Formic Acid → Nalbuphine

HRID 2390904Notes

Reaction equation

HRID 2390904 reaction equation
C(N(CC)CC)C.C(O)=O.[CH2:11]1[CH2:14][CH:13]([CH2:15][N:16]2[C@@H:26]3[CH2:27][C:28]4[CH:33]=[CH:32][C:31]([OH:34])=[C:30]5[O:35][C@H:20]6[C:21]([CH2:23][CH2:24][C@:25]3([OH:36])[C@:19]6([C:29]=45)[CH2:18][CH2:17]2)=[O:22])[CH2:12]1>C(#N)C.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.Cl[Ru]Cl.Cl[Ru]Cl>[CH:33]1[C:28]2[CH2:27][C@H:26]3[N:16]([CH2:15][CH:13]4[CH2:14][CH2:11][CH2:12]4)[CH2:17][CH2:18][C@:19]45[C@H:20]([C@@H:21]([OH:22])[CH2:23][CH2:24][C@@:25]34[OH:36])[O:35][C:30]([C:29]=25)=[C:31]([OH:34])[CH:32]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 444650036-Ketonalbuphine

Product 1

HCID 5311304NalbuphineYield 83%

Reagents, catalysts & solvents 2

HCID 10908223Dichloro(p-cymene)ruthenium(II) dimerCatalystHCID 6342AcetonitrileSolvent2×

Procedure

Into a dried flask was added triethylamine (0.87 g, 8.6 mmol, 1.2 mL) and acetonitrile (5 mL). To this solution was added >96% HCO2H (0.99 g, 21.5 mmol, 0.81 mL). After stirring under nitrogen for 15 minutes, N-(cyclobutylmethyl)-noroxymorphone (1.02 g, 2.9 mmol) was added. Then, dichloro(p-cymene)ruthenium (II) dimer (10 mg, 0.0163 mmol) followed by (1S,2S)-(+)-N-tosyl-diphenylethylene diamine (12 mg, 0.033 mmol) were added. This reaction was stirred for 72 hours at room temperature. HPLC analysis indicated that the reaction was complete. The reaction mixture was evaporated under reduced pressure forming a thick brown oil. Slurring the oil in acetonitrile (15 mL) for 18 hours yielded a brown solid. The solid was isolated by filtration, which was washed with acetonitrile (10 mL). Drying the solid yielded nalbuphine (0.85 g, 83% yield, 6-α: 99%) as a tan solid.

Workup

  1. additionwere added
  2. stirringThis reaction was stirred for 72 hours at room temperature
  3. customThe reaction mixture was evaporated under reduced pressure
  4. customforming a thick brown oil
  5. customfor 18 hours
  6. customyielded a brown solid
  7. customThe solid was isolated by filtration, which
  8. washwas washed with acetonitrile (10 mL)
  9. customDrying the solid

Sources & evidence

ORD record
ord-dd180f819393492c970d5e6f105ea6eb
Source dataset
uspto-grants-2012_09
Patent number
US08273888B2

Reaction notes

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