Reaction #82145

ord-0aa465a90faf45259833d00a44a98cf2

Reaction equation

CCOCC
ether
CC(=O)OC(C)=O
acetic anhydride
CN1CC[C@]23c4c5ccc(O)c4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5
morphine
→
CC(=O)C1(O)CC=C2C[C@@H]3[C@@H]4C=C[C@H](O)[C@@H]5OC1=C2[C@]45CCN3C
3-acetylmorphine
Yield 80.0%

Reactants

CCOCC
ether
CC(=O)OC(C)=O
acetic anhydride
CN1CC[C@]23c4c5ccc(O)c4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5
morphine
—
ice

Reagents

None

Solvents

O=C([O-])O.[Na+]
sodium bicarbonate

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.ADDITIONwas added
  2. 2
    Extractionthe solution was extracted with dichloromethane (200 ml)
  3. 3
    ExtractionThe organic extract
  4. 4
    Washwas washed with brine
  5. 5
    Dryingdried over Na2SO4
  6. 6
    Otherthe solvent removed in vacuo
  7. 7
    Otherto leave a sticky white residue

Procedure

To a stirred suspension of morphine (4 g, 14 mmol) in 10% aqueous sodium bicarbonate (377 ml) was added acetic anhydride (19 ml) over 8.5 minutes. 15 minutes after the addition, ice cold water (300 ml) was added and the solution was extracted with dichloromethane (200 ml). The organic extract was washed with brine, dried over Na2SO4, and the solvent removed in vacuo to leave a sticky white residue. Trituration with ether gave 3-acetylmorphine (3.68 g, 80%). The corresponding 3-pivalyl, 3-isobutyryl, 3-propionyl and other 3-acyl derivatives of morphine were also prepared.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05621087uspto-grants-1997_04