Reaction Steps
A flask is charged with 3-(6-trifluoromethanesulfonyloxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester (0.225 g, 0.520 mmol), 4-fluorophenylboronic acid (0.145 g, 1.041 mmol), aqueous sodium carbonate (2M, 1.30 mL, 2.60 mmol) and DMF (35 mL). Tetrakis(triphenylphosphine) palladium (0.060 g, 0.052 mmol) is added and the mixture is heated to 150° C. in a sealed tube under microwave irradiation conditions for 12 minutes. The reaction is cooled to room temperature, diluted with water and extracted with dichloromethane. The organic phase is dried with Na2SO4, filtered, and concentrated to give a residue, which is purified by silica gel chromatography (hexanes-ethyl acetate mixtures) to give 3-[6-(4-fluoro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester. MS: (ESI) m/z 379.2 (M+H)+. 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 3-[6-(4-fluoro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 1.45 (d, J=6.3 Hz, 3 H), 1.47 (d, J=6.3 Hz, 3 H), 1.75-1.86 (m, 1 H), 1.93-2.02 (m, 1 H), 2.31-2.47 (m, 2 H), 2.99 (ddd, J=17.0, 9.3, 5.6 Hz, 1 H), 3.13 (dt, J=17.0, 5.3 Hz, 1 H), 5.36 (sept, J=6.3 Hz, 1 H), 6.61 (t, J=5.1 Hz, 1 H), 7.19-7.25 (m, 3 H), 7.51 (dd, J=8.1, 2.0 Hz, 1 H), 7.57 (s, 1 H), 7.66-7.72 (m, 2 H), 8.34 (d, J=1.5 Hz, 1 H), 8.65 (d, J=1.3 Hz, 1 H).
