Fabio Lima - A Multistep Flow Process for the Synthesis of Highly Functionalized Benzoxazoles

Version 1

      Publication Details (including relevant citation   information):

      DOI : 10.1021/ol402706a

      Published on Web 10/22/2013

      ORGANIC LETTERS 2013

      Vol. 15, No. 21

      5546–5549

      Jörg Sedelmeier, Fabio Lima, Alain Litzler, Benjamin Martin and   Francesco Venturoni

      Abstract:

      An efficient and scalable transformation of 3-halo-N-acyl   anilines to the corresponding benzoxazoles within a continuous   flow reactor is reported. This transformation proceeds via   base-mediated deprotonation, ortho-lithiation, and intramolecular   cyclization to provide unstable lithiated benzoxazole moieties.   The subsequent in-line electrophilic quench results in the   formation of substituted benzoxazoles in high yield and quality.   Continuous flow technology allowed for accurate temperature   control and immediate in-line quench while minimizing the hold-up   time for the unstable lithiated intermediates thereby minimizing   associated byproduct formation.

      Address (URL): http://pubs.acs.org/doi/abs/10.1021%2Fol402706a