N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide → 1-(2-Phenylamino-6-trifluoromethyl-pyridin-3-yl)-propan-1-one

Participants

Reaction Conditions

Reaction Steps

In a 250 mL round-bottomed flask, N-methoxy-N-methyl-2-phenylamino-6-trifluoromethyl-nicotinamide (1.73 g, 5.32 mmol) was combined with THF (20 mL) to give a brown solution and the solution was cooled to 0° C. Ethylmagnesium bromide (1.0 M in THF) (16 mL, 16.0 mmol) was added dropwise at 0° C. over 5 min. The reaction mixture was stirred in an ice bath for 2.5 hr and 1 hr at room temperature. Additional ethylmagnesium bromide (1.0 M in THF) (6 mL, 6.00 mmol) was introduced over 3 min and the mixture was stirred for 2 hr at room temperature. The reaction mixture was cautiously quenched with water (50 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, washed with brine (1×50 mL), dried over MgSO4 and concentrated in vacuo to give 1.56 g of crude product as a yellow solid. The crude material was purified by flash chromatography (silica gel, 150 g, 15% ethyl acetate in hexanes) to give 1-(2-phenylamino-6-trifluoromethyl-pyridin-3-yl)-propan-1-one (1.35 g, 86.3% yield) as a yellow solid. 1H NMR (DMSO-d6) δ ppm 11.13 (s, 7H) 8.67 (d, J=8.2 Hz, 1H) 7.74 (d, J=7.8 Hz, 2H) 7.20-7.54 (m, 3H) 6.81-7.19 (m, 1H) 3.19 (q, J=7.2 Hz, 2H) 1.12 (t, J=7.1 Hz, 3H). MS calcd. for C15H13F3N2O [(M+H)+] 295.0, obsd. 295.0.

Provenance & Evidence