Oxalyl chloride → 7-chloro-1-(2-chloro-phenyl)-3-methyl-1H-quinolin-4-one

Participants

Reaction Conditions

Reaction Steps

To a 3-necked, 100 mL round-bottom flask was added DMF (26 mL) which was then cooled to −4° C. To the reaction was slowly added oxalyl chloride (2.8 g, 1.93 mL, 22.1 mmol) dropwise. Once the addition was complete, the reaction was warmed to room temperature. To the above mixture was added 1-[4-chloro-2-(2-chloro-phenylamino)-phenyl]-propan-1-one (1.3 g, 4.42 mmol) in DMF (10 mL). The reaction mixture was heated to 130° C. After 2 hr, HPLC showed a 35:65 product to SM ratio. The reaction was heated overnight at 130° C. HPLC the next day showed a 1:1 mixture of product to SM. The reaction mixture was poured over ice. Once the ice melted, the solids were filtered off. The recovery of solids was low so the filtrate was extracted with ethyl acetate. The combined organic layers were washed with water and brine, then dried over magnesium sulfate, filtered, and concentrated. The crude (˜900 mg) was purified by flash chromatography (silica gel, 80 g, 0-40% ethyl acetate in hexanes). The starting material of 1-[4-chloro-2-(2-chloro-phenylamino)-phenyl]-propan-1-one (694 mg 53.4%) was recovered as a yellow oil. The desired product 7-chloro-1-(2-chloro-phenyl)-3-methyl-1H-quinolin-4-one (200 mg, 14.9%) of 7-chloro-1-(2-chloro-phenyl)-3-methyl-1H-quinolin-4-one was obtained as a red solid. 1H NMR (DMSO-d6) δ ppm (d, J=8.7 Hz, 1H) 7.97 (d, J=0.6 Hz, 1H) 7.82 (dd, J=7.8, 1.7 Hz, 1H) 7.76 (dd, J=7.5, 2.0 Hz, 1H) 7.56-7.73 (m, 2H) 7.40 (dd, J=8.6, 1.9 Hz, 1H) 6.63 (d, J=1.8 Hz, 1H) 1.98 (s, 3H). MS calcd. for C16H11Cl2NO [(M+H)+] 305.0, obsd. 304.0.

Provenance & Evidence