Method for preparing sodium 7-methoxy-7-chloracetylamino-3-methyltetrazole sulfidomethyl cephalosporanic acid

Abstract

The invention discloses a preparation method for 7-methoxy-7-chloracetyl amido-3-methyl tetrazole s-methyl sodium cephalosporanic acid. The method comprises the following steps: adding 7-methoxy-7-chloracetyl amido-3-methyl tetrazole s-methyl cephalosporanic acid benzyl ester and trifluoroacetic acid in turn into the phenolic compound solvent for reaction; adding ethyl acetate into the reaction liquor when the reaction residue is less than 1 percent; adjusting the pH value of the reaction liquor to form an organic phase and a water phase; taking the water phase and adding ethyl acetate into the water phase; after even mixing, regulating the pH value, splitting phases through standing, collecting the organic phase after extraction, and then carrying out concentration and drying; adding theorganic phase into ethanol isopropyl alcohol mixed liquor; stirring to dissolve the organic phase, adding sodium iso-octoate and isopropyl alcohol mixed liquor into the mixed solution for reaction; cooling, filtrating and drying the product after the reaction to obtain the finished product. The method saves the preparation process of adopting an alchlor catalyst; and simultaneously trifluoroacetic acid is added into the solvent of o-cresol, m-cresol or p-cresol for benzyl ester removing hydrolysis, thereby not only shortening the technical flow and simplifying the operation, but also improving the yield to 75 to 80 percent.

Description

technical field [0001] The present invention relates to pharmaceutical and chemical intermediates, in particular to a preparation method of 7-methoxy-7-chloroacetamido-3-methyltetrazolium thiomethyl cephalosporanic acid sodium, which is the mother nucleus of the third-generation antibiotic cefminox sodium medicine . technical background [0002] 7-methoxy-7-chloroacetamido-3-methyltetrazolium thiomethyl cephalosporanic acid sodium is the mother nucleus of synthetic cefminox, cefminox sodium is the third generation of cephalosporin antibiotics, this product and β-endo Penicillin-binding protein has a strong affinity, can inhibit the biosynthesis of cell wall, and can bind to peptidoglycan, inhibit the combination of peptidoglycan and lipoprotein and promote bacteriolysis. In addition, this product can also combine with the diaminopimelic acid of the outer membrane lipoprotein unique to Gram-negative bacteria, showing its strong double bactericidal effect in a short time. Ce...

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Problems solved by technology

But the anhydrous aluminum trichloride used in this reaction process is very easy to absorb moisture and deteriorate. After the main reaction is finished, excessive aluminum trichloride needs to be hydrolyzed. Heat is released in the hydrolysis process, and the temperature is difficult to control. The aluminum salt formed causes decomposition. Layer difficulty, post-treatment is more complicated, is unfavorable for industrial production, and the weight yield of cefminox sodium is only 68~71%

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