Benzyl Bromide → 3-O-Benzylnaltrexone

HRID 488059Notes

Reaction equation

HRID 488059 reaction equation
[CH:1]1[C:6]2[CH2:7][C@H:8]3[N:13]([CH2:14][CH:15]4[CH2:17][CH2:16]4)[CH2:12][CH2:11][C@:10]45[C@H:18]([C:20]([CH2:22][CH2:23][C@@:9]34[OH:24])=[O:21])[O:19][C:4]([C:5]=25)=[C:3]([OH:25])[CH:2]=1.[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH2:17]1[CH:15]([CH2:14][N:13]2[C@@H:8]3[CH2:7][C:6]4[CH:1]=[CH:2][C:3]([O:25][CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)=[C:4]5[O:19][C@H:18]6[C:20]([CH2:22][CH2:23][C@:9]3([OH:24])[C@:10]6([C:5]=45)[CH2:11][CH2:12]2)=[O:21])[CH2:16]1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 5360515Naltrexone

Product 1

HCID 57485153-O-BenzylnaltrexoneYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of naltrexone (2.5 g, 7.3 mmol) and benzylbromide (1.5 g, 8.8 mmol) in DMF (25 mL) was added potassium carbonate (2.8 g, 20 mmol). The mixture was stirred for 12 hrs at 60° C., then cooled and diluted with water. The resulting oily product was extracted with EtOAc. The extract was washed with water dried over MgSO4 and concentrated. The residue was chromatographed on silica gel (hexane-EtOAc, 3;2) to afford 3-benzylnaltrexone (4) (2.3 g, 74%). 1H NMR (CDCl3) δ 0.15(2H, m, H-20β, H-21β), 0.56(2H, m, H-20α, H-21α), 0.87(1H, m, H-19), 1.58(1H, dd, J=12.3 Hz, 2.4 Hz, H-15), 1.64(1H, dt, J=13.5 Hz, 2.4 Hz, H-8), 1.89(1H, d, J= 13.5 Hz, H-8), 2.13(1H, dt, J=12.3 Hz, 2.4 Hz, H-15), 2.30(1H, dt, J=12.3 Hz, 2.4 Hz, H-16), 2.40(3H, m, H-7, H-18), 2.55(1H, dd, J=18.3 Hz, 6.0 Hz, H-10), 2.69(1H, dd, J=12.3 Hz, 2.4Hz, H-16), 3.03(2H, m, H-7, H-10), 3.18(1H, d, J=6.0 Hz, H-9), 4.70(1H, s, H-5), 5.20(1H, d, J=12.0 Hz, Bz CH), 5.29(1H, d, J=12.0 Hz, Bz CH), 6.56(1H, d, J=7.2 Hz, H-1), 6.71(1H, d, J=7.2 Hz, H-2), 7.25-7.60(5H, m, Bz aromatic H).

Workup

  1. temperaturecooled
  2. extractionThe resulting oily product was extracted with EtOAc
  3. washThe extract was washed with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel (hexane-EtOAc, 3;2)

Sources & evidence

ORD record
ord-e3e17c3a693c4b189bb087341a95a0fb
Source dataset
uspto-grants-1994_03
Patent number
US05298622

Reaction notes

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