Formic Acid → Nalbuphine

HRID 39327Notes

Reaction equation

HRID 39327 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-4861f219f3db4a8ba91ce262931d1b05
Source dataset
uspto-grants-2013_09
Patent number
US08524904B2

Reaction notes

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