Ceftibuten: Development of a Commercial Process Based on Cephalosporin C. Part IV. Pilot-Plant Scale Electrochemical Reduction of 3-Acetoxymethyl-7(R)-glutaroylaminoceph-3-em-4-carboxylic Acid 1(S)-Oxide

Abstract

This contribution describes the operation of a pilot plant for the production of 3-exomethylene-7(R)-glutaroylaminocepham-4-carboxylic acid 1(S)-oxide (4a) by the electrochemical reduction of 3-acetoxymethyl-7(R)-glutaroylaminoceph-3-em-4-carboxylic acid 1(S)-oxide (3a). This conversion is a key step in a new process for the production of Ceftibuten (1). The scale-up of the electrochemical reduction was demonstrated using a commercial flow-cell. The use of a novel type of extended-area tin cathode, which had been shown on a laboratory scale to produce significant improvements in the process, was successfully implemented in an ICI FM21-SP commercial-scale electrochemical reactor. † Ceftibuten was discovered by Shionogi and Co. Ltd., Osaka, Japan, and licensed to Schering Plough Corporation, Kenilworth, New Jersey. The drug is manufactured by Shionogi.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…The use of a tin cathode was found to be optimal for this reaction; various reducible functionalities such as carboxylates, a β -lactam, and a sulfoxide were left unscathed. 666 …”

“…The use of a tin cathode was found to be optimal for this reaction; various reducible functionalities such as carboxylates, a β-lactam, and a sulfoxide were left unscathed. 666 The direct electrochemical reduction of aromatic systems is conceivably difficult owing to arenes' electron-rich nature. Nevertheless, early efforts demonstrated that electrochemical conditions could be utilized to generate solvated electrons which could, in turn, enable the Birch reduction of aromatic systems.…”

Organic Electrosynthesis: Applications in Complex Molecule Synthesis

“…Cathodic reduction of an allylic acetate as a key step in the synthesis of the antibiotic ceftibuten ( 214 ) was reported by Walker and coworkers (Scheme ) . The transformation was performed on large scale in a pilot‐plant using a flow‐cell setup.…”

Characterization of the reaction environment in a filter-press redox flow reactor

“…Reasonable rates of mass transport and good flow dispersion can be realised with this geometry, which also facilitates modular expansion and predictable scale-up [5,6]. The parallel plate cell configuration is widely used in many large-scale electrochemical processes, such as the production of chlorine and caustic soda, adiponitrile and pharmaceuticals [3,7,8].…”