Continuous Preparative Application of Amine Transaminase‐Catalyzed Reactions with Integrated Crystallization

Transaminases are valuable catalysts in the synthesis of chiral amines. However, secondary techniques are typically required to shift the reaction equilibrium to the product side. This study focuses on the in situ product crystallization, specifically at preparative synthetic scale as a non‐synthetic tool for a selection of aromatic and aliphatic substrates using the transaminase from Silicibacter pomeroyi. Herein the technique is implemented in a simplified manner to facilitate in situ product removal and downstream‐processing in a combined crystallization step. After a series of optimizations, product concentrations of >0.9 mol/L and >99 % e.e. (S) were obtained implementing a repetitive batch reaction approach using a universal carboxylate as anion. In situ product crystallization (ISPC) was used to semicontinuously remove chiral amines from amine transaminase catalyzed reactions. The use of a constant mild vacuum facilitated the synthesis of six compounds in this way in a preparative fashion at gram scale with yields of up to 80 %. The process included intermittent removal steps of the product salt and the replenishment of substrates every 24 h