Morphine → Hydromorphone

HRID 748602Notes

Reaction equation

HRID 748602 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]>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

3

Reactant 1

HCID 5288826Morphine2×

Product 1

HCID 5284570Hydromorphone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
7 °C

Procedure

A 1 L round bottom flask equipped with return condenser and nitrogen inlet was charged with methanol (650 mL) and morphine free base (50.0 g, 175.2 mmol). The mixture was stirred magnetically and heated to reflux under nitrogen until all morphine dissolves (45 min) then treated with the solution of the catalyst added via a cannula. The resulting brown solution was stirred and heated to reflux under nitrogen for 1 hour, then volume of the mixture was reduced to ca 400 mL by distillation. The resulting slurry was cooled to 7° C. in an ice bath, stirred at this temperature for 1 hour and filtered. The filtered solid was washed with isopropanol (3×60 mL) and dried in an oven at 95° C. to give hydromorphone free base as a white solid. The yield was 41.71 g, 83.4%.

Workup

  1. customA 1 L round bottom flask equipped with return condenser and nitrogen inlet
  2. temperatureheated
  3. dissolutiondissolves (45 min)
  4. additionthen treated with the solution of the catalyst
  5. additionadded via a cannula
  6. stirringThe resulting brown solution was stirred
  7. temperatureheated
  8. temperatureto reflux under nitrogen for 1 hour
  9. distillationvolume of the mixture was reduced to ca 400 mL by distillation
  10. stirringstirred at this temperature for 1 hour
  11. filtrationfiltered
  12. washThe filtered solid was washed with isopropanol (3×60 mL)
  13. customdried in an oven at 95° C.

Sources & evidence

ORD record
ord-2ec48c035504404486c743731d2e44d6
Source dataset
uspto-grants-2008_07
Patent number
US07399859B1

Reaction notes

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