Preparation process of cefamandole nafate

Abstract

The invention discloses a preparation process of cefamandole nafate. The preparation process comprises steps of: heating and stirring 7-amino cephalosporanic acid, 5-mercapto-1-methyltetrazole and a catalyst boron trifluoride acetonitrile complex for a reaction; and carrying out a cooling post-treatment to obtain cefditoren nuclear parent; conducting a heating reflux reaction on the cefditoren nuclear parent and a silanizing agent until the solution turns to a clarified state; adding N, N-dimethyl aniline under the protection of inert gas at a low temperature, dropwise adding D-(-)-O-formyl mandeloyl chloride for reaction, and carrying out post-treatment to obtain formyl cefamandole acid; and reacting the formyl cefamandole acid with an organic acid salt, and recrystallizing to obtain the cefamandole nafate. By the above way, the preparation process of cefamandole nafate provided by the invention employs a simple and easily implemented process to obtain high-yield cefditoren nuclear parent with low impurity content; dichloromethane is used as a solvent to obtain the cefamandole acid with greatly enhanced color grade and yield; and dosage of activated carbon in the post-treatment is obviously reduced, so as to reduce the production cost.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation process of cefamandole sodium. Background technique [0002] Cefamandole sodium, also known as ceftriaxone, is a second-generation cephalosporin that is positive for Gram-negative bacteria, meningococcus, Clostridium anaerobes, Neisseria gonorrhoeae, Klebsiella pneumoniae, Escherichia coli, and indole Proteus and influenza bacilli have strong effects, especially for Haemophilus cefamandole sodium is the most effective. Clinically, cefamandole sodium is mainly used for various infections caused by sensitive bacteria, such as respiratory tract infection, pyelonephritis, biliary tract infection, peritonitis, urinary tract infection, sepsis and skin soft tissue, joint, bone and other infections. [0003] At present, the preparation technology of cefamandole sodium mainly includes three kinds of synthetic routes: the first is to synthesize cefamandole sodium by taking 7-aminocep...

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Problems solved by technology

[0003] At present, the preparation technology of cefamandole sodium mainly includes three kinds of synthetic routes: the first is to synthesize cefamandole sodium by taking 7-aminocephalosporanic acid as raw material and active ester; The raw material reacts with active esters to obtain cefamandole acid, and then produces cefamandole sodium through a salt-forming reaction. Traditionally, dicyclohexylcarbodiimide and other allergic and toxic substances are used in the process , and the total yield is not high; the 3rd is to obtain cefamandole sodium by acylation reaction with cefditoren mother nucleus as raw material, adopt mixed solvent to be difficult for reclaiming in the reaction process, also have and adopt ethyl acetate to react, but the obtained The fineness of cefamandole sodium is not good, and a large amount of activated carbon is needed for decolorization, which increases the production cost

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