Acetic Acid → Oxymorphone

HRID 1513319Notes

Reaction equation

HRID 1513319 reaction equation
[CH3:1][C:2]([OH:4])=O.[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:1]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@:2]2([OH:4])[C@:9]5([C:10]=43)[CH2:8][CH2:7]1)=[O:24]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 6585Peracetic AcidHCID 5462306Oripavine

Product 1

HCID 5284604Oxymorphone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
35 °C

Procedure

HOAc (30 mL) and water (120 mL) were added to a 250 mL flask (pH=2.6, ˜150 mL). With the agitator on, oripavine (30.00 g, assayed to be 96% wt/wt, containing oripavine 97 mmol) was charged to the flask (final pH=3.66). Heat was released and the final solution reached 25° C. from 20° C., pH=3.66. The reaction mixture was cooled to 5° C. to 10° C., and, CH3CO3H (23.4 g, containing 33% wt/wt peroxyacetic acid and 5.34% H2O2 containing 97 mmol peracetic acid) was added over 10 minutes. Heat was released during the addition and the reaction temperature was maintained below 15° C. (primarily 10° C. to 15° C.) during the addition by ice water bath. The cooling bath was removed after the addition was completed. The temperature of the reaction mixture was 10° C. at this point. The reaction mixture was stirred for another 30 minutes after cooling bath was removed and the final temperature reached 15° C. Ascorbic acid (1.5 g) was added to the reaction mixture. The solution was heated to 35° C. over a 30 minute period and maintained at 35° C. for 1 hour afterwards. 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° C. to 10° C.
  4. additionwas added over 10 minutes
  5. temperatureHeat
  6. additionwas released during the addition
  7. temperaturethe reaction temperature was maintained below 15° C. (primarily 10° C. to 15° C.)
  8. additionduring the addition by ice water bath
  9. customThe cooling bath was removed
  10. additionafter the addition
  11. customwas 10° C. at this point
  12. temperatureafter cooling bath
  13. customwas removed
  14. customreached 15° C
  15. additionAscorbic acid (1.5 g) was added to the reaction mixture
  16. temperaturemaintained at 35° C. for 1 hour afterwards
  17. customThe reaction mixture was transferred to a pressure bearing flask
  18. custom(350 mL) for the reduction reaction
  19. washThe flask for the oxidation was washed with the 2% HOAc (v/v; 2×7.5 mL)
  20. addition1.0 g of 10% Pd/C was added
  21. customthe flask was pump/purged first with nitrogen
  22. stirringThe reaction mixture was stirred under hydrogen (60 PSI) at 85° C. to 90° C. (90° C. oil bath) for 4.5 hours
  23. temperatureThe reaction mixture was cooled down to 35° C.
  24. filtrationfiltered
  25. washThe recovered solid was washed with a solution of 2% HOAc/H2O (v/v, 3×15 mL)

Sources & evidence

ORD record
ord-c5fada81a6634e36b46b976c3734c9ea
Source dataset
uspto-grants-2012_07
Patent number
US08217175B2

Reaction notes

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