反应详情

To a mixture of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (365 mg, 1.56 mmol, 1.1 eq) and (COCl)2 (541 mg, 4.26 mmol, 3.0 eq) in DCM (10 mL) was added DMF (3 drops). The reaction mixture was stirred at room temperature for 2 h, then concentrated in vacuo. The residue obtained was dissolved in THF (5 mL) and added dropwise to a solution of 3-amino-4-fluoro-2-methyl-phenol (200 mg, 1.42 mmol, 1.0 eq) in THF (15 mL) at 0° C. After the addition was completed, the reaction mixture was allowed to warm to room temperature and stirred for 2 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a yellow solid (300 mg, 59%).

1. concentrationconcentrated in vacuo
2. customThe residue obtained
3. additionAfter the addition
4. temperatureto warm to room temperature
5. stirringstirred for 2 h
6. extractionextracted with EtOAc
7. extractionThe organic extract
8. washwas washed with water and brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. customevaporated in vacuo
12. custompurified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)