Sulfuric Acid → HCID 71468009, compound

HRID 578767Notes

Reaction equation

HRID 578767 reaction equation
[CH3:1][N:2]1[C@@H:7]2[CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]4[O:17][C@H:18]5[C@@H:19]([OH:22])[CH:20]=[CH:21][C@@H:6]2[C@:5]5([C:10]=34)[CH2:4][CH2:3]1.[OH:23][S:24]([OH:27])(=[O:26])=[O:25].CN1[C@@H]2CC3C=CC(OC)=C4O[C@H]5C(CC[C@@H]2[C@]5(C=34)CC1)=O.[OH-].[Na+]>CCO.C(#N)C.O>[CH3:1][N:2]1[C@@H:7]2[CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]4[O:17][C@H:18]5[C:19]([CH2:20][CH2:21][C@@H:6]2[C@:5]5([C:10]=34)[CH2:4][CH2:3]1)=[O:22].[S:24]([O-:27])([O-:26])(=[O:25])=[O:23]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 5284371CodeineHCID 5284569Hydrocodone

Product 1

HCID 71468009HCID 71468009, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
81 °C

Procedure

A reaction flask was charged with codeine base (10.0 g, 33.4 mmol), water (10 mL), and EtOH (20 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%, 1.8 mL, 33.4 mmol) and the catalyst (RuCl3.xH2O, 0.20 g). The reaction mixture was heated to reflux (80-82° C.) for 24 h. HPLC analysis indicated that 92% (area) hydrocodone was formed. The reaction mixture was cooled down overnight. Acetonitrile (30 mL) was added to the reaction mixture and the mixture was heated for 1 h. The pH of the reaction mixture was adjusted the pH to 2.5 with 50% NaOH. EtOH (90 mL) was added to the mixture, which as cooled down to 0-5° 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 8.32 g of hydrocodone 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 for 1 h
  8. temperatureas cooled down to 0-5° C. for 1 h
  9. filtrationThe mixture was filtered
  10. washthe solid was washed with 95% EtOH (2×15 mL)
  11. customThe solid was dried under vacuum at 65° C. for 18 h

Sources & evidence

ORD record
ord-1b3b59bf339649f48102ad663824ce0c
Source dataset
uspto-grants-2015_05
Patent number
US09040705B2

Reaction notes

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