[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH:13]([C:15]([O:17]C)=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])[CH:5]=[CH:6][C:7]=1[F:8].[Br-].[Li+]>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])[CH:5]=[CH:6][C:7]=1[F:8]Dimethyl 2-(3,4-difluorophenyl)piperidine-1,4-dicarboxylate (6.578 g, 21.00 mmol) was dissolved in THF (40 mL) and water (0.800 mL). Lithium bromide (14.59 g, 167.97 mmol) and TEA (11.71 mL, 83.98 mmol) were added and the reaction was stirred at 80° C. for 3 h. The reaction mixture was cooled to room temperature and some solvent evaporated in vacuo. EtOAc (150 mL) and water (150 mL) were added, shaken and the phases separated. The organic phase was extracted with water (150 mL). The combined aqueous phases were acidified with 3 M HCl to pH 1 and extracted with EtOAc (2×300 mL). The combined organic phases were dried with Na2SO4, filtered and evaporated in vacuo to yield 2-(3,4-difluorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (5.66 g, 90%) as a light brown oil. MS m/z 298 (M+H)+.
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