Kinetic investigation of the asymmetric hydrogenation of benzylphenylephrone in continuous flow: enabling R&D with flow chemistryand microfluidics

In the pharmaceutical industry, efficient, fast, and cost-effective API manufacturing processes are crucial for maintaining competitiveness. However, traditional production methods are often dominated by multi-purpose batch processes and empirical development approaches. This study presents the desi...

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Bibliographic Details
Main Authors: Moll, Maurice (Author) , Wängler, Björn (Author) , Wängler, Carmen (Author) , Röder, Thorsten (Author)
Format: Article (Journal)
Language:English
Published: 2025-06-25
In: Chimia
Year: 2025, Volume: 79, Issue: 6, Pages: 441-448
ISSN:2673-2424
DOI:10.2533/chimia.2025.441
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.2533/chimia.2025.441
Verlag, kostenfrei, Volltext: https://www.chimia.ch/chimia/article/view/2025_441
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Author Notes:Maurice Moll, Björn Wängler, Carmen Wängler, Thorsten Röder
Description
Summary:In the pharmaceutical industry, efficient, fast, and cost-effective API manufacturing processes are crucial for maintaining competitiveness. However, traditional production methods are often dominated by multi-purpose batch processes and empirical development approaches. This study presents the design and development of a fully automated, mL-scale continuous flow process for the asymmetric hydrogenation of benzylphenylephrone to (R)-benzylphenylephrine (BPE). The process employs a rhodium-based homogeneous catalyst under high pressure (up to 65 bar), achieving conversions of >96%, yields of up to 95% and high enantiomeric excess (ee) of up to 91%, with residence times of less than five minutes and a molar substrate to catalyst ratio (S/C) of 750. Kinetic investigations were conducted in a continuous flow microreactor, resulting in the development of a kinetic model that closely matches experimental data.
Item Description:Gesehen am 02.10.2025
Physical Description:Online Resource
ISSN:2673-2424
DOI:10.2533/chimia.2025.441