Oxalyl chloride → N-(2-chloro-6-fluoro-3-hydroxy-phenyl)-2-fluoro-5-(3-fluorophenyl)benzamide

To a solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (478 mg, 2.04 mmol, 1.1 eq) in DCM (9 mL) and DMF (3 drops) at 0° C. was added (COCl)2 (779 mg, 6.14 mmol, 3.3 eq) dropwise. The reaction mixture was stirred at room temperature for 1.5 h, then the solvent removed in vacuo. The residue obtained was dissolved in THF (7 mL) and added dropwise to a mixture of 3-amino-2-chloro-4-fluoro-phenol (intermediate X(f)) (300 mg, 1.86 mmol, 1.0 eq) and NaHCO3 (781 mg, 9.3 mmol, 5.0 eq) in THF (7 mL) at 0° C. After addition was completed, the reaction mixture was warmed to room temperature and stirred overnight. Water was added and the aqueous mixture was extracted with EtOAc. The organic extract was washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 3:20 to 1:4) to give the title as a yellow solid compound (180 mg, 26%).

1. customthe solvent removed in vacuo
2. customThe residue obtained
3. additionAfter addition
4. temperaturethe reaction mixture was warmed to room temperature
5. stirringstirred overnight
6. extractionthe aqueous mixture was extracted with EtOAc
7. extractionThe organic extract
8. washwas washed with 5% Na2CO3, water and brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. customevaporated in vacuo
12. custompurified by column chromatography (EtOAc:petroleum ether, 3:20 to 1:4)

ORD record

ord-d1d783cf3af84ec08b621292584869a7

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249085B2