Abstract

Automated Scalable Synthesis Enabled by High-Speed Circulation Flow

Wu Jie, Assistant Professor, Chemistry Department, National University of Singapore

Automated multistep synthesis of small organic molecules remains a formidable challenge, as conventional batch platforms are often limited by scalability, while continuous-flow systems face difficulties in handling solids, slow reactions, and compatibility across multiple steps. In this presentation, I will introduce a modular automated multistep synthesis platform built around high-speed circulating flow (HSCF) reactors that integrate the strengths of both batch and flow approaches. This architecture enables the direct adoption of literature-reported protocols across homogeneous, heterogeneous, and photochemical transformations for scalable multistep synthesis. Two platform configurations were demonstrated: an “all-in-one” setup enabling fully automated synthesis of brexpiprazole (>25 g) within a compact footprint, and an “integrated flow” platform facilitating the semi-continuous production of esonarimod and two benzoxazinone derivatives at rates exceeding 10 g/day. We establish a universal, scalable, and reconfigurable architecture that significantly advances automated multistep synthesis, offering a practical solution for the on-demand production of functional small molecules.