[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([CH3:19])[C:12]([CH3:18])=[C:13]([CH:17]=2)[C:14]([OH:16])=O)[CH:5]=[CH:6][C:7]=1[F:8].C(Cl)(C(Cl)=O)=O.CN(C=O)C.[NH2:31][C:32]1[C:33]([F:40])=[C:34]([OH:39])[CH:35]=[CH:36][C:37]=1[F:38].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.O>[F:40][C:33]1[C:34]([OH:39])=[CH:35][CH:36]=[C:37]([F:38])[C:32]=1[NH:31][C:14](=[O:16])[C:13]1[CH:17]=[C:9]([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)[CH:10]=[C:11]([CH3:19])[C:12]=1[CH3:18]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%).
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