Acetone → Oxycodone

HRID 1410419Notes

Reaction equation

HRID 1410419 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(C)=[O:28].Cl>C(O)=O.CO>[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:28])[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:20]

Participants

7

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 5324289Thebaine2×

Product 1

HCID 5284603OxycodoneYield 80%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolvent2×HCID 887MethanolSolvent

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 acetone, containing 32% HCl, whereupon the 14-Hydroxycodeinone HCl was precipitated and isolated in 80% yield. The 14-Hydroxycodeinone HCl was then dissolved in MeOH and HCOOH (4:1 w/w) and hydrogenated at 80° C. under 15 bar H2 pressure. The hydrogenation was stirred for 20 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 14-Hydroxycodeinone content of the base was 48 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. customwhereupon the 14-Hydroxycodeinone HCl was precipitated
  4. customisolated in 80% yield
  5. customhydrogenated at 80° C.
  6. filtrationAfter the hydrogenation, the catalyst was filtered off

Sources & evidence

ORD record
ord-396e4a21c76040599b1bbcf17c1e6c9c
Source dataset
uspto-grants-2014_12
Patent number
US08921557B2

Reaction notes

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