Preparation method of cefamedin acid tris-intermediate

Abstract

The invention relates to a preparation method of a cefamedin acid tris-intermediate. According to the preparation method, by the adoption of a concentrated sulfuric acid catalysis method, the dangerousness of the reaction process is lowered, and the safety and smoothness of a reaction are guaranteed; through optimized hydrolysis reaction operation, the product processing technology is simplified while the reaction yield is significantly increased and the product quality is significantly improved. Thus, the preparation method is suitable for large-scale industrial production. The obtained cefamedin acid tris-intermediate is high in content and purity and can be directly used for preparing high-quality cefazolin antibacterial medicine as a production raw material.

Description

technical field [0001] The invention relates to a preparation method of a cefazolin compound intermediate, in particular to a preparation method of a cefazolin acid three-position intermediate. Background technique [0002] Cefazolin acid, also known as cefazolin, chemical name is (6R,7R)‐3‐[(5‐methyl‐1,3,4‐thiadiazol‐2‐yl)thiomethyl]‐8‐ Oxo‐7‐[[2‐(tetrazol‐1‐yl)acetyl]amino]‐5‐thia‐1‐azabicyclo[4.2.0]oct‐2‐ene‐2‐carboxylic acid, the first The semi-synthetic cephalosporin is the first generation of cephalosporin antibiotics widely used clinically at home and abroad. It is suitable for respiratory tract, urethra, pneumonia, cholecystitis, liver abscess, peritonitis, and pelvic inflammatory disease caused by sensitive bacteria. , Endocarditis, otitis media, sepsis and soft tissue infection. [0003] The preparation of cefazolin usually adopts 7-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid (abbreviated as 7-ACA) as raw material, by substituting the 3-position (3-acetyl 2...

AI Technical Summary

Problems solved by technology

Wherein, the weak base catalysis method generally uses water as the reaction solvent, and organic base or inorganic base is the catalyst, but because the base has a certain damage effect to the β-lactam ring in the cephalosporin nucleus in the aqueous solution, the yield is reduced, and the yield is reduced. The rate is generally 60-70%, and the product has high impurity content

Boron trichloride catalytic method, because boron trifluoride can play a protective role to the C‐7 amino group in the reaction, and increases the ionic strength in the reaction system, which is conducive to the progress of the reaction, improves the reaction yield, and can reach 85-92%, which is a commonly used process at present, but because boron trifluoride is immediately hydrolyzed in contact with moisture to generate highly toxic fluoride fumes, which are volatile, corrosive and toxic, so boron trifluoride solid complexes In the preparation process, there are large pollution, high energy consumption, large amount of waste liquid, and great safety risks in the process of preparation, transportation and use

Concentrated sulfuric acid catalytic method, the catalysts used include concentrated sulfuric acid and chlorophosphoric acid, the yield is relatively high, generally 75-80%, but due to the troublesome post-processing, it is rarely used at present

Iodotrimethylsilane catalyzed method has a short reaction time, but the yield is low, generally 45-50%, and the iodotrimethylsilane used is expensive, so it is not suitable for industrial production