SYNTHESIS OF OXYCODONE HYDROCHLORIDE

摘要

Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.

主权项

1. A method for preparing oxycodone comprising
exposing thebaine to hydrogen peroxide or peroxyacid and another organic acid in the presence of a sulfate anion source selected from the group consisting of sodium hydrogen sulfate, sodium sulfate, potassium sulfate, potassium hydrogen sulfate and sulfuric acid in an aqueous reaction mixture to form 14-hydroxycodeinone sulfate; reducing the 14-hydroxycodeinone sulfate in the presence of a catalyst to form oxycodone base; and dissolving the oxycodone base in an aqueous organic acid to form an oxycodone organic acid salt.