Method for preparing cefixime compound

A technology of cefixime and cefixime methyl ester, which is applied in the field of preparation of cefixime compounds, can solve the problems of harsh reaction conditions, expensive solvents, unfavorable continuity, etc., and achieve increased product yield, increased yield and Purity, the effect of shortening the production cycle

Inactive Publication Date: 2013-12-25
TIANJIN UNIVERSITY OF TECHNOLOGY
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  • Abstract
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Problems solved by technology

[0010] It can be seen from the above preparation method that THF is used in this process, and the solvent is expensive and difficult to recover, and the mother liquor after crystallization and centrifugation of cefixime methyl ester (MFCEF) will take away part of the material, affecting the yield; Synthesis of cefixime methyl ester (MFFCEF) will generate a by-product 2-mercapto

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  • Method for preparing cefixime compound
  • Method for preparing cefixime compound
  • Method for preparing cefixime compound

Examples

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Example Embodiment

[0031] Example 1:

[0032] A preparation method of cefixime compound, the steps are as follows:

[0033] 1) Add 300mL of dichloromethane, 45mL of ethanol, 15mL of purified water to a 1000mL four-neck flask, stir and cool to 0-2℃, add 50g of 7-AVCA, 100g of MICA active ester, and slowly add triethyl dropwise at 5℃ It takes about 0.5 hours for 25g of amine. After the addition, the temperature is raised to 5-10°C, and the reaction is carried out for 5 hours under these conditions. The pH is controlled at 7.5-8.0. The 7-AVCA in the reaction solution is detected by HPLC. When <0.5wt%, the reaction is stopped, and a solution of cefixime methyl ester is prepared.

[0034] 2) Add 150 mL of purified water to the above-mentioned cefixime methyl ester solution, stir for 10 minutes, stand still to separate the water phase, and then extract the organic phase twice with 150 mL of purified water, combine the water phases, add 1g sodium silicate and 1g ethylenediamine Tetraacetic acid and 5 g activ...

Example Embodiment

[0038] Example 2:

[0039] The steps of the preparation method of a cefixime compound are as follows:

[0040] 1) In a 1000mL four-neck flask, add 350mL of chloroform, 60mL of methanol, 25mL of purified water, stir and cool to 0-5℃, add 50g of 7-AVCA, 120g of MICA active ester, and slowly drop 28g of triethylamine at 5℃ About 1 hour, after the addition, the temperature is raised to 8-12°C, and the reaction is conducted for 5.5 hours under this condition, the pH is controlled at 7.5-8.0, and the 7-AVCA in the reaction solution is detected by HPLC <0.5% stop the reaction and prepare a solution of cefixime methyl ester.

[0041] 2) Add 200 mL of purified water to the above cefixime methyl ester solution, stir for 10 minutes, and stand still to separate the water phase. The organic phase was extracted twice with 100 mL of purified water. The aqueous phases were combined, 0.5 g of sodium hydroxide and 0.5 g of ethylenediamine tetraacetic acid, 2.5 g of activated carbon were decolorized a...

Example Embodiment

[0044] Example 3:

[0045] A preparation method of cefixime compound, the steps are as follows:

[0046] 1) Add 300 mL of ethyl acetate, 50 mL of methanol, and 30 mL of purified water to a 1000 mL four-neck flask, stir and cool to 5-8°C, add 50 g of 7-AVCA, 125 g of MICA active ester, and slowly add 25 g of cyclohexylamine at 5°C. Approximately 0.5 hours, after the addition, the temperature was raised to 10-15°C, and reacted for 6 hours under these conditions, the pH was controlled at 8.0-8.5, and the 7-AVCA in the reaction solution was detected by HPLC <0.5% stop the reaction and prepare a solution of cefixime methyl ester.

[0047] 2) After the reaction, add 150 mL of purified water, stir for 10 minutes, and stand still to separate the water phase. The organic phase was extracted twice with 150 mL of purified water. The aqueous phases were combined, 1.5 g of sodium hydroxide and 1.5 g of ethylene diamine tetraacetic acid, 5 g of activated carbon were decolorized at room temperatur...

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Abstract

The invention provides a method for preparing a cefixime compound. According to the method for preparing the cefixime compound, 7-AVCA is used as a raw material, cefixime methyl ester is obtained through action of the 7-AVCA and MICA active ester by means of an acylation reaction on 7-amno of the 7-AVCA, the cefixime methyl ester is not separated, inorganic base hydrolysis and a refining reaction are directly conducted on the cefixime methy ester, and therefore cefixime is obtained. The method for preparing the cefixime compound has the advantages that original expensive reagents such as tetrahydrofuran difficult to recycle are replaced by an organic solvent, the organic solvent and water are immiscible, the reaction solvent is easy to recycle and reuse, the pollution to the environment is reduced, and the production cost is reduced; acylation and hydrolysis are integrated, operation is simplified, the production period is shortened, the yield and the purity are improved, and large-scale industrial production is facilitated.

Description

technical field [0001] The invention relates to medicine synthesis technology, in particular to a preparation method of cefixime compound. Background technique [0002] Cefixime is the third-generation oral cephalosporin, first developed and marketed by Fujisawa Pharmaceutical Co., Ltd., Japan, and approved by the US FDA in 1987. It has been widely clinically used in more than 80 countries, mainly for sensitive bacteria Respiratory tract infection, urinary tract infection, meningitis, ENT infection, biliary tract infection, pyelonephritis, etc. The cefixime compound has a broad antibacterial spectrum, and has good antibacterial activity against most Enterobacteriaceae bacteria such as Streptococcus pyogenes, Pneumococcus, Streptococcus agalactiae, Neisseria gonorrhoeae, Influenza bacilli, Morakata, Escherichia coli, and Klebsiella pneumoniae. The commonly used production process is to use 7-amino-3-vinyl-cephalosporanic acid (7-AVCA) to acylate the side chain acid active e...

Claims

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Application Information

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IPC IPC(8): C07D501/22C07D501/04C07D501/06
Inventor 刘金彪黄磊孙永跃
Owner TIANJIN UNIVERSITY OF TECHNOLOGY
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