Implementation and scale-up of a semi-continuous transaminase-catalyzed reactive crystallization for the preparation of (S)-(3-methoxyphenyl)ethylamine

Abstract Unfavorable equilibrium positions are often a critical factor in the process development of biocatalytic reactions and usually require secondary solutions for efficient synthesis strategies. This explicitly applies to transaminase-catalyzed reactions, which can be used for the synthesis of enantiomerically pure amines. Overcoming the unfavorable equilibrium situation in these biocatalytic reactions, especially with a focus on efficient product isolation, has only been partly studied for preparative applications especially with higher concentration of a product amine. In this study, we present the process development of a transaminase-catalyzed reaction with the specific integration of an in situ-product crystallization, which allows downstream-processing via filtration in addition to the required equilibrium shift. This approach highlights a semi-continuous reaction concept with intermediate substrate addition and product removal in the form of a suspension-to-suspension reaction, supported by a light vacuum to remove the by-product acetone. Using the methodology up to 1.2 mol⋅L-−1 product amine could be obtained by an iterative process development. Thus, the presented method represents a high potential for the preparative application of amine-based biocatalytic reactions at larger scales.