater treatment tank for treatment, wash the filter cake with water, and dry it below 60°C to obtain the protected product: 11-trimethylsilyl etherified acetic acid Prednisolone 123.6g, HPLC content 97.6%, weight yield 123.6%;

[0031] B, preparation 17a-prednisolone dehydroxyacetate:

[0032] In a 2000ml three-necked flask, add 100g o...

Embodiment 2

[0036] A. Preparation of protective materials:

[0037] In a 1000ml three-necked bottle, add 100g of prednisolone acetate, 600ml of chloroform, and 80g of triethylamine, stir to dissolve the solid completely, and slowly add 80g of trimethylchlorosilane dropwise at 20-25°C, about 1.5 - After adding in 2 hours, continue to insulate and stir the reaction at 20-25°C for 3-4 hours, and confirm the end point of the reaction by TLC. After the reaction, recover 90-95% of the organic solvent chloroform by distillation under reduced pressure below 30°C , then add 600ml of tap water, stir and crystallize at 10-15°C for 3-4 hours, filter, send the filtrate to the wastewater treatment tank for treatment, wash the filter cake with water, and dry below 60°C to obtain the protected product: 11-trimethylsilyl ether Prednisolone acetate 123.2g, HPLC content 97.2%, weight yield 123.2%;

[0038] B, preparation 17a-prednisolone dehydroxyacetate:

[0039] In a 2000ml three-neck flask, add 100g of...

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Abstract

The invention provides a preparation method of a 17a-dehydroxy prednisolone acetate product. The method includes the following steps: step A, dissolving prednisolone acetate in a first organic solvent, and subjecting the solvent and trimethylchlorosilane to 11th-position silicon etherification reaction under the catalysis of organic base to obtain a protector; step B, in a second organic solvent,subjecting the protector and SO3 to 17th-position dehydration reaction under the catalysis of the organic base, directly adding acid for treatment after the reaction to deprotect the 11th position, and obtaining a crude 17a-dehydroxy prednisolone acetate product; subjecting the crude product to decolorization and recrystallization in the presence of C4-below low carbon alcohol and activated carbonto obtain the 17a-dehydroxy prednisolone acetate product. The preparation method has the advantages that the problems such as many side reactions and impurities and difficulty in impurity refining inthe dehydration reaction in a traditional production process of 17a-dehydroxy prednisolone acetate are solved, the total synthesis yield is remarkably increased, and the production cost is reduced.

Description

technical field [0001] The invention belongs to the preparation technology of steroid hormone drug intermediates, and specifically refers to a production technology for synthesizing 17a-dehydroprednisolone acetate by using prednisolone acetate as a raw material. Background technique [0002] 17a-prednisolone dehydroxyacetate (molecular formula C 23 h 26 o 6 ), chemically named 11b,21-dihydroxypregna-1,4,16-triene-3,20-dione-21-acetate, is a steroid that produces deflazacort and nedd The key intermediate of corticosteroid drugs, using it as a raw material, can synthesize deflazacort through 3-step reactions, and can also prepare desonide and budesonide through 3-step reactions. Deflazacort, a third-generation steroidal glucocorticoid drug, is mainly used clinically for primary and secondary adrenal cortical insufficiency, rheumatism, collagen disease, skin disease, fulminant and The treatment of disseminated pulmonary tuberculosis, hematopoietic system diseases, ulcerativ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J5/00
Inventor 谢来宾胡爱国羊向新
Owner HUNAN KEREY BIOTECH
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