(610d) Synthesis of a Spiroketone API Intermediate Featuring a Green and Sustainable Telescoped Flow Process

The fast-growing demand for efficient and robust synthesis approaches of new chemical entities for active pharmaceutical ingredients (APIs) and their intermediates has seen a rapid development in continuous processing. In a recent drug development endeavor at Boehringer Ingelheim, our focus was on synthesizing a chiral spiroketone as a pivotal building block. We explored both batch and continuous procedures and successfully developed and implemented a telescoped flow process for spiroketone synthesis. This innovative approach offers substantial benefits including energy and cost savings, enhanced throughput with adaptable small-scale devices, real-time reaction monitoring via process analytical technology (PAT), elimination of laborious starting material purification and intermediate separation, reduced Process Mass Intensity (PMI), and streamlined unit operations. Moreover, by transitioning to larger reactors, this process can be readily scaled up to meet manufacturing demands, ensuring excellent transferability to large-scale production. Notably, the developed telescoped flow process reduces catalyst and solvent usage compared to the original batch procedure, resulting in a remarkable 70% reduction in catalyst cost and a 60% decrease in PMI.