Br[C:2]1[CH:3]=[CH:4][C:5]([F:29])=[C:6]([C@:8]2([CH2:27][F:28])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:9]2)[CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[C:72](=O)([O-:74])[O-:73].[K+].[K+].O>CN(C=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:19]([NH:18][C:10]1[O:11][C@H:12]([C:14]([F:16])([F:17])[F:15])[CH2:13][C@:8]([C:6]2[CH:7]=[C:2]([CH:3]=[CH:4][C:5]=2[F:29])[C:72]([OH:74])=[O:73])([CH2:27][F:28])[N:9]=1)(=[O:26])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1To a mixture of N-((4S,6S)-4-(5-bromo-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (2.19 g, 4.59 mmol), bis(tri-t-butylphosphine)palladium(0) (0.23 g, 0.46 mmol), xantphos (0.53 g, 0.92 mmol), potassium carbonate (1.90 g, 13.76 mmol) in DMF (15 mL) and water (0.83 ml, 45.9 mmol) was bubbled CO gas for 10 min. The mixture was heated at 90° C. for 4 h, then was allowed to cool to rt. 1N HCl was added until pH˜4. Water was then added and a precipitate was formed. The solid was filtered, washed with water, and dried. The filtrate was concentrated in vacuo. The crude product was purified by silica gel chromatographed, eluting with a gradient of 1% to 8% MeOH in 0.5% AcOH/DCM, to provide the acid as a white solid (0.44 g, 21.45% yield). MS m/z=443 [M+H]+. Calculated for C20H15F5N2O4: 442.3.
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