Hydrochloric Acid → HCID 57781093, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-cyclopropyl-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one (2.25 g, 9.72 mmol) in THF (100 mL) is added triphenylphosphine (4.3 g, 16.5 mmol), and methyl-4-imidazolecarboxylate (2.08 g, 16.5 mmol). The heterogeneous reaction mixture is cooled to 0° C. and di-tert-butyl azodicarboxylate (3.81 g, 16.5 mmol) is added. The reaction is allowed to warm to room temperature and stirred for 45 min, and then heated at 44° C. for an additional 75 min, at which time the reaction is cooled to 0° C. and 4M HCl in dioxane (20 mL, 80 mmol) is added. The reaction is brought to room temperature and allowed to stir for 1 h. The reaction mixture is then basified to a pH of ca. 9 via the cautious addition of saturated aqueous NaHCO3. The resulting mixture is further diluted with ethyl acetate and saturated aqueous NaHCO3, and the layers are separated. The aqueous layer is extracted three times with ethyl acetate and the organic layers are combined, dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue is adsorbed onto silica gel and submitted to silica gel flash chromatography (ethyl acetate-dichloromethane, 1:24 to 1:4) to provide 3-(2-cyclopropyl-3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester as an off-white solid; HRMS (ESI) m/z 340.1668 [(M+H)+; calculated for C19H22N3O3: 340.1661]; 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.34-0.45 (m, 1 H), 0.78-0.88 (m, 1 H), 0.90-0.99 (m, 1 H), 1.05-1.16 (m, 1 H), 1.31 (s, 3 H), 1.45 (s, 3 H), 2.29-2.43 (m, 1 H), 3.94 (s, 3 H), 6.55 (s, 1 H), 7.28-7.33 (m, 2 H), 7.44-7.55 (m, 2 H), 7.78 (s, 1 H), 8.17-8.29 (m, 1 H)

Provenance & Evidence