(Ethoxycarbonylmethyl)triphenylphosphonium bromide → Ethyl (2E)-3-(4-[(3-chloro-4-fluorophenyl)amino]carbonyl-1,2,5-oxadiazol-3-yl)acrylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (carbethoxymethyl)triphenylphosphonium bromide (3.14 g, 7.32 mmol) in toluene (37 mL) was added sodium tert-butoxide (723 mg, 7.52 mmol) at rt under a nitrogen atmosphere. After stirring for 30 min, a solution of N-(3-chloro-4-fluorophenyl)-4-formyl-1,2,5-oxadiazole-3-carboxamide (811 mg, 3.01 mmol) in THF (10 mL) was cannulated into reaction flask. The resulting solution was heated at 80° C. for 3 h, then cooled to rt overnight. The reaction was quenched with a 1 N HCl solution, the aqueous solution was extracted with ethyl acetate. The combined organic solutions were washed with brine, dried over Na2SO4, filtered and concentrate under reduced pressure. The residue was purified with flash chromatography (30% ethyl acetate/hexane) to give the desired product as a white solid (0.91 g, 89%). 1H NMR (400 MHz, CD3OD): δ 7.92 (m, 2 H), 7.65 (m, 1 H), 7.26 (m, 1H), 7.01 (m, 1 H), 4.27 (m, 2 H), 1.33 (m, 3 H); LCMS for C14H12ClFN3O4(M+H)+: m/z=340.

Provenance & Evidence