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

A phase transfer catalysis method, the technology of ceftriaxone sodium, which is applied in chemical instruments and methods, physical/chemical process catalysts, organic compounds/hydrides/coordination complex catalysts, etc., can solve the problem that products and reactants cannot be separated in time , the optical rotation of finished products, unqualified color and harsh reaction conditions, etc., to achieve the effect of highlighting substantive characteristics, improving product yield, and improving reaction conversion rate

Active Publication Date: 2010-06-23
YIYUAN XINQUAN CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] 1. Synthesis of 7-ACT

[0029] According to the preparation steps of the comparative example, after adding purified water, solid-phase carboxypeptidase Alg was added, and the pH was constantly adjusted to 2.0 to 2.5 with 5% (volume fraction) of ammonia water until the pH was stable, and the crystallization procedure was also the same as that of the comparative example. After drying, 23.79 g of dry product was obtained, the purity (HPLC) was 99.25%, and the molar yield was 85% [n(7-ACT) / n(7-ACA)×100%].

[0030] 2, the synthesis of ceftriaxone sodium coarse salt

[0031] According to the preparation steps of the comparative example, 138 mL of mixed solvent [V (water): V (dichloromethane) = 1: 2], 2 g of immobilized PEG-800, 22 g (58.67 mmol) of 7-ACT were added to the three-necked flask, Appropriate amount of triethylamine until the reaction solution is alkaline, after dissolution, add 21g (59mmol) of AE active ester to maintain at about 5°C, stir for 4h, then add 78mL o...

Embodiment 2

[0033] 1. Synthesis of 7-ACT

[0034] According to the preparation steps of the comparative example, after adding purified water, 1.5 g of carboxypeptidase A was added, and the pH was constantly adjusted to 2.0 to 2.5 with 5% (volume fraction) of ammonia water until the pH was stable, and the crystallization procedure was also the same as that of the comparative example. After drying, 24.64 g of dry product was obtained, the purity (HPLC) was 99.25%, and the molar yield was 88% [n(72ACT) / n(7--ACA)×100%].

[0035] 2, the synthesis of ceftriaxone sodium coarse salt

[0036]According to the preparation steps of the comparative example, 138 mL of mixed solvent [V (water): V (dichloromethane) = 1: 2], 2.2 g of immobilized PEG-800, 22 g of 7-ACT (58.67 mmol) were added to the three-necked flask , an appropriate amount of triethylamine until the reaction solution is alkaline, after dissolving, add 21g (59mmol) of AE active ester to maintain about 5°C, stir and react for 4h, then add...

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PUM

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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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/06B01J31/06A61P31/04C12P35/00
Inventor 周红燕周磊李敬涛
Owner YIYUAN XINQUAN CHEM
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