DEVELOPMENT OF A METHOD FOR PRODUCING (-)-17-ALLYL-4,5Ά-EPOXY-3,14-DIHYDROXYMORPHINAN-6-ONE

Naloxone ((-)-17-allyl-4,5ά-epoxy-3,14-dihydroxymorphinan-6-one) is a pure opiate antagonist of a competitive type devoid of morphine-like activity and is widely used in clinical practice. The main raw material for the production of naloxone is thebaine, which is extracted from plant materials. This study presents a seven-step process for preparing naloxone with a yield of 35% (based on thebaine). Previously known methods of obtaining are characterized by the yield of the target product in terms of thebaine not higher than 20%. The greatest losses are recorded at the stage of obtaining oxycodone from thebaine and at the stage of O-demethylation of codeine. The use of formic acid in the hydrogenation process provides a more complete conversion of the intermediate product, and the use of boron tribromide in the environment of chloroalkanes at the stage of O-demethylation leads to the production of naloxone with a yield of more than 70%. A detailed study of the stages of obtaining oxycodone and noroxycodone allows to reduce the consumption of reagents and the time spent in the reactor, which is essential for reducing the cost of the final product. The proposed method is superior to those known in terms of productivity and economic efficiency and can be used for the development of industrial technology for the production of naloxone and its derivatives.