[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[CH:11]=1)[C:6]([OH:8])=O)#[N:2].[NH2:19][C:20]1[C:21]([F:28])=[C:22]([OH:27])[CH:23]=[CH:24][C:25]=1[F:26].C([O-])(O)=O.[Na+]>O=S(Cl)Cl.C1COCC1>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[CH:11]=1)[C:6]([NH:19][C:20]1[C:25]([F:26])=[CH:24][CH:23]=[C:22]([OH:27])[C:21]=1[F:28])=[O:8])#[N:2]3-Cyano-5-(3-fluorophenyl)benzoic acid (500 mg, 2.1 mmol, 1 eq) was dissolved in SOCl2 (15 mL) and heated at reflux overnight. The excess SOCl2 was 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-difluorophenol (280 mg, 2 mmol, 0.95 eq) and NaHCO3 (880 mg, 10.5 mmol, 5 eq) in THF (40 mL). The reaction was stirred at room temperature for 3 h, then filtered and the filtrate concentrated in vacuo. The residue was purified by column chromatography (petroleum ether: EtOAc, 10:1) to give the title compound as a white solid (500 mg, 64%).
Loading…