Decoration of the Aromatic Ring of Dihydrocodeinone (Hydrocodone) and 14-Hydroxydihydrocodeinone (Oxycodone)

Improved protocols for the preparation of 1-bromodihydrocodeinone (1-bromohydrocodone) and 1-bromo-14-hydroxydihydrocodeinone (1-bromooxycodone) and synthesis of the
corresponding 1-chloro and 1-iodo derivatives have been
achieved using the corresponding N-halosuccinimides in
acidic milieu. The corresponding 1-carboethoxy derivative
of 14-hydroxydihydrocodeinone (1-carboethoxyoxycodone)
has been prepared by Pd-catalyzed reaction with carbon
monoxide in ethanol. The ester was hydrolyzed to the
corresponding zwitterionic amino acid.