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

HRID 1281682ノート

反応式

HRID 1281682 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a3562e47cad445338bf7a6a8912668f3
出典データセット
uspto-grants-2002_09
特許番号
US06455507B1

反応ノート

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