Synthesis of Mepivacaine and Its Analogues by a Continuous‐Flow Tandem Hydrogenation/Reductive Amination Strategy

Herein we report a convenient, fast, and high‐yielding method for the generation of the racemic amide anaesthetics mepivacaine, ropivacaine, and bupivacaine. Coupling of α‐picolinic acid and 2,6‐xylidine under sealed‐vessel microwave conditions generates the intermediate amide after a reaction time of only 5 min at 150 °C. Subsequent reaction in a continuous‐flow high‐pressure hydrogenator (H‐Cube Pro TM ) in the presence of the respective aldehyde directly converts the intermediate to the final amide anaesthetics in a continuous, integrated, multi‐step ring‐hydrogenation/reductive amination protocol. Merits and limitations of the protocol are discussed.