[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:19][C:20]1[C:21]([F:31])=[C:22]([F:30])[C:23](F)=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26]>C1COCC1>[Br:19][C:20]1[C:21]([F:31])=[C:22]([F:30])[C:23]([NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[F:1])=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26]To a solution of 2-fluoroaniline (4.27 ml, 44.3 mmol) in THF (30 ml) at −78° C. was added LiHMDS (66.6 ml, 1 M in THF, 66.6 mmol) dropwise. The reaction mixture was stirred for 10 min and a solution of 5-bromo-2,3,4-trifluorobenzoic acid (5.63 g, 22.2 mmol) in THF (40 ml) was added to the mixture. The reaction was slowly warmed to room temperature and stirred at this temperature for 4 h. The mixture was concentrated, quenched with 10% HCl solution (70 ml), and extracted with EtOAc (2×200 ml). The combined organic solution was dried over MgSO4 and concentrated to dryness. Purification by trituration with boiling CH2Cl2 gave 4.40 g (57%) of 5-bromo-3,4-difluoro-2-(2-fluorophenylamino)benzoic acid as a yellow solid.
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