Potassium Iodide → 6-Ketonalbuphine

HRID 39326

Reaction equation

HRID 39326 reaction equation
[CH3:1][N:2]1[C@@H:12]2[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([OH:20])=[C:16]4[O:21][C@H:6]5[C:7]([CH:9]=[CH:10][C@:11]2([OH:22])[C@:5]5([C:15]=34)[CH2:4][CH2:3]1)=[O:8].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].BrC[CH:33]1[CH2:36][CH2:35][CH2:34]1>CC(N(C)C)=O>[CH2:33]1[CH2:36][CH:35]([CH2:1][N:2]2[C@@H:12]3[CH2:13][C:14]4[CH:19]=[CH:18][C:17]([OH:20])=[C:16]5[O:21][C@H:6]6[C:7]([CH2:9][CH2:10][C@:11]3([OH:22])[C@:5]6([C:15]=45)[CH2:4][CH2:3]2)=[O:8])[CH2:34]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 2734658(Bromomethyl)cyclobutane2×HCID 1528625314-Hydroxymorphine-6-one2×

Product 1

HCID 444650036-KetonalbuphineYield 73.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Noroxymorphone (1.59 g, 5.5 mmol), potassium carbonate (0.61 g, 6.1 mmol), potassium iodide (0.46 g, 2.8 mmol), and dimethyl acetamide (10 mL) were added into a round bottom flask. Bromomethylcyclobutane (0.82 g, 5.5 mmol, 0.62 mL) was added. The reaction was stirred for 7 days at room temperature. At that time, bromomethylcyclobutane (0.82 g, 5.5 mmol, 0.62 mL) was added. The reaction was stirred for an additional 7 days. HPLC analysis indicated that the noroxymorphone was consumed. Distilled water (50 mL) was added and stirred at room temperature for 6 hours. An off-white precipitate formed, which was removed by filtration. The solid was washed with distilled water (25 mL), then slurried for 24 hours in acetonitrile (25 mL). Filtration, washing the solid with acetonitrile (10 mL), and drying at room temperature under vacuum for 24 hours yielded N-(cyclobutylmethyl)-noroxymorphone (1.43 g, 73% yield) as a tan solid.

Workup

  1. stirringThe reaction was stirred for an additional 7 days
  2. customwas consumed
  3. additionDistilled water (50 mL) was added
  4. stirringstirred at room temperature for 6 hours
  5. customAn off-white precipitate formed
  6. customwhich was removed by filtration
  7. washThe solid was washed with distilled water (25 mL)
  8. waitslurried for 24 hours in acetonitrile (25 mL)
  9. filtrationFiltration
  10. washwashing the solid with acetonitrile (10 mL)
  11. customdrying at room temperature under vacuum for 24 hours

Sources & evidence

ORD record
ord-51eb604ae3e04854819ac25796e786bd
Source dataset
uspto-grants-2013_09
Patent number
US08524904B2

Linked notes

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