Studying the Morita-Baylis-Hillman Reaction in Continuous Flow Using Packed Bed Reactors

Conditions for the Morita-Baylis-Hillman reaction were developed under continuous flow using a packed bed reactor carrying 4-(dimethylamino)pyridine immobilized on silica. High reaction rates were obtained, as the packed bed reactor mimics super-stoichiometric catalyst loadings for the passing reaction mixture. Catalyst deactivation was circumvented by avoiding acrylate esters as the reaction partners. The developed flow protocol provided all desired Morita-Baylis-Hillman products in yields attaining 95% with typical retention times between just 30 and 60 min. Precise control of the retention time proved imperative for one example, in which optimal yield was attained in just 10 min, while outpacing sideproduct formation. Finally, a scale-out study was performed proving high stability of the packed bed reactor setup and catalyst for more than 20 h of operation.