Formic Acid → Oxycodone

HRID 1037631Notes

Reaction equation

HRID 1037631 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.C(O)=[O:25].OO>CC(O)C>[O:12]1[C@@H:13]2[C@@:5]34[CH2:4][CH2:3][N:2]([CH3:1])[C@@H:18]([C@:17]3([OH:25])[CH2:16][CH2:15][C:14]2=[O:20])[CH2:19][C:7]2=[C:6]4[C:11]1=[C:10]([O:22][CH3:23])[CH:9]=[CH:8]2

Participants

5

Reactant 3

HCID 284Formic AcidHCID 784Hydrogen PeroxideHCID 5324289Thebaine

Product 1

HCID 5284603Oxycodone

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
25 °C

Procedure

50 kg thebaine was added to a solution of formic acid (145 kg) maintained at a temperature below 15° C. the solution was heated to 25° C. and maintained at this temperature for 1.0 hr. the reaction mixture was cooled to 0-5° C. and 30% H2O2 aqueous solution (5.5 kg 100% H2O2) was added at 0-5° C. The reaction mixture was maintained at 20-25° C. for 3.0 hrs. After completion of the reaction, it was quenched in 560 lit DM water and treated with charcoal. To the filtrate 5% Pd/C (1.5 kg) was added and hydrogen gas purged at 20-25° C. The reaction mixture was maintained at 20-25° C. for 4-5 hrs. After reaction completion, the catalyst was filtered off and the pH of the filtrate was adjusted to 9-9.5 with aqueous ammonia. The product was extracted with methylene dichloride and subsequently concentrated to obtain a solid which was isolated with IPA. Yield: 41.7 kg

Workup

  1. temperaturemaintained at a temperature below 15° C. the solution
  2. temperaturemaintained at this temperature for 1.0 hr
  3. temperaturethe reaction mixture was cooled to 0-5° C.
  4. temperatureThe reaction mixture was maintained at 20-25° C. for 3.0 hrs
  5. customAfter completion of the reaction, it
  6. customwas quenched in 560
  7. additiontreated with charcoal
  8. additionTo the filtrate 5% Pd/C (1.5 kg) was added
  9. customhydrogen gas purged at 20-25° C
  10. temperatureThe reaction mixture was maintained at 20-25° C. for 4-5 hrs
  11. customAfter reaction completion
  12. filtrationthe catalyst was filtered off
  13. extractionThe product was extracted with methylene dichloride
  14. concentrationsubsequently concentrated
  15. customto obtain a solid which

Sources & evidence

ORD record
ord-8feae2b0fe0d4962974a3da7a1158dfc
Source dataset
uspto-grants-2013_10
Patent number
US08546572B2

Reaction notes

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