Three case studies will be described where continuous processing provides more efficient and greener synthetic routes to Active Pharmaceutical Ingredients.  In the first case, flow chemistry enabled the synthesis of an H3 antagonist.  Rapid mixing and temperature control in a plug flow reactor (PFR) minimized multiple additions and enolization during a rapid organometallic addition reaction under non-cryogenic conditions.  In the second case, aerobic oxidation of a heterocycle with an oxygen-nitrogen mixture promoted by activated carbon in a gas-liquid flow reactor (GLFR) gave a shorter route to tafamidis with less than half the number of unit operations and one tenth the E-factor relative to the original synthesis.  In the third case, the GLFR is applied to the flow hydrogenation of pharmaceutical intermediates with increased activity and selectivity.  Physical measurements including a fiber optic temperature probe allow characterizing the reactive zone within the catalyst bed showing the importance of the ratio of gas and liquid flows under operating conditions.<br/>

Flow chemistry for greener and more efficient API synthesis

2019 Spring National Meeting

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