Kinetic Investigation of the Asymmetric Hydrogenation of Benzylphenylephrone in Continuous Flow

Abstract

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.

Keywords: Catalytic asymmetric hydrogenation; Continuous flow chemistry; Kinetic modelling; Process development.