[NH2:1][C:2]1[CH:11]=[C:10]([F:12])[C:9](Br)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:14][C:15]1[C:19](B2OC(C)(C)C(C)(C)O2)=[C:18]([CH3:29])[O:17][N:16]=1.O.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O>[NH2:1][C:2]1[CH:11]=[C:10]([F:12])[C:9]([C:19]2[C:15]([CH3:14])=[N:16][O:17][C:18]=2[CH3:29])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]To methyl 2-amino-5-bromo-4-fluorobenzoate (20 g, 80.6 mol.) and 3,5-Dimethylisoxazole-4-boronic acid pinacol ester (24.2 g, 108.9 mol., 1.35 mmol) was added to a solvent mixture of 1,2-dimethoxymethane (120 ml) and water (60 ml). To the above mixture were added PEPPSI-Ipr (3120 mg, 4.2 mmol, 0.05 equiv.) and Cs2CO3 (78.8 g, 241 mol., 3 equiv.). The reaction mixture was heated at 120° C. for 2 h in a pressure tube. The reaction mixture was then diluted with EtOAc (100 ml), washed with bring (50 ml×2). The organic solvent was evaporated and the residue was dissolved in DCM and purified with combi-flash column chromatography (product came out at 50% EtOAc/Hexane) to afford methyl 2-amino-5-(3,5-dimethylisoxazol-4-yl)-4-fluorobenzoate.
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