Acetic Acid → Hydromorphone

HRID 748600Notes

Reaction equation

HRID 748600 reaction equation
[CH:1]1[C:17]2[CH2:16][C@H:15]3[N:18]([CH2:20][CH2:21][C@@:7]45[C@H:14]3[CH:13]=[CH:12][C@H:10]([OH:11])[C@@H:8]4[O:9][C:5]([C:6]=25)=[C:3]([OH:4])[CH:2]=1)[CH3:19].C[O-].[Na+].C(O)(=O)C>CO>[CH3:19][N:18]1[C@@H:15]2[CH2:16][C:17]3=[CH:1][CH:2]=[C:3]([OH:4])[C:5]4[O:9][C@H:8]5[C:10]([CH2:12][CH2:13][C@@H:14]2[C@:7]5([C:6]=43)[CH2:21][CH2:20]1)=[O:11]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5288826MorphineHCID 10942334Sodium Methoxide

Product 1

HCID 5284570Hydromorphone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
7 °C

Procedure

A 100 mL Schlenk tube was charged with methanol (50 mL), morphine free base (5.0 g, 17.52 mmol) and sodium methoxide (47.4 mg, 0.876 mmol). The mixture was stirred and heated to reflux under nitrogen for 15 min then treated with the solution of the catalyst added by a pipette. The resulting brown solution was stirred and heated to reflux under nitrogen for 1 hour, cooled to 7° C. in an ice bath, treated with acetic acid (0.05 mL, 0.876 mmol), stirred for another 30 min and filtered. The filtered solid was washed with isopropanol (3×8 mL) and dried in an oven at 95° C. to give hydromorphone free base as a white solid. The yield was 4.12 g, 82.4%.

Workup

  1. temperatureheated
  2. temperatureto reflux under nitrogen for 15 min
  3. additionthen treated with the solution of the catalyst
  4. additionadded by a pipette
  5. stirringThe resulting brown solution was stirred
  6. temperatureheated
  7. temperatureto reflux under nitrogen for 1 hour
  8. stirringstirred for another 30 min
  9. filtrationfiltered
  10. washThe filtered solid was washed with isopropanol (3×8 mL)
  11. customdried in an oven at 95° C.

Sources & evidence

ORD record
ord-63a354e5334749928b2603ce0870bd60
Source dataset
uspto-grants-2008_07
Patent number
US07399859B1

Reaction notes

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