Process design methodology for organometallic chemistry in continuous flow systems |
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Authors: | Sarah M Hunter Flavien Susanne Robert Whitten Thoralf Hartwig Mark Schilling |
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Institution: | GlaxoSmithKline, GSK Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2, NY, UK |
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Abstract: | This publication summarises the methodology applied in the process design and scale up of fast, exothermic reactions using organometallic reagents for synthesis of intermediates in the production of Active Pharmaceutical Ingredient (API). Process understanding was developed by calculation of the kinetic parameters of the desired reactions and subsequent degradation of the reaction products along with calorimetric understanding. A reaction model, developed in silico, was used to specify process parameters to maximise yield and limit product degradation. The designed process operates with pseudo-adiabatic reaction conditions, from ambient temperatures with negligible impurity formation. |
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Keywords: | Flow chemistry Continuous process Grignard Organometallic |
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