Imidazole → HCID 59199365, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3,3-dimethyl-indan-1-ol (CAS#38393-92-9, 1.62 g, 1.0 mmol)] in toluene (30 mL) is added imidazole (1.36 g, 20.0 mmol) followed by tri-t-butylphosphine (2.5 mL, 10.1 mmol). The reaction is put at 0° C. and N,N,N′,N′-tetramethylazodicarboxamide (1.72 g, 10 mol) is then added. The reaction is permitted to stir for 10 minutes at 0° C. and then is heated at 60° C. over night. The next morning the reaction is diluted with heptane (30 mL) and filtered. The filtrate is extracted twice with 1 N aqueous HCl. The aqueous extracts are combined, washed with ethyl acetate and then basified (pH>10) by the careful addition of 5 N aqueous NaOH. The aqueous solution is then extracted three times with dichloromethane. The combined organic extracts are dried with Na2SO4. filtered and concentrated. The resulting residue is purified by semi-preparative reverse phase HPLC (15 to 85% acetonitrile/water w/0.1% NH4OH) to afford 1-(3,3-dimethyl-indan-1-yl)-1H-imidazole; HRMS: (ESI) m/z 213.1397 [(M+H)+; calcd for C14H17N2: 213.1392]; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 3 H), 1.42 (s, 3 H), 2.11 (dd, J=12.9, 8.3 Hz, 1 H), 2.57 (dd, J=12.9, 7.6 Hz, 1 H), 5.72 (t, J=8.1 Hz, 1 H), 6.86 (s, 1 H), 7.01 (d, J=8.3 Hz, 1 H), 7.09 (s, 1 H), 7.19-7.29 (m, 2 H), 7.35 (t, J=7.5 Hz, 1 H), 7.62 (s, 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 1-(3,3-dimethyl-indan-1-yl)-1H-imidazole.

Provenance & Evidence