Dimethylformamide → 2-(2-Chloro-5-nitrophenyl)oxazole

関与物質

反応手順

To a cloudy suspension of 2-chloro-5-nitrobenzoic acid (1.0 g, 4.96 mmol) and DMF (0.019 mL, 0.25 mmol) in DCM (12.4 mL) at 0° C. was added a 2M solution of oxalyl chloride in DCM (2.98 mL, 5.95 mmol). The resulting suspension was stirred for 1 hour at room temperature. The reaction mixture was concentrated in vacuo and azeotroped with toluene to remove HCl and oxalyl chloride. The residue was dissolved in tetramethylenesulfone (12.4 mL), to which potassium carbonate (1.37 g, 9.92 mmol) and 1H-1,2,3-triazole (0.29 mL, 4.96 mmol) were added. The mixture was heated to 150° C. under nitrogen for 1 hour. The mixture was cooled and diluted with EtOAc and water. The layers were separated, and the aqueous phase extracted three times with EtOAc (50 mL). The organics were combined, washed with water and brine, and then dried over anhydrous magnesium sulfate. Filtration and concentration afforded a dark brown oil which was dissolved in a small amount of DCM and charged to a 80 g silica gel cartridge which was eluted at 65 mL/min. with a 25 min. gradient from 100% to 50% EtOAc/hexanes (monitoring at 254 nm). Concentration of the appropriate fractions afforded Intermediate 56A (0.431 g, 39% yield) as a light yellow solid. HPLC: Rt=3.246 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=225.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 (1H, d, J=2.77 Hz), 8.42 (1H, s), 8.33 (1H, dd, J=8.81, 2.77 Hz), 7.95 (1H, d, J=8.81 Hz), 7.56 (1H, s).

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