Flow Synthesis of 2‐[Methyl(pyridin‐2‐yl)amino]ethanol: An Experimental and Computational Study

Abstract

AbstractMicroreactor technology is increasingly applied in the chemical‐pharmaceutical industry for safer and more efficient drug production as compared to the traditional batch process. This technology is employed for the first time to study the production of 2‐[methyl(pyridin‐2‐yl)amino]ethanol, the first intermediate in rosiglitazone synthesis. Under the optimum operating conditions, a single microreactor chip at 160 °C allowed to produce the equivalent of more than five batch reactors at 120 °C. The kinetic study indicated that the reaction is second order. Thermodynamic parameters were determined by the Eyring equation and density functional theory (DFT) calculations with good agreement. DFT results suggested a concerted nucleophilic aromatic substitution reaction mechanism.