502. Highly Productive Flow Synthesis for Lithiation, Borylation, and/or Suzuki Coupling Reaction

Hiroki Soutome, Kei Maekawa, Yosuke Ashikari, and Aiichiro Nagaki, OPR&D, (2024), DOI: 10.1021/acs.oprd.4c00021

The efficient synthesis of aromatic boronic acids was achieved by increasing the concentration, flow rate, and mixer diameter to prevent clogging. A 1 h synthesis actually produced 180 g of boronic acid. The real-time analysis of the reaction solution was investigated using in-line analyzers suitable for high flow rates. Additives were also studied to accelerate the Suzuki coupling reaction of the boronic acids. Integrated one-flow reactions combining boronic acid synthesis and Suzuki coupling produced pharmaceutical precursors in 97−143 s.