Lithium Hydroxide → 2-(4-Fluoro-2-nitroanilino)benzo[b]thiophene-3-carbonitrile

Participants

Reaction Steps

Combine 2-amino-benzo[b]thiophene-3-carbonitrile (3.75 g, 21.5 mmol), 1,4-Difluoro-2-nitro-benzene (2.33 mL, 21.5 mmol), and lithium hydroxide (1.03 g, 43.0 mmol) in anhydrous dimethylsulfoxide (50 mL), and heat at 55° C. for about 5 hours. Cool to ambient temperature, pour into a beaker filled with ice/deionized water (200 mL), and stir for 30 minutes. Isolate the precipitated material by suction filtration, wash the solid with dichloromethane, and dry it under reduced pressure to give the title compound (0.618 g). Add deionized water and ethyl acetate to the filtrate, and then separate the organic layer. Extract the aqueous layer with ethyl acetate many times, and then with dichloromethane many times. Then wash the organics with deionized water (3×). Combine the washes and back extract them with ethyl acetate. Wash the organics with a saturated solution of sodium chloride, and then dry (sodium sulfate), filter, and concentrate the organics under reduced pressure to a dark solid. After triturating with methanol, isolate the resulting solid by suction filtration, wash with methanol, and dry at ambient temperature under reduced pressure to give the title compound (4.422 g). Total solid: 5.04 g (74.8%): Mass spectrum (ES+, m/e): 314 (M+1); NMR (1H, 300 MHz, CDCl3), δ (ppm): 9.96 (s, 1H), 8.06-7.98 (m, 1H), 7.85-7.77 (m, 1H), 7.77-7.69 (m, 1H), 7.68-7.59 (m, 1H), 7.56-7.47 (m, 1H), 7.45-7.34 (m, 2H).

Provenance & Evidence