Synthetic method of ceftriaxone sodium crude salt

Abstract

The invention belongs to the field of chemical synthesis, and particularly relates to a synthetic method of a ceftriaxone sodium crude salt. The method comprises the following steps of: (1) performing electrophilic substitution on 7-ACA and a triazine ring by taking a BF3-acetonitrile solution as a catalyst to obtain 7-ACT at last; and (2) undergoing an N-acylation reaction on 7-ACT and AE-active ester in an organic phase, adding sodium iso-octoate, and undergoing a salt forming reaction to obtain the ceftriaxone sodium crude salt. The method is characterized in that: the 7-ACT is prepared with an enzymatic hydrolysis method after electrophilic substitution in the step (1); and a flocculating agent is added after the N-acylation reaction is completed in the step (2). The method has the advantages that: the product yield and purity are raised; the 7-ACT is prepared with the enzymatic hydrolysis method in the first step, and the enzymatic hydrolysis method has the characteristics of specificity and high efficiency, so that side reactions are avoided, the yield is increased by over 8 percent, and can be up to 88 percent, and the product purity is raised; and the flocculating agent is added in the second step, so that insoluble matters in a reaction liquid are removed, and a high-purity ceftriaxone sodium crude salt is obtained finally.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a synthesis method of ceftriaxone sodium crude salt. Background technique [0002] Ceftriaxone sodium is a semi-synthetic third-generation cephalosporin, which has a bactericidal effect on many Gram-positive bacteria, Gram-negative bacteria and anaerobic bacteria, and is most β-lactamase produced by bacteria (penicillinase and cephalosporinase) are highly stable, thereby enhancing their antibacterial effect. It is widely used clinically for respiratory tract infection, urinary tract infection (including pyelonephritis and gonorrhea), abdominal infection, pelvic infection, biliary tract infection, gastrointestinal infection, burn infection, wound infection, postoperative infection caused by bacteria sensitive to it And the prevention of infection during operation, the treatment of skin tissue infection, bone and joint infection, sepsis, meningitis, etc., has been use...

AI Technical Summary

Problems solved by technology

[0005] For the reported synthetic methods, there are disadvantages of high cost of raw materials, harsh reaction conditions, and long reaction time, which are not conducive to continuous and large-scale industrial production.

The yield of the first step is low, and the reaction conditions are harsh. First, the reaction is performed in an anhydrous system, and then hydrolyzed to generate 7-ACT, which is prone to side reactions

In the second step, the product and the reactant cannot be separated in time during the reaction, causing side reactions such as excessive condensation, resulting in the formation of large molecular weight impurities, and making the finished product unqualified in terms of optical rotation and color.

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