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Updated: Dec 6, 2025

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid
Published on: November 15, 2017
Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen,
Sándor B Ötvös1,2, Patricia Llanes3, Miquel A Pericàs3,4
1Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Abstract:
The two-step flow asymmetric synthesis of chiral γ-nitrobutyric acids as key intermediates of the GABA analogues baclofen, phenibut, and fluorophenibut is reported on a multigram scale. The telescoped process comprises an enantioselective Michael-type addition facilitated by a polystyrene-supported heterogeneous organocatalyst under neat conditions followed by in situ-generated performic acid-mediated aldehyde oxidation. Simple access to valuable optically active substances is provided with key advances in terms of productivity and sustainability compared to those of previous batch approaches.
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