Diethyl Ether → 2-[3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazol-4-yl]-propan-2-ol

Participants

Reaction Steps

To a solution of 3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester (300 mg, 0.98 mmol), which can be prepared as described in Example 18, in THF (10 mL) at 0° C. is added a 3.0 M solution of methylmagnesium bromide in diethyl ether (1.63 mL, 4.9 mmol). After one hour of stirring the reaction is quenched with saturated aqueous NH4Cl. The reaction is extracted three times with ethyl acetate and the organic extracts are combined, washed with brine, dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:5) to afford 2-[3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazol-4-yl]-propan-2-ol; HRMS: (ESI) m/z 307.1628 [(M+H)+: Calcd for C17H21N2OF2: 307.1622]; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (d, J=2.53 Hz, 3 H), 1.29 (d, J=3.28 Hz, 3 H), 1.79 (s, 6 H), 6.16 (d, J=3.79 Hz, 1 H), 6.89 (s, 1 H), 7.03 (s, 1 H), 7.33-7.41 (m, 1 H), 7.47-7.59 (m, 2 H), 7.62-7.72 (m, 1 H).

Provenance & Evidence