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

Temperature

80 °C

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, 2H), 7.65 (m, 1H), 7.26 (m, 1H), 7.01 (m, 1H), 4.27 (m, 2H), 1.33 (m, 3H); LCMS for C14H12ClFN3O4 (M+H)+: m/z=340.

1. temperaturecooled to rt overnight
2. customThe reaction was quenched with a 1 N HCl solution
3. extractionthe aqueous solution was extracted with ethyl acetate
4. washThe combined organic solutions were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrate under reduced pressure
8. customThe residue was purified with flash chromatography (30% ethyl acetate/hexane)

ORD record

ord-8c2e964b6b0e4a549235dcf23289f188

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450351B2