Autonomous closed-loop photochemical reaction optimization for the synthesis of various angiotensin II receptor blocker molecules†

Abstract

Optimization is gaining huge attention in industries like pharmaceuticals, fine chemicals, and petrochemicals to maximize reaction yield, minimize waste, and improve process efficiency. Optimization is keeping pace with variations in multiple reaction conditions and sustaining a shift from laboratories to industries. Herein, we report an integrated continuous flow reactor platform with Bayesian optimization (BO)-assisted reaction optimization that can autonomously explore the optimal conditions for photochemical bromination reactions of biologically active sartan intermediates. Further, the controlled optimized parameter is extended towards the efficient solar light utility for bromination reactions, and the reaction is achieved in a residence time of 32 sec with an excellent space–time yield of 7 kg L⁻¹ h⁻¹. The individual photobromination and nucleophilic substitution steps for sartan intermediate synthesis smoothly transitioned from the mg h⁻¹ to kg h⁻¹ production. In addition, autonomously explored bromination conditions are integrated with continuous flow tools for synthesizing, extracting, and purifying the angiotensin II receptor blocker intermediate within only 7.2 min.