Study On The Synthesis Of Cefdinir Bulk Drugs

The development and mechanism of antibiotic agents were introduced briefly in thispaper. Cefdinir, one of the third-generation cephalosprins, was described in detail,including its antibiotic mechanism, pharmacological properties, clinical effects and ralatedsynthetic methods. The synthetic process of cefdinir and actived thioester was researched.After investigation of a series of synthetic routes of cefdinir, we determined the best routeand researched each step of the synthetic process for the goal of cost-cut, simplifyingoperation procedure and improving yield.The synthesis of2-Benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-acetoxyiminothioacetate was studied, which was an important intermediate of cefdinir. Acetylation of(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetic acid, which was prepared by hydrolysisof its ester, with acetyloxide gave (Z)-2-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid.Treatment of it with triethylamine gave the correspoding salt. The activated sulfer ester,2-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-acetoxyiminothioacetate, was obtained bycondensation reaction of the corrspoding triethylamine salt with the accelerating agentbis(2-mercaptobenzothiazolyl) disulfide in dichloromethane in the presence of triphenyl-phosphine. The total yield was56.6%and the purity of the product was higher than98.5%(HPLC).Reaction of2-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-acetoxyiminothioacetatewith7-amino-3-vinyl-3-cephem-4-carboxylic acid(7-AVCA) in the mixture of tetrahydrofuran and water gave acetoxy blocking Cefdinir, and then cleavaging the acetoxy groupby using ammonium and potasium carbonate solution without seperation. Acidation ofthe reaction solution to give the crude cefdinir, which was treated by phosphoric acid inthe presence of acetonitrile, gave the crystal salt of cefdinir and phosphoric acid. Cefdinirwas obtained by purification of phosphoric acid salt of cefdinir with sodium bicarbonatein water. The total yield was over70%and the purity of was higher than99%(HPLC).The chemical structures of cefdinir had been characterized by means of IR and~1H-NMR. The product quality accords with the standard of Chinese pharmacopoeia.