Continuous Flow Photochemical Benzylic Bromination of a Key Intermediate in the Synthesis of a 2‐Oxazolidinone

• Yuesu Chen^{a, b}
• Oscar de Frutos^c
• Carlos Mateos^c
• Juan A. Rincon^c
• David Cantillo^{*a, b}
• C. Oliver Kappe^{*a, b}

• ^a Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz (Austria)
• ^b Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz (Austria)
• ^c Centro de Investigacin Lilly S. A. Avda. de la Industria 30, 28108 Alcobendas-Madrid (Spain)

A continuous flow protocol for the benzylic photobromination of methyl N,N‐bis(tert‐butoxycarbonyl) phenylalaninate (3) is presented. This photochemical transformation generating brominated intermediate 4 is the critical step in synthesis of oxazolidinone 5, a key intermediate for the preparation of active pharmaceutical ingredients. The reaction was optimized in three continuous flow photoreactors: a self‐made reactor based on a T5 8 W black light lamp, as well as the commercially available VapourTec® UV‐150 and Corning® Advanced‐Flow™ reactors, both equipped with LED light sources. Under optimal conditions, concentrated solutions (95 g/L) of the starting material could be processed on multi‐gram scale, providing high conversion (96%) within 7 min at 30 °C, using 2 equivalents of N‐bromosuccinimide (NBS).

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