Sustainable synthesis of long-acting local anesthetics ropivacaine and levobupivacaine under batch and continuous flow via asymmetric hydrogenation

Abstract

Ropivacaine and levobupivacaine, long-acting local anesthetics, have been sustainably synthesized using both batch and continuous flow methods. The key reaction, iridium-catalyzed enantioselective hydrogenation of 2-alkoxycarbonyl pyridinium salts, proceeds with excellent yields and enantioselectivities, as well as mild reaction conditions under both batch and flow modes. This approach provides a direct and sustainable pathway to obtain both (R)- and (S)-enantiomers of valuable piperidine-2-carboxylates.