- Synthesis of Mepivacaine and Its Analogues by a Continuous-Flow Tandem Hydrogenation/Reductive Amination Strategy
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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 ProTM) 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.
- Suveges, Nícolas S.,de Souza, Rodrigo O. M. A.,Gutmann, Bernhard,Kappe, C. Oliver
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p. 6511 - 6517
(2017/12/02)
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- Radical fixation of functionalized carbon resources: α-sp 3C - H carbamoylation of tertiary amines with aryl isocyanates
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A new carbamoylation of tertiary amines is reported. This rare C - H transformation features the direct generation of α-aminoalkyl radicals from tertiary amines, followed by the addition of the resultant nucleophilic radicals to isocyanates, enabling unique access to N,N-dialkylated amino acid derivatives. The authors put forward a mechanistic proposal that is based on the isolation of borinamides produced by capturing nitrogen radical intermediates with Et3B. The present transformation provides a novel one-step process for producing mepivacaine, a clinically important local anesthetic, from readily available materials.
- Yoshimitsu, Takehiko,Matsuda, Kenichi,Nagaoka, Hiroto,Tsukamoto, Koji,Tanaka, Tetsuaki
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p. 5115 - 5118
(2008/03/28)
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- Local anaesthetic salts of chondroitinsulfate compounds
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Water-soluble local anaesthetic compounds having sustained effect are prepared by reacting a chondroitin derivative with a basic local anaesthetic compound.
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