Hydrochloric Acid → 3-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,2-dimethyl-2,3-dihydro-benzofuran-3-ol (375 mg, 2.28 mmol) in THF (20 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 432 mg, 3.42 mmol), followed by triphenylphosphine (896 mg, 3.42 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (787 mg, 3.42 mmol) is added. The reaction is permitted to warm to room temperature and stirred for 2 hours. The reaction mixture is then 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-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester; HRMS: (ESI) m/z 245.0934 [(M+H)+: Calcd for C13H13N2O3: 245.0926]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05 (s, 3H), 1.57 (s, 3 H), 3.92 (s, 3 H), 6.32 (s, 1 H), 6.92 (d, J=8.1 Hz, 1 H), 6.95-7.02 (m, 2 H), 7.25 (s, 1 H), 7.32-7.40 (m, 1 H), 7.80 (s, 1 H).

Provenance & Evidence