Hydrogen Bromide → Codeine

HRID 1390816Notes

Reaction equation

HRID 1390816 reaction equation
[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20]C)=[CH:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.Br>C(O)(=O)C.CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O>[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C@@H:14]([OH:20])[CH:15]=[CH:16][C@@H:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 260Hydrogen BromideHCID 5324289Thebaine

Product 1

HCID 5284371CodeineYield 64.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterSolvent

Conditions

Temperature
20 °C

Procedure

A solution of thebaine (6.22 g) in glacial acetic acid (20 ml) was stirred at 15° C. and treated dropwise over 5 minutes with a 45% w/v solution of hydrogen bromide in glacial acetic adid (12.6 ml, 3.5 equivalents). TLC examination of a sample withdrawn 15 minutes after completion of the addition showed that the reaction was complete. The reaction mixture was then added slowly to a stirred slurry of sodium carbonate (62.5 g) in water (150 ml) keeping the temperature below 5° C. Methanol (250 ml) and water (100 ml) were added and the crude codeinone was reduced by portionwise addition of sodium borohydride (0.76 g) with stirring at 20° C. A sample was taken after 16 hours and the reduction was found to be complete (TLC). The reaction mixture was then filtered to remove inorganic solids and the filtrate was concentrated under reduced pressure until most of the methanol had been removed. The residual solid in the filter was washed with chloroform (100 ml) and the chloroform wash was used in two equal portions to extract the above aqueous concentrate. The chloroform extract was washed with water (25 ml), dried over sodium sulphate and the solvent removed under reduced pressure to give the title compound (3.88 g) identical by TLC and GLC with an authentic sample.

Workup

  1. customTLC examination of a sample withdrawn 15 minutes
  2. additionafter completion of the addition
  3. additionThe reaction mixture was then added slowly to a stirred slurry of sodium carbonate (62.5 g) in water (150 ml)
  4. customthe temperature below 5° C
  5. additionMethanol (250 ml) and water (100 ml) were added
  6. additionthe crude codeinone was reduced by portionwise addition of sodium borohydride (0.76 g)
  7. filtrationThe reaction mixture was then filtered
  8. customto remove inorganic solids
  9. concentrationthe filtrate was concentrated under reduced pressure until most of the methanol
  10. customhad been removed
  11. washThe residual solid in the filter was washed with chloroform (100 ml)
  12. washthe chloroform wash
  13. extractionto extract the above aqueous concentrate
  14. extractionThe chloroform extract
  15. washwas washed with water (25 ml)
  16. dry with materialdried over sodium sulphate
  17. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-bc1651d064574a31b7d664c45077dc8e
Source dataset
uspto-grants-1979_02
Patent number
US04140687

Reaction notes

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