Application 1009

Multistep synthesis or simultaneous extraction simplified in a rotating bed reactor

The synthesis of products, such as active pharmaceutical ingredients (APIs), often involves multiple steps using heterogeneous catalysts or adsorbents. Thus, the simultaneous use of multiple solid phases either during synthesis or downstream processing is frequently highly advantageous.

“With traditional multistep syntheses, intermediates are usually isolated prior to the next manipulation, resulting in long overall process times and the generation of unnecessary chemical waste.” - Pieber, B., Gilmore, K., Seeberger, P.H., Integrated Flow Processing — Challenges in Continuous Multistep Synthesis

The workup between the series of steps in a synthesis route can lead to solvent waste and a larger total footprint of the process. If the stability of an intermediate is poor, the need for simultaneous production of subsequent products is amplified. In a fixed bed reactor, multiple resins are most easily packed in layers, but that deployment does not provide a solution to challenges like:

Simultaneous catalysis and cofactor regeneration
Metal catalysis and simultaneous scavenging
In-situ product removal for higher conversion

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The rotating bed reactor can easily be used with multiple solids of different properties, simultaneously and without any negative effects. In this video, see how two dyes were simultaneously and selectively adsorbed onto two materials in this video, demonstrating the concept of a one-pot multi-step synthesis.

Materials that might be incompatible with each other in a stirred tank reactor or fixed bed are easily loaded in the RBR. Complimentary solid phases can be used, such as an immobilized metal catalyst and a scavenger resin, or a multi-enzyme setup. The result is synergistic effects and a simplified process, for instance:

One-pot synthesis possibility
Simultaneous production and purification
Increased yields
Reduced waste

Further reading:

Details

Conditions: Allura red (40 µM) and methylene blue (13 µM) in deionized water (about 160 mL) were adsorbed onto Amberlite IRA900 Cl (13 mL, 650-820 µm) and Amberlite XAD1600N (13 mL, 400±50 µm), respectively. Each adsorbent was filled into two of the four compartments in a SpinChem® S2 rotating bed reactor (RBR) operated at 800 rpm within a SpinChem® V2 flower-baffled reaction vessel. The total extraction time for one run was nine minutes and the video contains photos of the adsorbents before and after two repeated extractions.