Oxalyl chloride → N-(2,6-Difluoro-3-hydroxy-phenyl)-2, 3-dimethyl-5-phenyl-benzamide

To a solution of 2,3-dimethyl-5-phenyl-benzoic acid (315 mg, 1.4 mmol, 1.1 eq) in CH2Cl2 (10 mL) was added oxalyl chloride (530 mg, 4.2 mmol, 3.3 eq) at 0° C. The reaction was allowed to warm to room temperature and stirred for 1 h. The solvent and excess reagent were removed under reduced pressure and the residue that remained dissolved in THF (10 mL) and added dropwise to a mixture of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (184 mg, 1.3 mmol, 1.0 eq) and NaHCO3 (532 mg, 6.3 mmol, 5.0 eq) in THF (8 mL) at 0° C. The reaction was stirred at room temperature for 2 h, water was added and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue was purified by column chromatography (petroleum ether:EtOAc, 20:1 to 10:1, then CH2Cl2:MeOH, 500:1 to 100:1) to give the title compound as a yellow solid (220 mg, 49%).

1. customThe solvent and excess reagent were removed under reduced pressure
2. dissolutionthe residue that remained dissolved in THF (10 mL)
3. stirringThe reaction was stirred at room temperature for 2 h
4. extractionthe aqueous layer was extracted with EtOAc
5. washThe combined organic extracts were washed with water and brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe residue was purified by column chromatography (petroleum ether

ORD record

ord-4d814c142c5b4b698222a32fe3be6db5

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249085B2