[en] A continuous flow procedure for the benzylic photobromination of methyl N,N-bis (tert-butoxycarbonyl) phenylalaninate is presented. This photochemical transformation generating the brominated intermediate is the critical step in the synthesis of the oxazolidinone methyl (4S,5R)-3-N-tert-Butoxycarbonyl-5-phenyl-1,3-oxazolidin-2-oxo-4-carboxylate, 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 a multi-gram scale, providing high conversion (96 %) within 7 min at 30 °C, using 2 equivalents of N-bromosuccinimide (NBS).
Disciplines :
Chemistry
Author, co-author :
Chen, Yuesu ; Université de Liège - ULiège > Molecular Systems (MolSys) ; Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Graz, Austria ; Institute of Chemistry, University of Graz, Graz, Austria
de Frutos, Oscar; Centro de Investigación Lilly S. A., Alcobendas-Madrid, Spain
Mateos, Carlos; Centro de Investigación Lilly S. A., Alcobendas-Madrid, Spain
Rincon, Juan A.; Centro de Investigación Lilly S. A., Alcobendas-Madrid, Spain
Cantillo, David; Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Graz, Austria ; Institute of Chemistry, University of Graz, Graz, Austria
Kappe, C. Oliver ; Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), Graz, Austria ; Institute of Chemistry, University of Graz, Graz, Austria
Language :
English
Title :
Continuous Flow Photochemical Benzylic Bromination of a Key Intermediate in the Synthesis of a 2-Oxazolidinone
Austrian Federal Ministry of Transport Innovation and Technology Austrian Federal Ministry of Science Research and Economy State of Styria
Funding text :
The CC FLOW Project (Austrian Research Promotion Agency FFG No. 862766) is funded through the Austrian COMET Program by the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT), the Austrian Federal Ministry of Science, Research and Economy (BMWFW), and by the State of Styria (Styrian Funding Agency SFG). The authors gratefully acknowledge Corning SAS for the provision of the Corning® Lab Photo Reactor.
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