(369g) Development of a Visible Light Photochemical Process for the Manufacture of API Intermediate

Identifying reactive and highly selective catalytic systems is a critical component of process development in the pharmaceutical industry.  Due to their ability to initiate a variety of organic transformations from low-energy visible light, photoredox catalysts are becoming powerful tools in chemical synthesis.  Because these reactions are driven by the photon flux into the reaction solution, reaction performance can be enhanced by operating in a continuous flow reactors where the surface area to volume ratio is considerably higher than traditional batch reactors.  Herein, we present the application and development a photochemical process for the production of an active pharmaceutical ingredient intermediate. 

An integrated flow reactor was fabricated from PFA tubing and developed to investigate the oxidation of an indoline using an Iridium-based photoredox catalyst and 405 nm LEDs.  Sensitivity to reaction parameters, such as stoichiometry and residence time, was explored in a material sparing manner.  Additional lab experiments focused on catalyst screening and impact on light source wavelength.  To understand the impact of scale up on the reaction performance, chemical actinometry techniques were employed to estimate the photon flux for tubular reactors of increasing diameter. Reaction results and actinometry results were used to scale the reaction up to commercial production capabilities.