Pyridine, hydrofluoride (1:1) → HCID 178442229, 화합물

HRID 216370

반응식

HRID 216370 반응식
[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

참가 물질

5

반응물 3

HCID 64774Pyridine, hydrofluoride (1:1)HCID 124478981-(Trimethylsilyl)ethanolHCID 178442230HCID 178442230, 화합물

생성물 1

HCID 178442229HCID 178442229, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7794859a89cc42cd8d60fda8cc4b6b72
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193228B2

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