反应详情

To a solution of 2-fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid (intermediate III(e)) (597 mg, 2.4 mmol, 1.1 eq) in CH2Cl2 (15 mL) was added (COCl)2 (916 mg, 7.2 mmol, 3.3 eq) and DMF (5 drops). The reaction mixture was stirred at room temperature for 2 h, then the solvent and excess reagent were removed under reduced pressure. The residue obtained was dissolved in THF (20 mL) and added dropwise to a mixture of 3-amino-2,4-dimethylphenol (intermediate X(c)) (300 mg, 2.2 mmol, 1.0 eq) and NaHCO3 (920 mg, 10.9 mmol, 5.0 eq) in THF (20 mL) at 0° C. After the addition was completed, the reaction was allowed to warm to room temperature and stirred for a further 1 h. The reaction was then poured into water and extracted with EtOAc. The combined organic layers were washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue obtained was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (588 mg, 73%).

1. customthe solvent and excess reagent were removed under reduced pressure
2. customThe residue obtained
3. additionAfter the addition
4. temperatureto warm to room temperature
5. stirringstirred for a further 1 h
6. extractionextracted with EtOAc
7. washThe combined organic layers were washed with water and brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. customThe residue obtained
12. customwas purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1)