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Synthesis of Mepivacaine and Its Analogues by a Continuous‐Flow Tandem Hydrogenation/Reductive Amination Strategy
Author(s) -
Suveges Nícolas S.,
de Souza Rodrigo O. M. A.,
Gutmann Bernhard,
Kappe C. Oliver
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700824
Subject(s) - reductive amination , chemistry , amide , amination , mepivacaine , combinatorial chemistry , aldehyde , flow chemistry , organic chemistry , catalysis , medicine , surgery , bupivacaine
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.