Liquid/liquid heterogeneous reaction monitoring: Insights into biphasic Suzuki-Miyaura cross-coupling

Monitoring the reaction progress of biphasic reaction mixtures has long presented a significant challenge to modern analytical techniques. While a multitude of widely utilized chemical transformations have been performed under such conditions, in-line separation and analysis of each phase have not been possible, inhibiting detailed kinetic and mechanistic studies of these important processes. Herein, we disclose a novel sampling technology capable of accurately monitoring reaction progress in biphasic mixtures using online high-performance liquid chromatography (HPLC) and multinuclear flow nuclear magnetic resonance (NMR) spectroscopy. A biphasic sampling platform was developed to circulate a single phase of a biphasic reaction mixture for analysis using these techniques. The utility of this methodology was demonstrated through analysis of boronic acid distribution and speciation under basic conditions as well as for monitoring the reaction progress of a biphasic Suzuki-Miyaura cross-coupling.

• Yusuke Sato¹, Junliang Liu¹, Ikenna Edward Ndukwe², Maria Victoria Silva Elipe², Daniel J. Griffin³, James I. Murray^4,5, Jason E. Hein^1,5,6,7

• ¹Department of Chemistry, The University of British Columbia, Vancouver, BC V6T 1Z1, Canada
• ²Pivotal Attribute Sciences, Drug Substance Technologies, Amgen, Inc., Thousand Oaks, CA 91320, USA
• ³Pivotal and Commercial Synthetics, Drug Substance Technologies, Amgen, Inc., Cambridge, MA 02142, USA
• ⁴Pivotal and Commercial Synthetics, Drug Substance Technologies, Amgen, Inc., Thousand Oaks, CA 91320, USA
• ⁵Acceleration Consortium, University of Toronto, Toronto, ON, Canada
• ⁶Department of Chemistry, University of Bergen, Bergen, Norway

• Request a Brochure
• Request more Info
• Request a Quote