A novel green approach to the synthesis of Etoricoxib

Within the framework of the ecological transition towards sustainable development, chemical sciences play a fundamental role. Development of alternative synthetic reaction schemes to control environmental hazards and pollution, which were the result of the traditional synthesis represents one the principal milestone of this transition. To date, the optimization of reported processes, aiming to satisfy the quest of maximum yield in an environmentally respectful frame, requires a radical change in the approach of chemicals production. To support this transition to 'greener' synthesis of compounds, a variety of green metrics capable to assess the environmental performance and impact of chemical processes have been developed starting from the twelve principles of green chemistry. In this context, we report on a preliminary eco-optimization study of the synthesis of the non-steroidal anti-inflammatory drug Etoricoxib. We comparatively analysed several reported synthetic routes considering both the overall yield and the number of synthetic steps required. For the synthetic route identified as the most promising one, showing only two consecutive Suzuki reactions, sequential improvements in terms of greenness have been performed. In the pharmaceutical research area, reaction solvents and purification processes are the most environmentally impactful parts.2 Hence, alongside to the optimization of reaction parameters such as temperature and reaction time using unconventional heating methods, the effect of 'green' solvents, able to promote the reaction and facilitate product recovery at the same time, was evaluated. Finally, the environmental performance of the optimized route was preliminarily assessed using green metrics.