The development of a continuous, high pressure, iridium catalyzed reductive amination is disclosed. The bulky, stoichiometric reducing agent sodium triacetoxyborohydride was replaced with a catalytic process based on minimizing waste and generating a greener set of reaction conditions. Reaction optimization including, choice of catalyst, solvent and reagent choices and reaction conditions in batch mode will be discussed. Additives were screened to maximize catalyst stability while avoiding long reaction times which resulted in epimerization of the aldehyde to generate the cis isomer of the desired product. An overall understanding of the reaction and catalyst system was gained utilizing flow NMR and in-line HPLC monitoring. The translation of these conditions into a continuous pipes in series reactor at several reaction scales along with the inherent safety provided by the continuous equipment set when compared to the same chemistry in batch mode will be highlighted. Finally, the overall robustness of the reaction will be described including proper startup of the continuous reaction and poisons that can hamper catalytic activity.

Development of a continuous, high-pressure reductive amination

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.