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

Temperatur

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, 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.

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-Eintrag

ord-429a24a5c583444b98e7c74891419169

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08951536B2