Preparation method of cefodizime acid

A technology of cefodizime acid and aminocephalosporanic acid, which is applied in the field of preparation of cefodizime acid, can solve the problems of recrystallization purification, low product yield, and low purity of cefodizime acid, so as to improve yield and ensure The effect of product quality

Active Publication Date: 2013-01-02
SHANDONG JINCHENG PHARMACEUTICAL GROUP CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The yield of the product produced by this process is low, and the purity of the prepared cefodizime acid is low, which requires recrystallization and purification

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 90kg of water and 25.5kg of 2-mercapto-4-methyl-5-thiazoleacetic acid to the reactor, start stirring, add 7.5kg of sodium carbonate; heat up to 30°C, add 30kg of 7-aminocephalosporanic acid, and start adding 225kg of Dissolve 12.6g of sodium carbonate in deionized water to form a solution, control the dropping time for 1 hour, continue to keep warm for 1 hour after dropping, add 90kg of ethyl acetate to the filtrate, adjust pH=2-4 with glacial acetic acid, and get 7-amino- 3-(5-carboxymethyl-4-methyl-1,3-thiazole-2-mercaptomethyl)ceph-2-ene-2-carboxylic acid, rinse with methanol, and use 7-amino -3-(5-carboxymethyl-4-methyl-1,3-thiazole-2-mercaptomethyl)ceph-2-ene-2-carboxylic acid wet product was put into dichloromethane solvent, and 39kg2- Methoxyimino-2-(2-amino-4-thiazolyl)-(z)-phenylhydrazine thioacetate, add 60kg of N,N-dimethylformamide dropwise within 2h, react for 5h, extract with water Use glacial acetic acid to adjust the pH to 2-4, cool down to 0°C afte...

Embodiment 2

[0024] Add 90kg of water and 25.5kg of 2-mercapto-4-methyl-5-thiazoleacetic acid to the reactor, start stirring, add 10kg of sodium hydroxide; heat up to 70°C, add 30kg of 7-aminocephalosporanic acid, and start adding 225kg of Dissolve 12.6g of sodium hydroxide in deionized water to make a solution, control the dropping time for 2 hours, continue to keep warm for 1 hour after the dropping, add 90kg of methanol to the filtrate, adjust the pH=2-4 with glacial acetic acid, and get 7-amino-3 -(5-carboxymethyl-4-methyl-1,3-thiazole-2-mercaptomethyl)ceph-2-ene-2-carboxylic acid, wash with ethanol, and use 7-amino- 3-(5-carboxymethyl-4-methyl-1,3-thiazole-2-mercaptomethyl)ceph-2-ene-2-carboxylic acid wet product was put into dichloromethane solvent, and 39kg2-formazol Oxyimino-2-(2-amino-4-thiazolyl)-(z)-phenylhydrazine thiazolyl thioacetate, add 60 kg of N,N-dimethylacetamide dropwise within 2 hours, react for 5 hours, extract with water and use Adjust the pH to 2-4 with glacial ac...

Embodiment 3

[0026] Add 90kg of water and 25.5kg of 2-mercapto-4-methyl-5-thiazoleacetic acid to the reactor, start stirring, add 7.9kg of sodium methoxide; heat up to 15°C, add 30kg of 7-aminocephalosporanic acid, and start adding 225kg of Dissolve 12.6g of sodium bicarbonate in deionized water to form a solution, control the dropping time for 2 hours, continue to keep warm for 1 hour after the dropping, add 90kg of ethyl acetate to the filtrate, adjust the pH to 2-4 with glacial acetic acid, and get 7-amino -3-(5-carboxymethyl-4-methyl-1,3-thiazole-2-mercaptomethyl)ceph-2-ene-2-carboxylic acid, wash with acetone, and use 7- Amino-3-(5-carboxymethyl-4-methyl-1,3-thiazole-2-mercaptomethyl)ceph-2-ene-2-carboxylic acid wet product was put into dichloromethane solvent, adding 39kg2 -Methoxyimino-2-(2-amino-4-thiazolyl)-(z)-phenylhydrazine thioacetate, add 60kg of N,N-dimethylformamide dropwise within 2h, react for 5h, extract with water Finally, use glacial acetic acid to adjust the pH to 2-...

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Abstract

The invention belongs to the technical field of medicament synthesis, and particularly relates to a preparation method of cefodizime acid. The preparation method is characterized by comprising the following steps of: adding 7-aminocephalosporanic acid, 2-Mercapto-4-methyl-1,3-thiazol-5-yl-acetic acid(MMTA) and water, dropwise adding an alkaline solution, adjusting pH, adding an organic solvent, stirring and mixing, and adjusting pH by using glacial acetic acid; leaching, rinsing by the organic solution, and drying; directly adding the dried substance obtained from the former step into a dichloromethane solution after rinsing, adding 2-methoxy imino-2-(2-azyl-4-thiazolyl)-(z)-thioacetic acid phenylhydrazine thiazole ester, and dropwise adding a 7-aminocephalosporanic acid basic catalyst for reaction; and extracting with water, and adjusting pH with glacial acetic acid to obtain cefodizime acid. After the special alkaline solution is used, the reaction yield of 7-aminocephalosporanic acid and MMTA can be improved. After the amide basic catalysts are used, the product quality of synthesized cefodizime acid can be guaranteed.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, in particular to a preparation method of cefodizime acid. Background technique [0002] Cefodizime acid Chinese name: [6R-[6-α,7-β(Z)]]-7-[[(2-amino-4-thiazolyl)-(methoxyimino)acetyl]amino] -3-[[[(5-carboxymethyl)-4-methyl-2-thiazolyl]thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0 ] Oct-2-ene-2-carboxylic acid, this product is the main raw material for the synthesis of the third-generation cephalosporin antibiotics - cefodizime sodium. [0003] Chinese patent CN101239985A discloses 7-aminocephalosporanic acid and 2-mercapto-4-methyl-5-thiazole acetic acid in organic solvents (acetonitrile, ether, dichloromethane or ethyl chloroacetate) and acidic catalyst (trifluorinated boron gas or boron trifluoride complex) under the conditions of reaction to generate compounds, and then with 2-cis-methoxyimino-2-(2-aminothiazol-4-yl)acetic acid-1-hydroxybenzotriazole Active esters are added in dichlor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/06
Inventor 郑庚修尹鹏杜涵月阴华栋司志超孙智源
Owner SHANDONG JINCHENG PHARMACEUTICAL GROUP CO LTD
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