Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[F:9].[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[Cl-].[NH4+]>C1COCC1>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20]([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[F:9])([OH:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]1-Bromo-2,4-difluoro-benzene (0.67 g, 3.5 mmol) was dissolved in THF (5 mL) and cooled to 0° C. Isopropylmagnesium chloride lithium chloride complex in THF (1.3 M, 2.5 mL, 3.2 mmol) was added. The mixture was stirred for 0.5 hours then added dropwise to a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 2.5 mmol) in THF (10 mL) that had been cooled to −78° C. The mixture was allowed to warm to room temperature then cooled to −78° C. and a solution of saturated aqueous ammonium chloride was added and the mixture extracted into ethyl acetate, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by flash chromatography on silica eluting with 0-50% ethyl acetate/hexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.7 g) as a clear, colourless oil. LCMS m/z 314.3 [M+H]+. R.T.=4.65 min (Analytical Method 4).
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