Acetic Acid → Oxymorphone

HRID 1513320Notes

Reaction equation

HRID 1513320 reaction equation
[C:1]([OH:4])(=O)[CH3:2].[CH3:5][N:6]1[C@@H]2[CH2:23][C:11]3[CH:12]=[CH:13][C:14]([OH:26])=[C:15]4[O:16][C@H:17]5[C:18]([O:24]C)=[CH:19][CH:20]=C2[C@:9]5([C:10]=34)[CH2:8][CH2:7]1.C(OO)(=O)C.OO>O>[CH3:5][N:6]1[C@@H:2]2[CH2:23][C:11]3=[CH:12][CH:13]=[C:14]([OH:26])[C:15]4[O:16][C@H:17]5[C:18]([CH2:19][CH2:20][C@:1]2([OH:4])[C@:9]5([C:10]=43)[CH2:8][CH2:7]1)=[O:24]

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 784Hydrogen PeroxideHCID 6585Peracetic Acid2×HCID 5462306Oripavine

Product 1

HCID 5284604Oxymorphone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
35 °C

Procedure

Glacial acetic acid, HOAc, (30 mL) and water (120 mL) were added to a 250 mL flask (pH=2.6, ˜150 mL). With the stirring mechanism on, oripavine (30.00 g, assayed to be 96% wt/wt, containing oripavine 97 mmol) was charged to the flask. Heat was released and the final solution reached 25° C. from 20° C., pH=3.66. The reaction mixture was cooled to 5˜10° C., and, CH3CO3H (23.4 g, containing 33% wt/wt peroxy acetic acid and 5.34% H2O2, 97 mmol peracetic acid) was added over 10 minutes. The reaction mixture was stirred for another 30 minutes after cooling bath was removed and the final temperature reached 15° C. H2C2O4 (1.5 g) was added to the reaction mixture, and the solution was heated to 35° C. over a 30 minute period and maintained at 35° C. for 1 hour. The reaction mixture was transferred to a pressure bearing flask (350 mL) for the reduction reaction. The flask for the oxidation was washed with the 2% HOAc (v/v; 2×7.5 mL). The washes were transferred to the reduction flask. 1.0 g of 10% Pd/C was added and the flask was pump/purged first with nitrogen and then with hydrogen each 4 times. The flask was cycled under vacuum and hydrogen 4 times. The reaction mixture was stirred under hydrogen (60 PSI) at 85° C. to 90° C. (90° C. oil bath) for 4.5 hours. The reaction mixture was cooled down to 35° C. and filtered. The recovered solid was washed with a solution of 2% HOAc/H2O (v/v, 3×15 mL). Yield of oxymorphone formed in the solution was calculated by HPLC analysis: 95%.

Workup

  1. temperatureHeat
  2. customreached 25° C. from 20° C.
  3. temperatureThe reaction mixture was cooled to 5˜10° C.
  4. additionwas added over 10 minutes
  5. temperatureafter cooling bath
  6. customwas removed
  7. customreached 15° C
  8. additionH2C2O4 (1.5 g) was added to the reaction mixture
  9. temperaturemaintained at 35° C. for 1 hour
  10. customThe reaction mixture was transferred to a pressure bearing flask
  11. custom(350 mL) for the reduction reaction
  12. washThe flask for the oxidation was washed with the 2% HOAc (v/v; 2×7.5 mL)
  13. addition1.0 g of 10% Pd/C was added
  14. customthe flask was pump/purged first with nitrogen
  15. stirringThe reaction mixture was stirred under hydrogen (60 PSI) at 85° C. to 90° C. (90° C. oil bath) for 4.5 hours
  16. temperatureThe reaction mixture was cooled down to 35° C.
  17. filtrationfiltered
  18. washThe recovered solid was washed with a solution of 2% HOAc/H2O (v/v, 3×15 mL)

Sources & evidence

ORD record
ord-76767fbb8070421eb0707633605c1ab5
Source dataset
uspto-grants-2012_07
Patent number
US08217175B2

Reaction notes

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