Preparation of 14-hydroxycodeinone sulfate

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 preparation of isolated 14-hydroxycodeinone hemisulfate dihydrate comprising
exposing thebaine to hydrogen peroxide or peroxyacid, and another organic acid, in the presence of sodium hydrogen sulfate, sodium sulfate, potassium sulfate, and/or potassium hydrogen sulfate in an aqueous reaction mixture; and isolating a precipitate of 14-hydroxycodeinone sulfate or a hydrate thereof from the reaction mixture.