Phosphoric Acid → Oxycodone

Participants

Reaction Steps

A known amount of THF (26.7 g) is charged into a 0.5 L RBF, and 3.05 g of 14-hydroxycodeinone is added into it. With stirring 120 g of aqueous phosphoric acid (1M, 9.8%) is added. The mixture is stirred until the entire solid dissolved. While stirring 40% aqueous sodium hydroxide is added (12.5 g) dropwise over a 30-minute period until the pH of the solution reaches 6.20–6.30. An aqueous thiourea solution (0.001% w/w, 20.0 g) is then added to the reaction flask. This buffered solution is charged into a stainless hydrogenation vessel, followed by the addition of 0.150 g of 5% palladium on barium sulfate (dry basis). The vessel is sealed, pressurized to 15 psi with nitrogen, and then ventilated. This operation is repeated 3 times with nitrogen, and then with hydrogen. The reaction vessel is finally pressurized to 15 psi with hydrogen, and is stirred at this pressure until the reaction is completed (6 hours, residual 14-hydroxycodeinone<0.5 a/a % by HPLC). The hydrogenated solution is taken out from the stainless vessel. The catalyst is vacuum filtered off through a pad of Celite. The autoclave is rinsed with water (2×5 g) and the rinses are used to wash the catalyst cake on the filter. The filtrates are combined in a 0.5 L beaker with a magnetic stirrer. The solution is cooled in an ice-bath for 30 minutes and 15.5 g of ammonium hydroxide is added dropwise over a period of 30 minutes while cooling and brisk stirring continued. The addition of aqueous ammonia is mildly exothermic, so the rate of addition should be controlled such that the temperature does not exceed 30° C. A fine white precipitate formed during the basification process. The final pH of the suspension is 10–12. The precipitate is continuously cooled and stirred for 1 hour. It is then filtered, washed with water (3×10 g), and vacuum-dried for 3 h. A white solid of oxycodone (2.80 g, 91%) is obtained.

Provenance & Evidence