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Preparation method of methyl metacortandracin

A technology of methylprednisone and methylprednisone acetate, applied in the field of steroid hormone drug preparation, can solve the problems of uneconomical and environmentally friendly synthesis, complex process operation, expensive production raw materials, etc. Economic and environmental protection, easy production and operation

Inactive Publication Date: 2017-11-03
HUNAN KEREY BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of the invention is to provide a new preparation method of methylprednisone, to solve the technical problems of expensive raw materials, difficult sewage treatment, complicated process operation and high production cost in the traditional production process of methylprednisone; For the CN201610952306.6 methylprednisone preparation method, the production raw materials are scarce and hard to find, and the single synthesis is uneconomical and environmentally friendly. It also greatly improves the total synthesis yield and significantly reduces its production cost.

Method used

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  • Preparation method of methyl metacortandracin
  • Preparation method of methyl metacortandracin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] A. Synthesis of bromohydryl compounds

[0025] In a 1000ml three-neck flask, add 100g DB11, 250ml glacial acetic acid, 100g 40% hydrobromic acid, keep warm at 20-25 degrees and stir for 4-6 hours. TLC detects the reaction end point. After the reaction, add 100g 20% ​​caustic soda Neutralize the solution, then concentrate under reduced pressure to recover the solvent, cool, add 500ml of tap water, stir and crystallize for 60-90 minutes, centrifuge, wash, spin filter, discharge the filtrate and washing liquid to the waste water treatment pool, and dry the filter cake to obtain bromohydroxyl Product: 9a bromo-16b methyl-prednisolone acetate 122g, HPLC content 98.5%, weight yield 122%;

[0026] B. Synthesis of debrominated compounds

[0027] In a 2000ml three-necked flask, add 100g bromohydroxide, 1000ml DMF, completely dissolve bromohydroxide at 20-25 degrees, feed nitrogen, stir, add 60g ammonium acetate and 5g 1% palladium carbon catalyst, replace the air, Keep warm at...

Embodiment 2

[0033] A. Synthesis of bromohydryl compounds

[0034] In a 1000ml three-necked flask, add 100g DB11, 250ml chloroform, and 100g 40% hydrobromic acid, keep warm at 20-25 degrees and stir for 4-6 hours. TLC detects the reaction end point. After the reaction, add 100g 20% ​​caustic soda solution Neutralize, separate water, wash, dry with anhydrous sodium sulfate, then concentrate under reduced pressure to recover the solvent, cool, add 500ml tap water, stir and crystallize for 60-90 minutes, centrifuge, wash, spin filter, and discharge the filtrate and lotion to Waste water treatment pond, filter cake is dried to obtain bromohydroxyl product: 9a bromo-16b methyl-prednisolone acetate 120g, HPLC content 99.0%, weight yield 120%;

[0035] B. Synthesis of debrominated compounds

[0036] In a 2000ml three-necked flask, add 100g bromohydroxide, 1000ml 90% ethanol, completely dissolve the bromine hydroxy substance at 20-25 degrees, feed nitrogen, stir, add 60g sodium bicarbonate and 5g...

Embodiment 3

[0042] A. Synthesis of bromohydryl compounds

[0043] In a 1000ml three-neck flask, add 100g DB11, 250ml alcohol, 100g 40% hydrobromic acid, keep warm at 20-25 degrees and stir for 4-6 hours. TLC detects the reaction end point. After the reaction, add 100g 40% sodium carbonate Neutralize the solution, then concentrate under reduced pressure to recover the solvent, cool, add 500ml of tap water, stir and crystallize for 60-90 minutes, centrifuge, wash, spin filter, discharge the filtrate and washing liquid to the waste water treatment tank, and dry the filter cake to obtain the bromohydroxyl compound : 9a bromo-16b methyl-prednisolone acetate 121g, HPLC content 99.2%, weight yield 121%;

[0044] B. Synthesis of debrominated compounds

[0045]In a 2000ml three-necked flask, add 100g of bromohydrin and 1000ml of 90% ethanol, completely dissolve the bromohydrin at 20-25 degrees, blow in nitrogen, stir, add 60g of triethylamine and 15g of Raney nickel catalyst, and replace the air ...

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Abstract

The invention discloses a preparation method of methyl metacortandracin. The methyl metacortandracin is prepared by taking 16-b methyl-9 (11) a-epoxy-prednisolone acetate (called as DB11 for short) as a raw material; dissolving the raw material in an organic solvent and reacting with hydrobromic acid to obtain bromine hydroxyl content 9a bromine-16b methyl-prednisolone acetate; performing catalytic hydrogenation and 9-bit debromination on bromine hydroxyl content in the organic solvent by acid-binding agent and palladium carbon to obtain a debromination matter 16b methyl-metacortandracin; oxidizing the debromination matter with strong oxidant in the organic solvent to obtain prednisolone acetate; finally, hydrolyzing the prednisolone acetate in the organic solvent by catalyst to obtain methyl metacortandracin. The total weight yield through four-step synthesis is 52-55%. The production method is wide in raw material source, economic and environment-friendly in technique, short in synthesis route, and high in production yield; the production cost is 30-40% lower than that of the traditional method, and 15-20% lower than the method of application number 201610952306.6; the technique is simple and convenient; the solvent can be recycled and used indiscriminately; the preparation method is easy to practice the industrial production.

Description

technical field [0001] The invention belongs to the preparation process of steroid hormone drugs, and specifically refers to a production method for synthesizing methylprednisolone through four steps by using prednisolone acetate (abbreviated as DB11) as a raw material. Background technique [0002] Methylprednisone (molecular formula C22H30O5), chemical name 16b-methyl-17a, 21-dihydroxy-pregna-1,4-diene-3,11,20-trione, is a second-generation steroidal sugar corticosteroid drugs. Clinically, it is mainly used for the treatment of primary and secondary adrenal cortex hypofunction, cerebral edema, rheumatism, acute bronchitis, skin disease, lupus erythematosus, nausea and vomiting caused by tumor chemotherapy, etc., with low side effects. The effect is good and the market prospect is broad. The traditional production method of methylprednisone is to use the diosgenin extracted from the yam plant, through six steps of chemical reaction, plus two steps of microbial fermentatio...

Claims

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Application Information

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IPC IPC(8): C07J5/00
CPCC07J5/0053
Inventor 甘红星左前进胡爱国谢来宾
Owner HUNAN KEREY BIOTECH
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