Sustainable one-pot synthesis of a mirabegron advanced intermediate avoiding isolation of potentially genotoxic intermediates and reducing hazardous reagents

Abstract A sustainable one-pot process for the synthesis of an advanced intermediate of Mirabegron is described. The developed methodology eliminates the isolation of genotoxic intermediates, minimizes solvent usage and avoids the use of hazardous reagents. The process integrates esterification, reductive amination, and nitro reduction into a single reaction pot, thereby simplifying manufacturing operations and improving the process safety. The optimized process affords the advanced intermediate in good overall yield and excellent HPLC purity. Compared with previously reported approaches, the developed route significantly reduced processing steps, solvent consumption, batch cycle time and operational hazards. The strategy represents a greener, safer, cost-effective and industrially viable approach for the large-scale manufacture of Mirabegron intermediate.