Synthesis of a spiroketone intermediate featuring a green and sustainable telescoped flow process

Abstract

A telescoped flow process was implemented for synthesizing a chiral spiroketone, a pivotal building block of several active pharmaceutical ingredients. This process combined a ring closing metathesis step and a hydrogenation step using one single catalyst (Hoveyda–Grubbs 2nd generation catalyst). This innovative approach offers substantial benefits including cost savings, enhanced throughput with adaptable demo-scale devices, real-time reaction monitoring via process analytical technology, elimination of laborious intermediate separation, decreased process mass intensity, and streamlined unit operations. Notably, the developed telescoped flow process utilizes one single catalyst with a significantly reduced loading, resulting in a remarkable 70% saving on process cost and a 60% decrease in PMI compared to the original batch procedure.