Toluene → 1-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole

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Reaction Steps

To a solution of 2,2-dimethyl-indan-1-ol, prepared as described in Example 10, (400 mg, 2.47 mmol) in THF (30 mL) at 0° C. is added 5-trifluoromethyl-1H-imidazole (510 mg, 3.75 mmol), triphenylphosphine (982 mg, 3.75 mmol) and a 40 wt % solution of dimethyl azodicarboxylate in toluene (1.4 mL, 3.75 mmol). The reaction is then placed at room temperature and permitted to stir for 1 hour, at which time it is diluted with diethyl ether and water, and is then charged with Na2CO3 (1.9 g, 17.9 mmol). The reaction is permitted to stir for 10 minutes and the layers are separated. The organic layer is washed with brine and the aqueous layers are combined and back-extracted with diethyl ether. The organic layers are combined, dried with MgSO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 15:85 to 1:1) to afford 1-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole; HRMS: (ESI) m/z 281.1266 [(M+H)+; calcd for C15H15F3N3: 281.1276]. The HCl salt of the title compound can be prepared by dissolution in diethyl ether, followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 1-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole; 1H NMR (400 MHz, CD3OD) δ ppm 0.91 (s, 3 H), 1.29 (s, 3 H), 2.83-3.24 (m, 2 H), 5.46 (s, 1 H), 7.25-7.50 (m, 4 H), 8.12 (s, 1 H), 8.18 (s, 1 H).

Provenance & Evidence