(4R,4aS,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one → Oxycodone

HRID 567429Notes

Reaction equation

HRID 567429 reaction equation
[CH3:1][N:2]1[C@@H:12]2[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]4[O:22][CH:6]5[C:7]([CH:9]=[CH:10][C@:11]2([OH:23])[C@:5]5([C:15]=34)[CH2:4][CH2:3]1)=[O:8]>C(O)(=O)C>[CH3:1][N:2]1[C@@H:12]2[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]4[O:22][C@H:6]5[C:7]([CH2:9][CH2:10][C@:11]2([OH:23])[C@:5]5([C:15]=34)[CH2:4][CH2:3]1)=[O:8]

Participants

3

Reactant 1

HCID 5359420(4R,4aS,12bS)-4a-hydroxy-9-methoxy-3-methyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one2×

Product 1

HCID 5284603OxycodoneYield 70%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

14-Hydroxycodeinone (4.98 g) and acetic acid (155 g) were added to a Parr shaker equipped with hydrogen inlet and outlet connectors. The mixture was shaken for about 5 minutes to completely dissolve the 14-hydroxycodeinone at ambient temperature. The system was then evacuated and the Parr shaker was filled with nitrogen. In one portion, under the nitrogen atmosphere, 10% Pd/C (50% water wet, 4.0 g) was added. The system was then evacuated, and was filled with hydrogen gas to a pressure of about 38 psi. The hydrogen inlet from the supply tank was then closed and the mixture was shaken at an initial pressure of 38 psi for about 3 hours (at ambient temperature). After 3 hours of shaking, the system was evacuated and filled with nitrogen. The contents were filtered over a hyflo-supercel filtering pad (3 g, wetted with water). The Parr bottle and wet cake were then rinsed with acetic acid (2×21 g). The filtrate was concentrated in vacuo to dryness at temperature NMT 50° C. The residue was then dissolved with de-ionized water (50 g), and the pH adjusted to about 11.0 to 12.0 using 20% aqueous KOH solution and concentrated ammonium hydroxide (4 g). The mixture was then extracted with ethyl acetate (4×135 g), and the combined organic layers concentrated in vacuo to dryness. A yield of 3.51 to 4.26 g of crude oxycodone with HPLC purity of over 85A% (70.0 to 85.0% yield) was obtained.

Workup

  1. customequipped with hydrogen inlet and outlet connectors
  2. customThe system was then evacuated
  3. additionthe Parr shaker was filled with nitrogen
  4. additionIn one portion, under the nitrogen atmosphere, 10% Pd/C (50% water wet, 4.0 g) was added
  5. customThe system was then evacuated
  6. additionwas filled with hydrogen gas to a pressure of about 38 psi
  7. customThe hydrogen inlet from the supply tank was then closed
  8. stirringthe mixture was shaken at an initial pressure of 38 psi for about 3 hours (at ambient temperature)
  9. stirringAfter 3 hours of shaking
  10. customthe system was evacuated
  11. additionfilled with nitrogen
  12. filtrationThe contents were filtered over a hyflo-supercel
  13. filtrationfiltering pad (3 g, wetted with water)
  14. washThe Parr bottle and wet cake were then rinsed with acetic acid (2×21 g)
  15. concentrationThe filtrate was concentrated in vacuo to dryness at temperature NMT 50° C
  16. dissolutionThe residue was then dissolved with de-ionized water (50 g)
  17. extractionThe mixture was then extracted with ethyl acetate (4×135 g)
  18. concentrationthe combined organic layers concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-56f288ca022b47c38be1f81e028332e4
Source dataset
uspto-grants-2001_01
Patent number
US06177567B1

Reaction notes

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