Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut

Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut

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...

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Veröffentlicht in:Organic letters 2020-10, Vol.22 (20), p.8122-8126
Hauptverfasser: Ötvös, Sándor B, Llanes, Patricia, Pericàs, Miquel A, Kappe, C Oliver
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container_title Organic letters
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creator Ötvös, Sándor B
Llanes, Patricia
Pericàs, Miquel A
Kappe, C Oliver
description 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 -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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title Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut
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