Hydrogen Peroxide → Oxycodone

HRID 860768

Reaction equation

HRID 860768 reaction equation
[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20]C)=[CH:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.[OH2:24].OO>C(O)=O>[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:15][CH2:16][C@:17]2([OH:24])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:20]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 962WaterHCID 5324289Thebaine

Product 1

HCID 5284603OxycodoneYield 87.7%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

Thebaine (15.94 g) was added to a 250 ml flask. Water (18 ml) was added and the mixture was stirred at room temperature. Formic acid (42 ml) was added over 3 minutes and then the mixture was cooled in an ice bath. Hydrogen peroxide (30%, 6.7 g) was added and the mixture was stirred for 1 hour. The mixture was removed from the ice bath, allowed to warm to room temperature and then heated to 48° C. for 2 hours. The mixture was transferred to a hydrogenation bottle. A 5 wt % palladium on carbon catalyst (2 g) was added and hydrogen was passed through the mixture at approximately 20 psi for 15 hours. The catalyst was removed by passing the mixture through a pad of celite and rinsing the filtered solid with water/formic acid (3:1, 8 ml). The mixture was cooled in an ice bath and 25% sodium hydroxide (109 ml) was added dropwise over 50 minutes to increase the pH to 9–10. The mixture was stirred for 1 hour and 15 minutes and the solid product was filtered, rinsed with cold water and dried under vacuum pump for 3 hours. The product was oxycodone base (14.152 g, 87.7% yield) and contained 178 ppm of the α,β-unsaturated ketone impurity, 14-hydroxycodeinone.

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. stirringthe mixture was stirred for 1 hour
  3. customThe mixture was removed from the ice bath
  4. temperatureto warm to room temperature
  5. temperatureheated to 48° C. for 2 hours
  6. additionA 5 wt % palladium on carbon catalyst (2 g) was added
  7. customThe catalyst was removed
  8. washrinsing the filtered solid with water/formic acid (3:1, 8 ml)
  9. temperatureThe mixture was cooled in an ice bath
  10. addition25% sodium hydroxide (109 ml) was added dropwise over 50 minutes
  11. temperatureto increase the pH to 9–10
  12. stirringThe mixture was stirred for 1 hour and 15 minutes
  13. filtrationthe solid product was filtered
  14. washrinsed with cold water
  15. customdried under vacuum pump for 3 hours

Sources & evidence

ORD record
ord-6e5e2861315b413eae23417179fe5b4f
Source dataset
uspto-grants-2006_12
Patent number
US07153966B2

Linked notes

Loading…