Sulfuric Acid → HCID 46781713, compound

HRID 578765Notes

Reaction equation

HRID 578765 reaction equation
[CH:1]1[C:17]2[CH2:16][C@H:15]3[N:18]([CH2:20][CH2:21][C@@:7]45[C@H:14]3[CH:13]=[CH:12][C@H:10]([OH:11])[C@@H:8]4[O:9][C:5]([C:6]=25)=[C:3]([OH:4])[CH:2]=1)[CH3:19].[OH:22][S:23](O)(=[O:25])=[O:24].CN1[C@@H]2CC3=CC=C(O)C4O[C@H]5C(CC[C@@H]2[C@]5(C=43)CC1)=O.[OH-].[Na+]>CCO.CS(C)=O.O>[CH3:19][N:18]1[C@@H:15]2[CH2:16][C:17]3=[CH:1][CH:2]=[C:3]([O:4][S:23]([OH:25])(=[O:24])=[O:22])[C:5]4[O:9][C@H:8]5[C:10]([CH2:12][CH2:13][C@@H:14]2[C@:7]5([C:6]=43)[CH2:21][CH2:20]1)=[O:11]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 5284570HydromorphoneHCID 5288826Morphine

Product 1

HCID 46781713HCID 46781713, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
81 °C

Procedure

A reaction flask was charged with morphine base (30.0 g, wet, 75% wt, 78.85 mmol), water (23 mL), and EtOH (60 mL). The reaction mixture was agitated to form a suspension. The reactor was flushed with nitrogen and the reaction mixture was kept under nitrogen throughout the reaction. The reaction flask was charged with H2SO4 (98%, 7.73 g, 78.85 mmol) and the catalysts (RuCl3.xH2O, 0.20 g). The reaction mixture was heated to reflux (80-82° C.) for 24 h. HPLC analysis indicated that 93% (area) hydromorphone was formed. The reaction mixture was cooled down overnight. DMSO (1.0 mL) was added to the reaction mixture and the mixture was heated at reflux for 1 h. The pH of the reaction mixture was adjusted the pH to 1.6 with 50% NaOH. EtOH (90 mL) was added to the mixture, which as cooled down to 15° C. for 1 h. The mixture was filtered, and the solid was washed with 95% EtOH (2×15 mL). The solid was dried under vacuum at 65° C. for 18 h to give 11.8 g of hydromorphone sulfate as solids (purity>99% area).

Workup

  1. customto form a suspension
  2. customThe reactor was flushed with nitrogen
  3. customthe reaction mixture was kept under nitrogen throughout the reaction
  4. temperatureThe reaction mixture was heated
  5. customwas formed
  6. temperatureThe reaction mixture was cooled down overnight
  7. temperaturethe mixture was heated
  8. temperatureat reflux for 1 h
  9. temperatureas cooled down to 15° C. for 1 h
  10. filtrationThe mixture was filtered
  11. washthe solid was washed with 95% EtOH (2×15 mL)
  12. customThe solid was dried under vacuum at 65° C. for 18 h

Sources & evidence

ORD record
ord-caf1435f883b48f288efb9cee34d2e1a
Source dataset
uspto-grants-2015_05
Patent number
US09040705B2

Reaction notes

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