Hydrochloric Acid → 1-(2,2-Dimethyl-3,3-difluoro-indan-1-yl)-5-imidazolecarboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 3,3-difluoro-2,2-dimethyl-indan-1-ol (388 mg, 1.96 mmol) in THF (16 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 370 mg, 2.94 mmol), and triphenylphosphine (770 mg, 2.94 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (670 mg, 2.94 mmol) is added. The reaction is placed at room temperature and permitted to stir for six hours and then is heated to 40° C. overnight. The next day the reaction mixture is cooled to 0° C. and quenched with 4 N HCl in dioxane (5 mL, 20 mmol) and stirred for 30 minutes. The reaction is concentrated to near dryness and diluted with ethyl acetate. The organic layer is extracted three times with 1 N aqueous HCl. The aqueous extracts are combined, neutralized with Na2CO3, and extracted three times with ethyl acetate. The combined organic layers are 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 furnish 3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester. MS: (ESI) m/z 307.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.87 (d, J=2.5 Hz, 3 H), 1.33 (d, J=3.0 Hz, 3 H), 3.96 (s, 3 H), 6.43 (d, J=2.8 Hz, 1 H), 7.17 (s, 1 H), 7.30-7.37 (m, 1 H), 7.56-7.64 (m, 2 H), 7.69-7.76 (m, 1 H), 7.85 (s, 1 H)

Provenance & Evidence