Sulfuric Acid → HCID 46781713, compound

HRID 578766Notes

Reaction equation

HRID 578766 reaction equation
[OH:1][S:2]([OH:5])(=[O:4])=[O:3].[CH3:6][N:7]1[C@@H:24]2[CH2:25][C:12]3=[CH:13][CH:14]=[C:15](O)[C:16]4[O:17][C@H:18]5[C:19]([CH2:21][CH2:22][C@@H:23]2[C@:10]5([C:11]=43)[CH2:9][CH2:8]1)=[O:20].C(#N)C.[OH-].[Na+]>CCO>[CH3:6][N:7]1[C@@H:24]2[CH2:25][C:12]3=[CH:13][CH:14]=[C:15]([O:3][S:2]([OH:5])(=[O:1])=[O:4])[C:16]4[O:17][C@H:18]5[C:19]([CH2:21][CH2:22][C@@H:23]2[C@:10]5([C:11]=43)[CH2:9][CH2:8]1)=[O:20]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 5284570Hydromorphone

Product 1

HCID 46781713HCID 46781713, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
81 °C

Procedure

Morphine base (30.0 g, wet, 75% wt, 78.85 mmol) was dried in a vacuum oven at 90° C. for 3 h. The dried solid was added to a reaction flask, along with water (30 mL) and EtOH (60 mL). The reaction mixture was stirred 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 catalyst (RuCl3.xH2O, 0.20 g). The reaction mixture was heated to reflux (80-82° C.) for 16 h. HPLC analysis indicated that 96.8% (area) hydromorphone was formed. The reaction mixture was cooled down overnight. Acetonitrile (30 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 11.6 g of hydromorphone sulfate as solids (purity>99% area).

Workup

  1. dry with materialMorphine base (30.0 g, wet, 75% wt, 78.85 mmol) was dried in a vacuum oven at 90° C. for 3 h
  2. additionThe dried solid was added to a reaction flask, along with water (30 mL) and EtOH (60 mL)
  3. customto form a suspension
  4. customThe reactor was flushed with nitrogen
  5. customthe reaction mixture was kept under nitrogen throughout the reaction
  6. temperatureThe reaction mixture was heated
  7. customwas formed
  8. temperatureThe reaction mixture was cooled down overnight
  9. temperaturethe mixture was heated
  10. temperatureat reflux for 1 h
  11. temperatureas cooled down to 15° C. for 1 h
  12. filtrationThe mixture was filtered
  13. washthe solid was washed with 95% EtOH (2×15 mL)
  14. customThe solid was dried under vacuum at 65° C. for 18 h

Sources & evidence

ORD record
ord-e975774f2623415994794ed0704b0a1b
Source dataset
uspto-grants-2015_05
Patent number
US09040705B2

Reaction notes

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