First Example of a Continuous-Flow Carbonylation Reaction Using Aryl Formates as CO Precursors

    • Nerea Alonso1,3
    • Juan de Muñoz1
    • Brecht Egle2
    • Johannes L. Vrijdag2
    • Wim M. De Borggraeve2
    • Antonio de la Hoz3
    • Angel Díaz-Ortiz3
    • Jesús Alcázar1
    • 1Janssen Research and Development, Janssen-Cilag Department of Medicinal Chemistry S.A., Toledo, Spain
    • 2Molecular Design and Synthesis University of Leuven, Department of Chemistry, Heverlee Belgium
    • 3Universidad de Castilla-La Mancha Facultad de Ciencias y Tecnologías Químicas Real, Spain

    The first continuous flow carbonylation reaction using aryl formates as CO precursor is reported. The reaction is practical, scalable and high yielding. The use of a flow protocol safely allows expanding the scope to activated chlorides, nitrogen heterocycles and to the selective introduction of an ester group in dihalo-derivatives. Further selective reduction of the ester formed to an aldehyde in flow is also described.

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