Methyl iodide → N1-(4-bromo-2-methoxyphenyl)-N1-methyl-3-phenylpropanamide

Participants

Reaction Conditions

Reaction Steps

A solution of N1-(4-bromo-2-methoxyphenyl)-3-phenylpropanamide (1.0 g, 3 mmol) in dimethylformamide (20 mL) at 0° C. was treated with pre-washed (3 times with heptane) sodium hydride (0.158 g, 6.6 mmol). The reaction mixture was stirred for 1 h at 0° C. Methyl iodide (0.511 g, 3.6 mmol) was added drop-wise, and the solution stirred for 15 min at 0° C. The ice bath was removed and the reaction mixture was stirred overnight at room temperature. The reaction did not go to completion over night; additional methyl iodide (0.511 g, 3.6 mmol) was added and the reaction mixture stirred over night. The reaction mixture was quenched with water (30 mL). Ethyl acetate was added, and the layers were partitioned. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting 3:1 heptane:ethyl acetate, and afforded 0.729 g (70%) of N1-(4-bromo-2-methoxyphenyl)-N1-methyl-3-phenylpropanamide. 1H NMR (DMSO-d6, 400 MHz) δ 7.330-7.326 (s, 1H), 7.235-7.178 (m, 2H), 7.161-7.116 (m, 3H), 7.058-7.040 (m, 2H), 3.811 (s, 3H), 3.002 (s, 3H), 2.753-2.708 (m, 2H), 2.282-2.204 (m, 1H), 2.138-2.061 (m, 1H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 7.366 min (96%).

Provenance & Evidence