Phosphoric Acid → Nalbuphine

HRID 533702Notes

Reaction equation

HRID 533702 reaction equation
[CH2:1]1[CH2:4][CH:3]([CH2:5][N:6]2[C@@H:16]3[CH2:17][C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[C:20]5[O:25][C@H:10]6[C:11]([CH2:13][CH2:14][C@:15]3([OH:26])[C@:9]6([C:19]=45)[CH2:8][CH2:7]2)=[O:12])[CH2:2]1.P(=O)(O)(O)O.[H][H]>CC(O)C.O.[Pt]>[CH:23]1[C:18]2[CH2:17][C@H:16]3[N:6]([CH2:5][CH:3]4[CH2:4][CH2:1][CH2:2]4)[CH2:7][CH2:8][C@:9]45[C@H:10]([C@@H:11]([OH:12])[CH2:13][CH2:14][C@@:15]34[OH:26])[O:25][C:20]([C:19]=25)=[C:21]([OH:24])[CH:22]=1

Participants

7

Reactant 3

HCID 1004Phosphoric Acid2×HCID 444650036-KetonalbuphineHCID 178418361HCID 178418361, compound

Product 1

HCID 5311304NalbuphineYield 97.5%

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

6-ketonalbuphine (40 g, 112.8 mmoles) was dissolved in a mixture of IPA (200 mls) and water (200 mls) containing orthophosphoric acid (1.56 mls). The pH of the reaction mixture was 6.49. The reaction mixture was hydrogenated at 40 psi hydrogen gas and 50° C. in the presence of 10% Platinum on carbon catalyst (2.4 g, 0.56 mmoles Pt). After 7 hours, the pH of the reaction mixture is adjusted with orthophosphoric acid (6.25 mls) and filtered. Ammonia solution (25 mls) was added to bring the pH to 8.5-9.0 and the precipitate filtered, washed with 50% aqueous IPA (60 mls), and dried to provide 39.33 g (97% theory) of Nalbuphine alkaloid of purity 95.6% by HPLC.

Workup

  1. filtrationfiltered
  2. additionAmmonia solution (25 mls) was added
  3. filtrationthe precipitate filtered
  4. washwashed with 50% aqueous IPA (60 mls)
  5. customdried

Sources & evidence

ORD record
ord-271f382689a44cd3960f1f091812bf07
Source dataset
uspto-grants-2014_10
Patent number
US08853402B2

Reaction notes

Loading…