title: A multistep flow process for the synthesis of highly functionalized benzoxazoles.
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.
authors.affiliation: Novartis Pharma AG , Fabrikstrasse 14, 4002 Basel, Switzerland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Sedelmeier
authors.forename: Fabio
authors.initials: F
authors.lastname: Lima
authors.forename: Alain
authors.initials: A
authors.lastname: Litzler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Martin
authors.forename: Francesco
authors.initials: F
authors.lastname: Venturoni
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000814:Aniline Compounds; D001583:Benzoxazoles