The Synthesis of GV143253A: A Case Study for the Use of Analytical and Statistical Tools to Elucidate the Reaction Mechanism and to Optimize the Process

GV143253A 1 is a broad-spectrum injectable β-lactam belonging to the class of trinem antibiotics. This article describes the work which enabled a detailed process understanding via several analytical techniques and the subsequent optimization of a key intermediate. By means of a combined application of 31P NMR spectroscopy and MS spectrometry, the main impurities have been identified and the reaction mechanisms clarified. Moreover, a design of experiments (DoE) approach was applied which substantially improved the overall yield.