Ceftibuten:: Development of a commercial process based on cephalosporin C.: Part II.: Process for the manufacture of 3-exomethylene-7(R)-glutaroylaminocepham-4-carboxylic acid 1(S)-oxide

Analysis of several options for the synthesis of Ceftibuten from cephalosporin C-derived starting materials led to the conclusion that the most practical option, leading to the lowest costs, would be realized by trying to resurrect the previously discarded electrochemical reduction process. This contribution describes the preparation of 3-exomethylene-7(R)-glutaroylaminocepham-4-carboxylic acid 1(S)-oxide (10,1(S)-oxide) in almost quantitative yield by the electrochemical reduction of 3-acetoxymethyl-7(R)-glutaroylaminoceph-3-em-4-carboxylic acid l(S)-oxide (9,1(S)-oxide) using a high-surface area tin mesh cathode. The new product has been shown (see Bernasconi, E.; Lee, J.; Sogli, L.; Walker, D. Org. Process Res. Dev. 2002, 6, 169) to be a superior new intermediate for the preparation of orally active cephalosporins; such as Ceftibuten.