Application of PAT Tools for the Safe and Reliable Production of a Dihydro-1<i>H</i>-imidazole

Abstract

The application of two Process Analytical Technology (PAT) tools was studied and implemented for the safe and reliable synthesis of an advanced intermediate (<b>4<i>S</i>,5<i>R</i>-7</b>) of a member of the dihydro-1<i>H</i>-imidazole (<b>1</b>) class of compounds. Real time data were generated using ReactIR to track the complete breakdown of phosgene precursors (<b>2</b>) to phosgene (<b>3</b>) and confirm the absence of these hazardous materials prior to batch transfer operations. In addition, the chiral resolution by crystallization of <i><b>rac</b></i> <b>7</b> was monitored by a Lasentec FBRM probe-based system. Implementation of the latter helped to track the crystallization process to minimize the risk of cocrystallization of undesired isomer <b>4<i>R</i>,5<i>S</i>-7</b>