反应详情

温度

80 °C

To a pale yellow solution of 1-(2,4-dichloro-phenyl)-2-(5-ethyl-2H-pyrazol-3-yloxy)-propan-1-one (9.00 g, 28.7 mmol) in 1,2-dichloroethane (125 ml) is slowly added via syringe titanium tetrachloride (3.80 ml, 34.5 mmol) generating a dark red solution. The reaction mixture is heated at 80° C. for 3 hours and allowed to cool to RT. The reaction mixture is poured slowly into NH4Cl (200 ml) and basified (pH 8) using Na2CO3 (200 ml). EtOAc (300 ml) is added and the biphasic solution is filtered through Celite® 521 (filter material) to remove titanium salts. The solution is extracted with EtOAc (3×75 ml) and the combined organics washed with H2O (1×100 ml), and brine (100 ml), dried (Na2SO4), filtered and concentrated in vacuo to yield an amber solid. The residue is crystallized from hot EtOAc/iso-hexane (1:5, 30 ml) to yield white solid: The mother liquor is purified using a Flashmaster (SiO2 150 ml/70 g column) eluting with 3:1 iso-hexane/EtOAc to yield a yellow solid which is crystallized from hot EtOAc/iso-hexane (1:8, 30 ml) to yield the title compound as a pale yellow solid; MS: m/z 295.15 [M+H]+

1. temperatureto cool to RT
2. filtrationthe biphasic solution is filtered through Celite® 521 (filter material)
3. customto remove titanium salts
4. extractionThe solution is extracted with EtOAc (3×75 ml)
5. washthe combined organics washed with H2O (1×100 ml), and brine (100 ml)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto yield an amber solid
10. customThe residue is crystallized from hot EtOAc/iso-hexane (1:5, 30 ml)
11. customto yield white solid
12. customThe mother liquor is purified
13. washeluting with 3:1 iso-hexane/EtOAc
14. customto yield a yellow solid which
15. customis crystallized from hot EtOAc/iso-hexane (1:8, 30 ml)