2,2-dimethyl-1,3-dihydroinden-1-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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). is then placed at room temperature to stir for 10 minutes the layers are separated The organic layer is washed with brine back-extracted with diethyl ether dried with MgSO4 filtered concentrated The resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 15:85 to 1:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-dimethyl-indan-1-ol (3.5 g, 21.6 mmol) in THF (160 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 4.1 g, 32.3 mmol), and triphenylphosphine (9.09 g, 34.5 mmol). The reaction is cooled to 0° C. and diisopropyl azodicarboxylate (6.67 mL, 34.5 mmol) is added. After one hour the reaction is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1) to provide 3-(2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester. HRMS: (ESI) m/z 271.1440 [(M+H)+: Calcd for C16H19N2O2: 271.1447]; 1H NMR (400 MHz, CDCl3) δ ppm 2.60-3.08 (m, 2 H), 3.92 (s, 3 H), 6.25 (s, 1 H), 7.03 (s, 1 H), 7.15-7.46 (m, 4 H), 7.80 (d, J=1.0 Hz, 1 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-(2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester. The layers are separated the organic layer is dried with Na2SO4 filtered concentrated The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,2-dimethyl-indan-1-one, which can be prepared as described in Ranu, B. C.; Jana, U. Journal of Organic Chemistry, 1999, 64, 6380-6386, (13.0 g, 81.3 mmol) in methanol (200 mL) at −20° C. is added NaBH4 (3.07 g, 81.3 mmol). Upon complete consumption of the starting ketone, as determined by TLC analysis, the reaction is quenched with saturated aqueous NH4Cl. The reaction mixture is then concentrated to near dryness, diluted with ethyl acetate and washed with water. The organic layer is then dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:8) to provide 2,2-dimethyl-indan-1-ol. 1H NMR (400 MHz, CDCl3) δ ppm 1δ ppm 1.05 (s, 3 H), 1.20 (s, 3 H), 2.56-2.89 (m, 2 H), 4.70 (s, 1 H), 7.16-7.26 (m, 3 H), 7.35-7.42 (m, 1 H). Upon complete consumption of the starting ketone the reaction is quenched with saturated aqueous NH4Cl The reaction mixture is then concentrated diluted with ethyl acetate washed with water The organic layer is then dried with Na2SO4 filtered concentrated The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:8)