Continuous Synthesis and Purification by Coupling a Multistep Flow Reaction with Centrifugal Partition Chromatography

Continuous‐flow multistep synthesis is combined with quasi‐continuous final‐product purification to produce pure products from crude reaction mixtures. In the nucleophilic aromatic substitution of 2,4‐difluoronitrobenzene with morpholine followed by a heterogeneous catalytic hydrogenation, the desired monosubstituted product can be continuously separated from the co‐ and by‐products in a purity of over 99 % by coupling a flow reactor sequence to a multiple dual‐mode (MDM) centrifugal partition chromatography (CPC) device. This purification technique has many advantages over HPLC, such as higher resolution and no need for column replacement or silica recycling, and it does not suffer from irreversible adsorption. Das gewünschte monosubstituierte Produkt der nukleophilen aromatischen Substitution von 2,4‐Difluornitrobenzol mit Morpholin und anschließenden heterogen‐katalytischen Hydrierung kann kontinuierlich von den Neben‐ und Koppelprodukten getrennt werden – und zwar in einer Reinheit von über 99 % –, indem ein Durchflussreaktor an einen multiplen dualen Zentrifugalverteilungschromatographen angeschlossen wird.