A multistep flow process for the synthesis of highly functionalized benzoxazoles
Jörg Sedelmeier1, Fabio Lima, Alain Litzler
1Novartis Pharma AG , Fabrikstrasse 14, 4002 Basel, Switzerland.
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.
Related Concept Videos
Benzene to Phenol via Cumene: Hock Process
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Electrophilic Aromatic Substitution: Sulfonation of Benzene
Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation
Electrophilic Aromatic Substitution: Friedel–Crafts Alkylation of Benzene
Electrophilic Aromatic Substitution: Friedel–Crafts Acylation of Benzene

![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
