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Continuous Flow Synthesis of Carbonylated Heterocycles via Pd-Catalyzed Oxidative Carbonylation Using CO and O2 at Elevated Temperatures and Pressures

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    Continuous Flow Synthesis of Carbonylated Heterocycles via Pd-Catalyzed Oxidative Carbonylation Using CO and O2 at Elevated Temperatures and Pressures
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    † Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, A-8010 Graz, Austria
    ‡ Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, Austria
    *E-mail: [email protected]
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    Organic Process Research & Development

    Cite this: Org. Process Res. Dev. 2017, 21, 7, 1080–1087
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    https://doi.org/10.1021/acs.oprd.7b00217
    Published June 28, 2017
    Copyright © 2017 American Chemical Society
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    Abstract

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    A continuous-flow Pd-catalyzed oxidative carbonylation protocol utilizing CO and O2 gas for the synthesis of carbonylated heterocycles is described. The optimization of temperature, pressure, CO/O2 ratio, catalyst loading, and reaction time resulted in process intensified conditions for this transformation. The optimized continuous flow conditions (120 °C, 20 bar pressure, 24 min residence time) were used to prepare a number of benzoxazolone, 2-benzoxazolidinone, and other biologically and synthetically important five- and six-membered carbonylated heterocycles in good overall yield and purity (14 examples). The continuous-flow process enables the safe and scalable oxidative carbonylation using CO/O2 under elevated pressures and temperatures.

    Copyright © 2017 American Chemical Society

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.oprd.7b00217.

    • More details of the microreactor setup, copies of 1H and 13C NMR spectra of all compounds and HPLC chromatograms of all chiral compounds (PDF)

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    Organic Process Research & Development

    Cite this: Org. Process Res. Dev. 2017, 21, 7, 1080–1087
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.oprd.7b00217
    Published June 28, 2017
    Copyright © 2017 American Chemical Society
    Request reuse permissions

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