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Organophotocatalytic N‐Demethylation of Oxycodone Using Molecular Oxygen
Author(s) -
Chen Yuesu,
Glotz Gabriel,
Cantillo David,
Kappe C. Oliver
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905505
Subject(s) - demethylation , oxycodone , reagent , chemistry , stoichiometry , yield (engineering) , nalbuphine , combinatorial chemistry , opioid , organic chemistry , materials science , biochemistry , gene expression , receptor , metallurgy , dna methylation , gene
N‐Demethylation of oxycodone is one of the key steps in the synthesis of important opioid antagonists like naloxone or analgesics like nalbuphine. The reaction is typically carried out using stoichiometric amounts of toxic and corrosive reagents. Herein, we present a green and scalable organophotocatalytic procedure that accomplishes the N‐demethylation step using molecular oxygen as the terminal oxidant and an organic dye (rose bengal) as an effective photocatalyst. Optimization of the reaction conditions under continuous flow conditions using visible‐light irradiation led to an efficient, reliable, and scalable process, producing noroxycodone hydrochloride in high isolated yield and purity after a simple workup.