Hydrochloric Acid → Oxycodone Hydrochloride

Participants

Reaction Conditions

Reaction Steps

3 g of oxycodone product from comparative example 2 was added to a 50 ml flask. Water (1.3 ml) and ethanol (5.58 ml) were added and the mixture was stirred. Concentrated hydrochloric acid (1.58 ml) was added. Further water was added so that in total 4.5 ml of water was added. The mixture was heated to 75° C. for 10 hours, slowly cooled to room temperature and stirred overnight. The mixture was heated to 40° C. and transferred to a hydrogenation bottle. 5 wt % palladium on carbon catalyst (0.3 g) was added to the mixture and hydrogen was passed through the mixture at between 11 and 12 psi for 6.5 hours. The mixture was warmed to 56° C. and passed through two layers of filter paper. The bottle and filtrate were rinsed with a hot solution of 1 ml water and 5 ml ethanol, and with 20 ml of hot ethanol. The filtrate was slowly cooled to room temperature and then placed in an ice bath for 30 minutes. The solid product was filtered, rinsed with cold ethanol and dried overnight under a vacuum pump. The product was oxycodone hydrochloride (2.663 g, 79.6% yield). A further 0.334 g of oxycodone hydrochloride was obtained by washing the filter cake and hydrogenation bottle with water and water/ethanol (1:1), giving a combined yield of 2.997 g and 89.5%. Both samples of oxycodone hydrochloride contained 0 ppm 14-hydroxycodeinone (measured by HPLC and MS-SIM (mass spectrometry with selected ion monitoring)).

Provenance & Evidence