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 anomer 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.