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

HRID 1281682노트

반응식

HRID 1281682 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a3562e47cad445338bf7a6a8912668f3
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06455507B1

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