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

HRID 216370Notes

Reaction equation

HRID 216370 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

HCID 178442229HCID 178442229, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7794859a89cc42cd8d60fda8cc4b6b72
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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