Dimethylformamide → N-(2,6-Difluoro-3-hydroxy-phenyl)-5-(3,4-difluorophenyl)-2,3-dimethyl-benzamide

To a solution of 5-(3,4-difluorophenyl)-2,3-dimethyl-benzoic acid (395 mg, 1.51 mmol, 1.1 eq) in CH2Cl2 (5 mL) was added (COCl)2 (521.6 mg, 4.11 mmol, 3.0 eq) dropwise at 0° C. DMF (10 mg, 0.14 mmol, 0.1 eq) was added and the reaction mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure to remove the solvent and excess reagent. The residue obtained was dissolved in THF (4 mL) and added dropwise to a mixture of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (198 mg, 1.37 mmol, 1.0 eq) and NaHCO3 (575 mg, 6.85 mmol, 5.0 eq) in THF (4 mL) at 0° C. After addition was completed the reaction mixture was stirred at room temperature for 30 min. Water was added and the aqueous layer extracted with EtOAc. The combined organic extracts were washed with saturated NaHCO3, water and brinc, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (petroleum ether:EtOAc, 10:1 to 4:1) to give the title compound as a white solid (100 mg, 19%).

1. concentrationThe resulting mixture was concentrated under reduced pressure
2. customto remove the solvent and excess reagent
3. customThe residue obtained
4. additionAfter addition
5. stirringwas stirred at room temperature for 30 min
6. extractionthe aqueous layer extracted with EtOAc
7. washThe combined organic extracts were washed with saturated NaHCO3, water and brinc
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. customThe residue was purified by column chromatography (petroleum ether:EtOAc, 10:1 to 4:1)

ORD record

ord-62727e5711b943d29c9d8aa54cd9f545

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249085B2