4-chloro-2-(2-chloro-phenylamino)-N-methoxy-N-methyl-benzamide → 1-[4-Chloro-2-(2-chloro-phenylamino)-phenyl]-propan-1-one

Participants

Reaction Conditions

Reaction Steps

In a 500 mL round bottom flask, 4-chloro-2-(2-chloro-phenylamino)-N-methoxy-N-methyl-benzamide (1.0 g, 3.08 mmol) was added to THF (60 mL) to give a colorless solution. The reaction was cooled to 0° C. in an ice bath and ethyl magnesium bromide (3.0 M in THF, 3.59 mL, 10.8 mmol) was added slowly dropwise. The mixture was stirred at 0° C. for 1 hr. TLC and HPLC indicated the presence of starting material. The reaction was warmed to room temperature overnight. TLC the next day still showed the presence of starting material. The reaction was re-cooled to 0° C. and additional amount of ethylmagnesium bromide (3.59 mL, 10.8 mmol) was added. The reaction was stirred at 15° C. for 2.5 hr. TLC indicated complete consumption of starting material. The reaction mixture was quenched with cold water and extracted twice with ethyl acetate. The combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated. The crude material was purified by flash chromatography using 0-20% dichloromethane-hexanes to give 1-[4-chloro-2-(2-chloro-phenylamino)-phenyl]-propan-1-one (584 mg, 65% yield) as a yellow oil. 1H NMR (DMSO-d6) δ ppm 10.67 (s, 1H) 8.05 (d, J=8.7 Hz, 1H) 7.58 (ddd, J=12.8, 8.1, 1.1 Hz, 2H) 7.32-7.48 (m, 1H) 7.12-7.27 (m, 1H) 7.02 (d, J=2.0 Hz, 1H) 6.91 (dd, J=8.6, 1.9 Hz, 1H) 3.10 (q, J=7.3 Hz, 2H) 1.09 (t, J=7.2 Hz, 3H). MS calcd. for C15H13Cl2NO [(M+H)+] 295.0, obsd. 294.1.

Provenance & Evidence