Naloxone → 14-Hydroxymorphine-6-one

HRID 2275307Notes

Reaction equation

HRID 2275307 reaction equation
C=C[CH2:3][N:4]1[C@@H:21]2[CH2:22][C:9]3[CH:10]=[CH:11][C:12]([OH:24])=[C:13]4[O:14][C@H:15]5[C:16]([CH2:18][CH2:19][C@:20]2([OH:23])[C@:7]5([C:8]=34)[CH2:6][CH2:5]1)=[O:17]>ClCCl>[CH3:3][N:4]1[C@@H:21]2[CH2:22][C:9]3[CH:10]=[CH:11][C:12]([OH:24])=[C:13]4[O:14][C@H:15]5[C:16]([CH:18]=[CH:19][C@:20]2([OH:23])[C@:7]5([C:8]=34)[CH2:6][CH2:5]1)=[O:17]

Participants

3

Reactant 1

HCID 5284596Naloxone3×

Product 1

HCID 1528625314-Hydroxymorphine-6-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Naloxone (compound (104)) is contacted with an allyl scavenger, e.g., N,N-dimethyl barbituric acid (compound (146)), and a transition metal catalyst, e.g., tetrakis(triphenylphosphine)palladium[0], in dichloromethane at a temperature of about 20° C. Naloxone as a suspension in dichloromethane is added, and the resulting mixture stirred overnight at a temperature within the range of from about 10° C. to about 70° C., or from about 20° C. to about 60° C., or from about 30° C. to about 60° C. The mixture is cooled and the solids collected by filtration, washed with dichloromethane, and then washed with water. The washed solids are dissolved in aqueous acid (e.g., 10:1 water:concentrated sulfuric acid) at a temperature within the range of from about 10° C. to about 70° C., or from about 20° C. to about 60° C., or from about 30° C. to about 60° C., and the solution washed with dichloromethane before being basified to a pH within the range of from about pH 8 to about pH 10, e.g., using 28% ammonium hydroxide. The solids are collected by filtration and dried to provide the desired product, noroxymorphone (see, e.g., Example 7).

Workup

  1. customat a temperature of about 20° C
  2. customfrom about 20° C. to about 60° C.
  3. customfrom about 30° C. to about 60° C
  4. temperatureThe mixture is cooled
  5. filtrationthe solids collected by filtration
  6. washwashed with dichloromethane
  7. washwashed with water
  8. dissolutionThe washed solids are dissolved in aqueous acid (e.g., 10:1 water:concentrated sulfuric acid) at a temperature within the range of from about 10° C. to about 70° C.
  9. washfrom about 20° C. to about 60° C., or from about 30° C. to about 60° C., and the solution washed with dichloromethane
  10. filtrationThe solids are collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-8347db7fc184452b95ca881801d89366
Source dataset
uspto-grants-2015_09
Patent number
US09127014B2

Reaction notes

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