Method for preparing cefonicid dibenzylethylenediamine salt

A technology for cefnicid dibenzyl ethylene diamine salt and cefene, which is applied in the field of preparing cefonicid dibenzyl ethylene diamine salt, can solve the problems of poor product quality, long production cycle, low equipment and the like, and achieve high quality Good, the process conditions are realized, and the reaction process steps are simple.

Inactive Publication Date: 2012-10-31
GUANGDONG LIGUO PHARMACY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The technical problem to be solved by the present invention is to provide a method that can be used in the prior art for the defects of long production cycle, low pH value, serious corrosion of equipment, an...

Method used

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  • Method for preparing cefonicid dibenzylethylenediamine salt
  • Method for preparing cefonicid dibenzylethylenediamine salt
  • Method for preparing cefonicid dibenzylethylenediamine salt

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Effect test

Embodiment 1

[0031] The method for preparing cefnicillin dibenzylethylenediamine salt, comprises the following steps:

[0032] (1) Acylation: 13.5 g of 7-amino-3-[methylsulfonate-1-H-tetrazol-5-yl-mercaptomethyl]-3-cephem-4-carboxylic acid, pure water Mix 100ml and 50ml of tetrahydrofuran in a reaction flask, cool down to 0°C, add 5ml of ammonia water with a concentration of 12.5% ​​by mass to dissolve and clarify, then add 7.2g of D-(-)-formylmandeloyl chloride dropwise, and add alkali during the reaction Maintain a pH value of 6.0, and add acylation reaction for 30 minutes;

[0033] (2), deformylation: respectively adopt 27ml dichloromethane to extract the reaction solution of step (1) acylation reaction twice, add 100ml methanol to the aqueous phase, cool to-30°C, then add mass percentage concentration of 20ml of 15% sodium hydroxide solution was reacted at -30°C for 60min.

[0034] (3) Salt formation: control step (2) The temperature of the reaction solution after the deformylation r...

Embodiment 2

[0036] The method for preparing cefnicillin dibenzylethylenediamine salt, comprises the following steps:

[0037] (1) Acylation: 13.5 g of 7-amino-3-[methylsulfonate-1-H-tetrazol-5-yl-mercaptomethyl]-3-cephem-4-carboxylic acid, pure water Mix 100ml and 50ml of tetrahydrofuran in a reaction flask, cool to 3°C, add 5ml of sodium hydroxide with a concentration of 10% by mass to dissolve and clarify, then add 7.2g of D-(-)-formylmandeloyl chloride dropwise, during the reaction Add alkali to maintain the pH value at 8.0, and add acylation reaction for 10 minutes;

[0038] (2), deformylation: respectively adopt 27ml dichloromethane to extract the reaction liquid of step (1) acylation reaction twice, add 100ml methanol to the aqueous phase, cool to-45°C, then add mass percent concentration of 20ml of 20% potassium hydroxide was reacted at -45°C for 120min.

[0039] (3), Salt formation: control step (2) The temperature of the reaction solution of the deformylation reaction is kept a...

Embodiment 3

[0041] The method for preparing cefnicillin dibenzylethylenediamine salt, comprises the following steps:

[0042] (1), acylation: 13.5 g of 7-amino-3-[methylsulfonate-1-H-tetrazol-5-yl-mercaptomethyl]-3-cephem-4-carboxylate, pure 100ml of water and 50ml of tetrahydrofuran were mixed in a reaction flask, cooled to 5°C, 6ml of sodium carbonate with a concentration of 15% by mass was dissolved and clarified, and then 7.2g of D-(-)-formylmandeloyl chloride was added dropwise. The alkali maintains the pH value at 7.0, and the acylation reaction is added for 35 minutes;

[0043](2), deformylation: respectively adopt 27ml dichloromethane to extract the reaction solution of step (1) acylation reaction twice, add 100ml methanol to the aqueous phase, cool to-35°C, then add mass percent concentration of 20ml of 15% mixed solution of sodium hydroxide and potassium hydroxide was reacted at -35°C for 100min.

[0044] (3), Salt formation: control step (2) The temperature of the reaction so...

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Abstract

The invention discloses a method for preparing a cefonicid dibenzylethylenediamine salt. The method comprises the following steps of: (1) adding an alkali into 7-ACA-3-SMT in water for dissolving, and reacting with D-(-)-formyl phenylacetyl chloride; (2) cooling a reaction liquid below 20 DEG C below zero, and adding an alkali for reacting; and (3) cooling the reaction liquid treated in the step (2), adding hydrochloric acid for adjusting the pH value, and reacting with N, N'-dibenzyl ethylenediamine diacetate to obtain a cefonicid dibenzylethylenediamine salt. The invention provides a method for preparing a cefonicid dibenzylethylenediamine salt, which has the advantages of low-temperature reaction, short reaction time, simple post-treatment and high product quality.

Description

technical field [0001] The invention belongs to the technical field of medicines, and relates to a preparation method of a drug intermediate, in particular to a method for preparing cefanixime dibenzylethylenediamine salt. Background technique [0002] Cefnicillin disodium is a second-generation cephalosporin, developed by Glaxo Smith Kline Company in the United Kingdom. The drug has anti-enterobacteriaceae and anti-Haemophilus influenzae activity, and is mainly used for the treatment and treatment of sensitive bacterial infections and Surgical infection prevention has a good application prospect because of its broad antibacterial spectrum, enzyme resistance, long half-life, and good safety. [0003] At present, there are mainly two synthetic routes for cefnixime sodium: (1) 7-D-mandelic acid amido cephalosporanic acid methyl ester and 5-mercapto-1,2,3,4-tetrazolium-1-methanol Sulphonic acid double sodium salt (SMT-DS for short) condensation reaction, decarboxylation, salt ...

Claims

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Application Information

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IPC IPC(8): C07D501/04C07D501/36C07C211/27C07C209/68
Inventor 周成光陈亦开
Owner GUANGDONG LIGUO PHARMACY
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