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

HRID 1771612Notes

Reaction equation

[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:9][C:8]([O:18][CH3:19])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[C:28]([F:35])=[C:29]([OH:34])[CH:30]=[CH:31][C:32]=1[F:33].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:35][C:28]1[C:29]([OH:34])=[CH:30][CH:31]=[C:32]([F:33])[C:27]=1[NH:26][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([O:18][CH3:19])[CH:9]=[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[C:2]=1[F:1]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-fluoro-3-(3-fluorophenyl)-5-methoxybenzoic acid (402 mg, 1.52 mmol, 1.1 eq) in CH2Cl2 (20 mL) at 0° C. was added oxalylchloride (525 mg, 4.14 mmol, 3.0 eq) and DMF (5 drops). The solution was stirred at 0° C. for 2 h then the solvent removed in vacuo. The residue was taken up in THF (10 mL) and added dropwise to a mixture of 3-amino-2,4-difluorophenol (intermediate X(a)) (200 mg, 1.38 mmol, 1.0 eq) and NaHCO3 (348 mg, 4.14 mmol, 3.0 eq) in THF (10 mL) at 0° C. The mixture was stirred at 0° C. for 4 h then poured into water and extracted with EtOAc. The organic extract was washed with water, brine, dried (Na2SO4) filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a white solid (300 mg, 50%).

Workup

customthe solvent removed in vacuo
stirringThe mixture was stirred at 0° C. for 4 h
extractionextracted with EtOAc
extractionThe organic extract
washwas washed with water, brine
dry with materialdried (Na2SO4)
filtrationfiltered
customevaporated in vacuo
customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

Sources & evidence

ORD record: ord-e819554d1aaf4e3b888388a5f24c2f44
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249085B2

Reaction notes

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