反应详情

To a solution of 2-fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid (intermediate III(f)) (597 mg, 2.41 mmol, 1.1 eq) in CH2Cl2 (15 mL) and DMF (5 drops) was added (COCl)2 (916 mg, 7.22 mmol, 3.3 eq) at 0° C. The reaction mixture was stirred at room temperature for 1.5 h. The resulting mixture was concentrated under reduced pressure to remove the solvent and excess reagent and the residue obtained dissolved in THF (20 mL) and added dropwise to a solution of 3-amino-2,4-dimethylphenol (intermediate X(c)) (300 mg, 2.18 mmol, 1.0 eq) and NaHCO3 (920 mg, 10.9 mmol, 5 eq) in THF (20 mL) at 0° C. After the addition was completed, the reaction mixture was stirred at room temperature for 1 h. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (270 mg, 34%).

1. concentrationThe resulting mixture was concentrated under reduced pressure
2. customto remove the solvent and excess reagent
3. customthe residue obtained
4. additionAfter the addition
5. stirringthe reaction mixture was stirred at room temperature for 1 h
6. extractionthe aqueous layer extracted 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. customThe residue was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1)