Pyridine, hydrofluoride (1:1) → HCID 178442229、化合物

HRID 216370

反応式

HRID 216370 の反応式
[CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][C:4]1[N:5]=[C:6]([CH2:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][N:20]=3)=[CH:15][CH:14]=2)(O)[CH3:11])[NH:7][CH:8]=1.C1C=CN=CC=1.[FH:34].C[Si](C(O)C)(C)C>C(Cl)Cl>[CH3:1][C:2]([CH3:27])([CH3:26])[CH2:3][C:4]1[N:5]=[C:6]([CH2:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][N:20]=3)=[CH:15][CH:14]=2)([F:34])[CH3:11])[NH:7][CH:8]=1

参加物

5

反応物 3

HCID 64774Pyridine, hydrofluoride (1:1)HCID 124478981-(Trimethylsilyl)ethanolHCID 178442230HCID 178442230、化合物

生成物 1

HCID 178442229HCID 178442229、化合物

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

1-[4-(2,2-dimethylpropyl)-1H-imidazol-2-yl]-2-[4-(5-fluoropyridin-2-yl)phenyl]propan-2-ol (250 mg, 0.68 mmol) in a minimal volume of methylene chloride was added to HF-pyridine (0.5 mL). After stirring at ambient temperature for 1 h, the reaction was added dropwise to trimethylsilylethanol at 0° C. and concentrated in vacuo azeotroping with toluene. The residue was partitioned between ethyl acetate and 1 M aqueous sodium hydroxide. The organic phase was washed with brine, dried (sodium sulfate) and concentrated in vacuo. High pressure liquid chromatography (Chiralcel AD column) eluting with 20% isopropanol/heptane afforded the separate enantiomers. 1H NMR (500 MHz, CDCl3) δ 8.52 (d, J=2.7 Hz, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.69 (dd, J=4.3, 8.7 Hz, 1 h), 7.48-7.42 (m, 3h), 6.62 (s, 1H), 3.39 (d, J=25.4 Hz, 1H), 2.39 (s, 2H), 1.68 (d, J=22.8, 3H), 0.86 (s, 9H).

後処理

  1. concentrationconcentrated in vacuo
  2. customazeotroping with toluene
  3. customThe residue was partitioned between ethyl acetate and 1 M aqueous sodium hydroxide
  4. washThe organic phase was washed with brine
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. washHigh pressure liquid chromatography (Chiralcel AD column) eluting with 20% isopropanol/heptane
  8. customafforded the separate enantiomers

出典と根拠

ORDレコード
ord-7794859a89cc42cd8d60fda8cc4b6b72
出典データセット
uspto-grants-2012_06
特許番号
US08193228B2

関連ノート

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