A One-Step Synthesis of β-Bromocodide from Codeine.

Abstract

Opioid analgesics are the treatment of choice for chronic, severe pain. During the course of developing new derivatives of morphine and codeine, we observed an unanticipated S_N2' substitution reaction product during an attempted 3-O-demethylation of codeine using BBr₃. NMR spectroscopy and X-ray crystallographic data indicate that a significant product is β-bromocodide, a useful intermediate for the production of C-6-demethoxythebaine derivatives. Herein we report the first, single-step synthesis of β-bromocodide.