Benzyl Bromide → 3-O-Benzylnaltrexone

HRID 488059Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 488059
[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

Komponenten

6

Edukt 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 5360515Naltrexone

Produkt 1

HCID 57485153-O-BenzylnaltrexoneAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-e3e17c3a693c4b189bb087341a95a0fb
Quelldatensatz
uspto-grants-1994_03
Patentnummer
US05298622

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