Efficient procedure for c '- 3 substitution and c - 7 n-acylation of 7-aminocepha-losporanic acid (7-aca): Synthesis of cefazolin antibiotic and related compounds

A new preparative method for the C'-3 substitution of 7-aminocepha-losporanic acid (7-ACA), is described. The key feature of our method is based on the protection of the anino group as a Schiff base instead of the usual procedure based on the acylation of the amino group. The relative incapacity of 7-ACA derivatives to produce organic solutions with usual tertiary bases is easily overcome with bicyclic amidines. Catalytic amounts of these bases and N-trimethylsilyl-2-oxazolidinone are used to obtain the silylated products. Activation of sensitive tetrazolylacetic acid by means of N,N-dimethylchloro-sulfitemethaniminium chloride (SOCl₂-DMF) and preparation of cefazolin antibiotic under anhydrous conditions is also described.