Methyl iodide → 4-imidazol-1-yl-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one

Participants

Reaction Steps

To a solution of 4-imidazol-1-yl-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one, which can be prepared as described in Example 36d (140 mg, 0.58 mmol) in DMF (8 mL) at −10° C. is added NaH [60% dispersion in oil (30 mg, 0.75 mmol)]. After 10 min, the reaction is warmed to room temperature for 5 min and then re-cooled to −10° C. The reaction is then charged with methyl iodide (0.075 mL, 1.2 mmol) and placed at room temperature. After 20 min, the reaction is cooled to −10° C., quenched with saturated aqueous NH4Cl, and diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the aqueous layer is extracted two times with ethyl acetate. The combined organic layers are dried over Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:12) to afford 4-imidazol-1-yl-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one; HRMS (ESI) m/z 256.1448 [(M+H)+: Calcd for C15H18N3O: 256.1450]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22 (s, 3 H), 1.33 (s, 3 H), 3.09 (s, 3 H), 5.01 (s, 1 H), 6.78 (s, 1 H), 7.02 (s, 1 H), 7.20 (d, J=3.8 Hz, 1 H), 7.47-7.57 (m, 3 H), 8.20-8.28 (m, 1 H).

Provenance & Evidence