Hydrochloric Acid → Bis(1,1-dimethylethyl)(3-{[3-cyano-5-(methyloxy)phenyl]oxy}-2-fluoro-4-nitrophenyl)propanedioate

Participants

Reaction Steps

Di-tert-butyl malonate (11.22 g, 51.9 mmol) was added dropwise. to a 0° C. solution of NaH (5.09 g, 127 mmol) in THF (150 ml). The reaction mixture was allowed to warm to RT, stirred for an additional 30 mins, and cooled to 0° C. A solution of 3-[(2,3-difluoro-6-nitrophenyl)oxy]-5-(methyloxy)benzonitrile (14.44 g, 47.2 mmol) in THF (50 mL) was added slowly and the reaction mixture was stirred at RT overnight. Dilute HCl was carefully added and the solution was extracted with EtOAc (3×100 mL). The organic layer was dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography (0-35% EtOAc/hexanes) to afford the title compound (22.9 g, 97%) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.88 (dd, J=8.79, 1.46 Hz, 1H) 7.62 (dd, J=8.65, 6.46 Hz, 1H) 6.92 (s, 1H) 6.68-6.79 (m, 2 H) 4.81 (s, 1H) 3.83 (s, 3H) 1.49 (s, 16H).

Provenance & Evidence