反应详情

温度

50 °C

A mixture of ethyl {4-[4-({[5-(hydroxymethyl)isoxazol-3-yl]oxy}methyl)-5-methyl-1,3-oxazol-2-yl]phenyl}acetate (500 mg), 4-[(E)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-ol (389 mg), 1,1′-(azodicarbonyl)dipiperidine (440 mg), tributylphosphine (0.501 mL) and tetrahydrofuran (20 mL) was stirred at 50° C. for 1 hr. After cooling, the resulting precipitate was removed by filtration, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography and eluted with acetone-hexane (1:5-1:4-1:3, v/v). The obtained eluate was subjected to reversed phase HPLC and eluted with acetonitrile-water (10:90-100:0, v/v). The obtained fraction was concentrated, and saturated aqueous sodium hydrogen carbonate was added to the residue. The mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give ethyl (4-{4-[({5-[({4-[(E)-2-(2-ethyl-1,3-thiazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]isoxazol-3-yl}oxy)methyl]-5-methyl-1,3-oxazol-2-yl}phenyl)acetate (257 mg, yield 30%) as pale-yellow amorphous form.

1. temperatureAfter cooling
2. customthe resulting precipitate was removed by filtration
3. concentrationthe filtrate was concentrated
4. washeluted with acetone-hexane (1:5-1:4-1:3
5. washeluted with acetonitrile-water (10:90-100:0
6. concentrationThe obtained fraction was concentrated
7. additionsaturated aqueous sodium hydrogen carbonate was added to the residue
8. extractionThe mixture was extracted with ethyl acetate-tetrahydrofuran
9. washThe organic layer was washed with saturated brine
10. dry with materialdried over anhydrous magnesium sulfate
11. concentrationconcentrated