Hydrochloric Acid → Oxycodone Hydrochloride

HRID 860775Notes

Reaction equation

HRID 860775 reaction equation
[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].[ClH:24].[H][H]>[Pd].O.C(O)C>[CH3:1][N:2]1[C@@H:19]2[CH2:20][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:16][CH2:17][C@:18]2([OH:21])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:15].[ClH:24]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 5284603OxycodoneHCID 178418361HCID 178418361, compound

Product 1

HCID 5462350Oxycodone HydrochlorideYield 79.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
75 °C

Procedure

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)).

Workup

  1. additionwas added
  2. temperatureslowly cooled to room temperature
  3. stirringstirred overnight
  4. temperatureThe mixture was heated to 40° C.
  5. temperatureThe mixture was warmed to 56° C.
  6. washThe bottle and filtrate were rinsed with a hot solution of 1 ml water and 5 ml ethanol
  7. temperatureThe filtrate was slowly cooled to room temperature
  8. waitplaced in an ice bath for 30 minutes
  9. filtrationThe solid product was filtered
  10. washrinsed with cold ethanol
  11. customdried overnight under a vacuum pump

Sources & evidence

ORD record
ord-ec0d4f99489846a9a9e493ea8460aae4
Source dataset
uspto-grants-2006_12
Patent number
US07153966B2

Reaction notes

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