Continuous flow Buchwald–Hartwig amination of a pharmaceutical intermediate†
Polina Yaseneva a, Paul Hodgson a, Jacek Zakrzewski a, Sebastian Falß b, Rebecca E. Meadows c, Alexei A. Lapkin * a
- a Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB2 3RA, UK. E-mail: email@example.com Fax: +44 (0)1223 334796
- b INVITE GmbH, Chempark Leverkusen, 51373 Leverkusen, Germany
- c Pharmaceutical Development, AstraZeneca, Silk Road Business Park, Macclesfield SK10 2NA, UKRead the publication that featured this abstract
A flow process for direct amination of a pharmaceutically relevant substrate using a Pd-NHC based catalyst was demonstrated in a lab-scale mini-plant and in a pilot-scale plant. The lab-scale mini-plant was used to determine catalyst stability under recycling conditions. Results in the mini-plant have shown the maximum space–time yield between the three types of reactor systems: a batch reactor, a mini-plant and a pilot plant. A comprehensive life-cycle assessment study of the synthesis of organometallic catalysts and their impact on the overall LCA of flow vs. batch syntheses was developed. Combined with a simplified economic analysis, the LCA study confirmed the benefits of switching to flow.
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