反应详情

To a solution of 3-(3-fluorophenyl)-5-methyl-benzoic acid (448 mg, 1.95 mmol, 1.1 eq) in CH2Cl2 (10 mL) was added (COCl)2 (742 mg, 5.85 mmol, 3.3 eq) and DMF (3 drops) at 0° C. The reaction mixture was stirred at room temperature for 1.5 h. The resulting mixture was concentrated in vacuo to remove the solvent and excess reagent. The solid obtained was dissolved in THF (10 mL) and added dropwise to a mixture of 3-amino-4-fluoro-2-methylphenol (intermediate X(e)) (250 mg, 1.77 mmol, 1.0 eq) and NaHCO3 (744 mg, 8.86 mmol, 5.0 eq) in THF (15 mL) at 0° C. The reaction was allowed to warm to room temperature and stirred 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 obtained was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (396 mg, 63%).

1. concentrationThe resulting mixture was concentrated in vacuo
2. customto remove the solvent and excess reagent
3. customThe solid obtained
4. temperatureto warm to room temperature
5. stirringstirred 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 obtained
13. customwas purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1)