Benzophenone → Hydromorphone

HRID 496804Notes

Reaction equation

HRID 496804 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(C1C=CC=CC=1)(=O)C1C=CC=CC=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh].C(O)(C)(C)C>[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 2

HCID 3102BenzophenoneHCID 5288826Morphine

Product 1

HCID 5284570HydromorphoneYield 86%

Reagents, catalysts & solvents 2

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)CatalystHCID 6386tert-ButanolSolvent

Procedure

Dried morphine (0.324 g), benzophenone (1.47 g), chlorotris(triphenylphosphine)rhodium (I) (Wilkinson's catalyst) (0.055 g), and tert-butanol (6 mL) were charged into a glass hydrogenation bottle. The bottle was evacuated and filled with hydrogen. The mixture was magnetically agitated at ambient temperature (24–29° C.) at 16 psi for 16 hours. Potassium tert-butylate (0.804 g) was charged into the bottle with the reaction mixture in one portion, the mixture was magnetically agitated until all solids dissolved, then heated under nitrogen at 60° C. for 4.5 hours. After aging for additional 66 hours at ambient temperature the mixture was quenched with 1.5N acetic acid (6 mL) with mixing and cooling in the water bath, diluted with methanol to 250 mL in volumetric flask and assayed by HPLC. Solution contains 1.12 mg/mL hydromorphone (86% yield), purity 94 area %.

Workup

  1. customThe bottle was evacuated
  2. additionfilled with hydrogen
  3. additionPotassium tert-butylate (0.804 g) was charged into the bottle with the reaction mixture in one portion
  4. stirringthe mixture was magnetically agitated until all solids
  5. dissolutiondissolved
  6. temperatureheated under nitrogen at 60° C. for 4.5 hours
  7. waitAfter aging for additional 66 hours at ambient temperature
  8. customthe mixture was quenched with 1.5N acetic acid (6 mL)
  9. additionwith mixing
  10. temperaturecooling in the water bath
  11. additiondiluted with methanol to 250 mL in volumetric flask

Sources & evidence

ORD record
ord-f57c926cc9f34ea387b5483779cc827b
Source dataset
uspto-grants-2005_09
Patent number
US06946556B1

Reaction notes

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