Cefdinir synthesis

Cephalosporins Have a nucleus that is similar to that of (3-lactams and similarly dismpt the synthesis of the peptidoglycan layer. This layer is important in maintaining cell wall integrity in gram-positive bacteria. Omnicef (Cefdinir) Cefzil (Cefprozil) Cephalexin (Keflex) Bioavailabihty is dose dependent is only about 16-21%. About 90% is excreted as the parent compound. It is well absorbed by the body and 90% of the dmg is excreted unchanged. 

The synthesis of the vinyl antibiotic cefdinir, which starts with the preformed unsaturated nucleus (30-2), illustrates a scheme that builds the almost obligatory aminothiazole in situ as the last step. Acylation of the amino group in (30-2) with 3-bromoacetoacetic acid (30-1) leads to the amide (30-3). Reaction of that intermediate with sodium nitrite proceeds on the activated methylene to form the nitrite as the initial product. This spontaneously tautomerizes to the observed oxime (30-4). Treatment with thiourea, in one of the standard procedures for forming thiazoles, then leads to (30-5). There is thus obtained cefdinir (30-5) [36]. 

Synthesis of 7(3-[2-(2-aminothiazol-4-yl)-2-(Z)-(trytiloxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid x p-toluenesulfonic acid x 2 N,N-dimethylacetamide (the precursor of Cefdinir) was described in Patent US 6,093,814. 

Another application of the Hantzsch method is in the synthesis of the aminothiazole coupling partner in the synthesis of the antibiotic cefdinir. The reactive methylene carbon of ethyl acetoacetate is first functionalized to the oxime after which a-chlorination is brought about to furnish the chloro-oxime substrate for Hantzsch synthesis with thiourea. A,jV-Dimethyl aniline is used as a base in the thiazole formation. ... 

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