Hydrochloric Acid → 3-[(2,3-Difluoro-6-nitrophenyl)oxy]-5-(methyloxy)benzonitrile

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Reaction Steps

NaH (2.05 g, 51.2 mmol) was added portionwise to a 0° C. solution of 3-hydroxy-5-(methyloxy)benzonitrile (7.63 g, 51.2 mmol) (prepared following the procedure in Magano et al. J. Org. Chem. 2006, 71, 7103) in THF (205 ml). When addition was complete, the thick suspension was stirred at this temperature for another 30 mins, and trifluoronitrobenzene (9.51 g, 53.7 mmol) was then added. The reaction mixture was stirred at RT for 3 h, dilute HCl was added and the solution was extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-30% EtOAc/hexanes) to afford the title compound (14.44 g, 92%) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.96 (ddd, J=9.36, 4.97, 2.24 Hz, 1H) 7.28-7.35 (m, 1H) 6.95 (d, J=0.73 Hz, 1H) 6.78 (t, J=2.15 Hz, 1H) 6.73 (s, 1H) 3.85 (s, 3H).

Provenance & Evidence