Method for synthesizing coarse salt of ceftriaxone sodium by phase transfer catalysis method

Abstract

The invention relates to a method for synthesizing coarse salt of ceftriaxone sodium, which comprises the following steps: (1) taking 7-aminoce-phalosporanic acid (7-ACA) and a triazine ring as raw materials, adopting boron trifluoride acetonitrile as a catalyst for carrying out electrophilic substitution and finally, preparing 7-ACT by a zymohydrolysis method at a proper pH value; and (2) putting the 7-ACT and AE-active ester into an organic phase, adding a phase transfer catalyst for carrying out an N-acidylating reaction, salifying and crystallizing to obtain the coarse salt of the ceftriaxone sodium. The invention prepares the 7-ACT by the zymohydrolysis method, avoids the generation of a side reaction, enhances the yield and enhances the product purity. The reaction is carried out in the organic phase by the phase transfer catalyst, a product is transferred to a water phase, the continuous contact with a reactant is avoided, the generation of impurities with large molecular weight is lowered, and the coarse salt of the ceftriaxone sodium with high purity and high yield is finally obtained.

Description

technical field [0001] The invention relates to a process method for synthesizing crude salt of ceftriaxone sodium by a phase transfer catalysis method, which belongs to the preparation method of heterocyclic compound antibiotics containing cephalosporins. 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 treatm...

AI Technical Summary

Problems solved by technology

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.