Dimethylformamide → (3-Chloro-2-nitrophenyl)(m-tolyl)methanone

Participants

Reaction Steps

A 200 mL round-bottomed flask was charged with 3-chloro-2-nitrobenzoic acid (2.5 g, 12.40 mmol) and tetrahydrofuran (50 mL). Oxalyl chloride (1.194 mL, 13.64 mmol) was added slowly followed by DMF (0.096 mL, 1.240 mmol). The reaction mixture was stirred at room temperature for 2 hrs. After cooling to 0° C., a 1M solution of m-tolylmagnesium bromide (24.81 mL, 24.81 mmol) was added. After 1 hr, another portion of m-tolylmagnesium bromide (24.81 mL, 24.81 mmol) was added. After a further hour, the reaction mixture was partitioned between ethyl acetate (200 mL) and 1N HCl (150 mL). The aqueous layer was back extracted with ethyl acetate (2×100 mL). The combined organic phases were dried with Na2SO4, filtered and concentrated. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 0% to 100% solvent A/B=ethyl acetate/heptane, REDISEP® SiO2 120 g). Concentration of the appropriate fractions provided Intermediate A-10A (0.700 g, 21%). 1H NMR (400 MHz, DMSO-d6) δ 8.04 (dd, J=8.1, 1.1 Hz, 1H), 7.82 (t, J=7.9 Hz, 1H), 7.71 (dd, J=7.7, 1.1 Hz, 1H), 7.66-7.54 (m, 3H), 7.52-7.46 (m, 1H), 2.40 (s, 3H).

Provenance & Evidence