Hydrogen Peroxide → Oxycodone

HRID 1410417Notes

Reaction equation

HRID 1410417 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.OO.CC([OH:29])C>C(O)=O.[Pd]>[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:29])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:20]

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 3776IsopropanolHCID 5324289Thebaine2×

Product 1

HCID 5284603Oxycodone

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 284Formic AcidSolvent2×

Procedure

Thebaine (67 g, 0.215 mol) was dissolved in formic acid (98-100%, 120 g) and hydrogen peroxide (30% in water, 24.5 g, 0.216 mol) added at 0° C. The mixture was pumped continuously at 2 ml/min through a 30 ml continuous flow reactor at 80° C. (15 min residence time). An analytical control after the continuous reactor showed less than 1% Thebaine remaining. The continuous stream was added directly to the hydrogenation autoclave that was precharged with 2-propanol (204 g), formic acid (98-100%, 64 g) and 5% Pd/C (7.6 g) and held at 100° C. under H2 (40 bar). The hydrogenation was stirred for 16 h. After the hydrogenation, the catalyst was filtered off and the crude mixture was either basified with NaOH to obtain the low impurity Oxycodone base, or treated with HCl in 2-Propanol to give the Oxycodone HCl. The yields were 82% for the base and 78% for the HCl salt. The 14-Hydroxycodeinone content of the base was 49 ppm and of the HCl salt 29 ppm.

Workup

  1. customThe mixture was pumped continuously at 2 ml/min through a 30 ml continuous flow reactor at 80° C.
  2. custom(15 min residence time)
  3. additionThe continuous stream was added directly to the hydrogenation autoclave that
  4. customheld at 100° C. under H2 (40 bar)
  5. filtrationAfter the hydrogenation, the catalyst was filtered off

Sources & evidence

ORD record
ord-a458de005fef4dd094cc0833ec1401e9
Source dataset
uspto-grants-2014_12
Patent number
US08921557B2

Reaction notes

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