反应详情

To a solution of (methoxymethyl)(triphenyl)phosphonium chloride (23.0 g, 66.0 mmol) in toluene (183 mL) was added sodium tert-butoxide (6.60 g, 0.066 mol) at rt under an atmosphere of nitrogen. After stirring for 30 min, a solution of N-(3-chloro-4-fluorophenyl)-4-formyl-1,2,5-oxadiazole-3-carboxamide (7.6 g, 28 mmol) in THF (18 mL) was cannulated into reaction flask. The resulting solution was stirred at rt for 1 h. The reaction was quenched with 1 N HCl and diluted with ethyl acetate and the aqueous layer was extracted with ethyl acetate once. The combined organic solutions were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography (20% ethyl acetate/Hex) to give product (2.0 g 24%, E isomer, 2.6 g, 31%, Z isomer) as white solids. Z isomer: 1H NMR (400 MHz, CDCl3): δ□ 8.54 (s, 1 H) 7.87 (dd, J=6.4, 2.7 Hz, 1 H), 7.42 (m, 1 H), 7.16 (t, J=8.5 Hz, 1 H), 6.66 (d, J=6.6 Hz, 1 H), 6.03 (d, J=6.6 Hz, 1 H), 3.97 (s, 3 H). MF=C12H10ClFN3O3; LCMS for C12H10ClFN3O3(M+H)+: m/z=298.0.

1. stirringThe resulting solution was stirred at rt for 1 h
2. customThe reaction was quenched with 1 N HCl
3. additiondiluted with ethyl acetate
4. extractionthe aqueous layer was extracted with ethyl acetate once
5. washThe combined organic solutions were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified with silica gel chromatography (20% ethyl acetate/Hex)
10. customto give product (2.0 g 24%, E isomer, 2.6 g, 31%, Z isomer) as white solids