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An Integrated Continuous‐Flow Synthesis of a Key Oxazolidine Intermediate to Noroxymorphone from Naturally Occurring Opioids
Author(s) -
Mata Alejandro,
Cantillo David,
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.201700811
Subject(s) - chemistry , oxazolidine , thebaine , continuous flow , flow chemistry , yield (engineering) , oxymorphone , hydroxylation , organic chemistry , catalysis , combinatorial chemistry , opioid , mechanics , medicine , biochemistry , physics , materials science , codeine , oxycodone , morphine , receptor , metallurgy , pharmacology , enzyme
A telescoped procedure for the direct preparation of an advanced intermediate towards noroxymorphone from the naturally occurring alkaloids oripavine and thebaine is presented. The reaction procedure involves an intensified continuous‐flow hydroxylation, followed by a continuous solvent switch and hydrogenation in a packed‐bed hydrogenator (H‐Cube). The obtained reaction mixture, containing oxymorphone as intermediate in excellent yield and purity, can be then directly converted into the desired noroxymorphone oxazolidine intermediate through palladium catalyzed N ‐methyl oxidation.