反应详情

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).

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