Scalable Continuous Flow Hydrogenation of Isoquinoline in Trickle-Bed Reactors

A robust and scalable continuous-flow hydrogenation process was developed for the synthesis of 1,2,3,4-tetrahydroisoquinoline (THIQ) scaffold using a commercially available heterogeneous Pt/Al2O3 catalyst in a trickle-bed reactor. This study outlines the systematic selection of catalysts and solvents as well as process optimization using the Design of Experiments (DoE). A scale-up run was successfully demonstrated at a 13 kg scale of THIQ with a 99% isolated yield in pilot equipment. This work demonstrates a practical strategy for the continuous-flow synthesis of THIQ, highlighting its potential for industrial.