反应详情

A solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (1.6 g, 7 mmol, 3.0 eq) in SOCl2 (20 mL) was heated at reflux for 3 h. The excess thionyl chloride was removed in vacuo and the residue obtained dissolved in THF (10 mL) and added dropwise to a solution of 2,6-dichloro-3-methoxy-aniline (450 mg, 2.3 mmol, 1.0 eq) and NaH (85 mg, 3.4 mmol, 1.5 eq) in THF (10 mL). The reaction was stirred at room temperature for 2 h then quenched by addition of aqueous NH4Cl. The mixture was extracted with EtOAc and the combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound (200 mg, 21%).

1. temperatureat reflux for 3 h
2. customThe excess thionyl chloride was removed in vacuo
3. customthe residue obtained
4. customthen quenched by addition of aqueous NH4Cl
5. extractionThe mixture was extracted with EtOAc
6. dry with materialthe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe residue obtained
10. customwas purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4)