| 56% |
With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 17h; |
A round bottom flask was charged with 4-bromo-1H-imidazole (3.83 g, 26.0 mmol), copper(I) iodide (0.331 g, 1.736 mmol), quinolin-8-ol (0.252 g, 1.736 mmol), cesium carbonate (11.31 g, 34.7 mmol), and <strong>[103962-05-6]1-iodo-4-(trifluoromethoxy)benzene</strong> (2.72 mL, 17.36 mmol). A 10:1 mixture of DMF (50 mL) and water (5.0 mL) were added to the reaction mixture, and the solution was heated to 130C overnight. After stirring 17 h, LC-MS indicated reaction completion. The reaction mixture was cooled to room temperature, was diluted with EtOAc, and was transferred to a separatory funnel with the aid of water. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with saturated aqueous sodium bicarbonate and then ammonium chloride, were dried overNa2SO4/magnesium sulfate (MgSO4) and were concentrated in vacuo. Purification of the residue by normal-phase high-performance liquid chromatography, eluting with 0 - 10% methanol-DCM afforded the title compound as an off-white solid (3.01 g, 56%):1H NMR (400 MHz, CDCl3) d 7.70 (d, J = 1.6 Hz, 1H), 7.41 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 8.9 Hz, 2H), 7.24 (d, J = 1.5 Hz, 1H);19F NMR (376 MHz, CDCl3) d - 58.05; ESIMS m/z 307 ([M+H]+). |
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With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 4h; |
Example 19; Preparation of 4-bromo-1-(4-trifluoromethoxyphenyl)-1H-imidazole A round bottom flask was charged with 4-bromoimidazole (1.15 g, 7.81 mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol), cesium carbonate (3.39 g, 10.4 mmol) and 4-trifluoromethoxyiodobenzene (1.50 g, 5.21 mmol). A 10:1 mixture of DMF (15 mL) and H2O (1.5 mL) were added to the reaction mixture, and the solution was heated to 130 C. for 4 h. The reaction mixture was then diluted with EtOAc and washed sequentially with water, ammonium chloride (saturated), water and sodium bicarbonate. The organics were dried over MgSO4, filtered and purified on a reverse phase column to give 820 mg of imidazole as a white solid. MS 308.0 (M+H); mp 139-141 C. |
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With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 4h; |
A round bottom flask was charged with 4-bromoimidazole (1.15 g, 7.81 mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol), cesium carbonate (3.39 g, 10.4 mmol) and 4-trifluoromethoxyiodobenzene (1.50 g, 5.21 mmol). A 10:1 mixture of DMF (15 mL) and H2O (1.5 mL) was added to the reaction mixture, and the solution was heated to 130 0C for 4 h. The reaction mixture was then diluted with EtOAc and washed sequentially with H2O, ammonium chloride (NH4Cl, saturated), H2O and sodium bicarbonate (NaHCO3). The organics were dried over MgSO4, filtered and purified by reverse phase column chromatography to give the imidazole (820 mg) as a white solid: mp 139-141 0C; ESIMS m/z 308.0 (M+H). |
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