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.