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

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 SN2' 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.