Sustainable Synthesis of Noroxymorphone via a Key Electrochemical N-Demethylation Step

Noroxymorphone is a pivotal intermediate in the synthesis of important opioid antagonists such as naloxone and naltrexone. The preparation noroxymorphone from thebaine, naturally occurring opioate isolated poppy extract, multistep sequence which oxycodone first generated then N- O-demethylated. Both demethylations are problematic safety sustainability viewpoint, they involve harmful reagents alkyl chloroformates or boron tribromide. Herein, we present green, safe, efficient process for O-demethylation oxycodone. method based on anodic oxidative intramolecular cyclization N-methyl tertiary amine with 14-hydroxyl group morphinan, followed by hydrolysis hydrobromic acid, releases carbon both heteroatoms. electrolysis has been transferred to scalable flow cell, significantly improving reaction throughput increasing space-time yield over 300-fold respect batch. new methodology assessed means green metrics qualitative indicators. assessment demonstrated that far superior conventional chloroformate process.