Imidazole → (3s,5s,6r)-5,6-Dichloro-1-(6-(((tert-butyldimethylsilyl)oxy)methyl)-tetrahydro-5-hydroxy-2h-pyran-3-yl)-1h-benzimidazole

HRID 1281682Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1281682
[Cl:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]2[N:6]([C@H:9]3[CH2:14][C@H:13]([OH:15])[C@@H:12]([CH2:16][OH:17])[O:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.CN(C=O)C.N1C=CN=C1.[Si:31](Cl)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>O>[Cl:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]2[N:6]([C@H:9]3[CH2:14][C@H:13]([OH:15])[C@@H:12]([CH2:16][O:17][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[O:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 57289973(3s,5s,6r)-5,6-Dichloro-1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2h-pyran-3-yl)-1h-benzimidazole

Produkt 1

HCID 56997105(3s,5s,6r)-5,6-Dichloro-1-(6-(((tert-butyldimethylsilyl)oxy)methyl)-tetrahydro-5-hydroxy-2h-pyran-3-yl)-1h-benzimidazoleAusbeute 50 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

To a stirred suspension of (3S,5S,6R)-5,6-dichloro-1-(tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H-pyran-3-yl)-1H-benzimidazole (example 36, 1.50 g, 4.73 mmol) in 15 ML of dry DMF at 0° C. was added imidazole (0.40 g, 5.68 mmol) followed by tert-butyldimethylsilyl chloride (0.81 g, 5.20 mmol). The reaction was allowed to warm to room temperature, stirred overnight then diluted with water (100 ML) and extracted with chloroform (100 ML). The organic layer was dried over sodium sulfate, filtered and the solvents were removed under reduced pressure. Purification by flash chromatography on silica gel 60 eluting with 50% ethyl acetate-hexanes afforded the title compound as a white solid (1.00 g, 50%) along with 0.40 g recovered starting material; m.p. 143-155° C.; 1H-NMR (DMSO-d6, 200 MHz) δ: 8.51, 8.09, 8.00 (s, each 1H), 4.90 (d, J=5.6 Hz, 1H), 4.89 (m, 1H), 4.26 (m, 1H), 3.91 (m, 1H), 3.86 (m, 1H), 3.55-3.42 (m, 1H), 3.32-3.24 (m, 2H), 2.29-2.19 (m, 1H), 1.97-1.83 (m, 1H), 0.91 (s, 9H), 0.97, 0.78 (s, each 3H).

Aufarbeitung

  1. extractionextracted with chloroform (100 ML)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customPurification by flash chromatography on silica gel 60 eluting with 50% ethyl acetate-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-a3562e47cad445338bf7a6a8912668f3
Quelldatensatz
uspto-grants-2002_09
Patentnummer
US06455507B1

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