CO[C:3](=[O:19])[CH2:4][CH:5]1[CH2:8][N:7]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[CH2:6]1.Cl.C[NH:22][O:23][CH3:24].C([Mg]Cl)(C)C.[Cl-].[NH4+].[O:32]1CCC[CH2:33]1>>[F:18][C:12]1[CH:13]=[C:14]([F:17])[CH:15]=[CH:16][C:11]=1[CH2:10][CH2:9][N:7]1[CH2:6][CH:5]([CH2:4][C:3]([N:22]([O:32][CH3:33])[O:23][CH3:24])=[O:19])[CH2:8]1A slurry of methyl{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}acetate (Step 1, 0.5 g, 1.86 mmol) and N,O-dimethylhydroxylamine hydrochloride (272 mg, 2.79 mmol) in tetrahydrofuran (4 mL) was cooled to −20° C. under nitrogen. Isopropylmagnesium chloride (2M in tetrahydrofuran, 2.79 mL, 5.57 mmol) was added dropwise, maintaining the internal temperature between −20 and −5° C. The reaction was stirred at −20° C. for 30 minutes then at room temperature for 2.5 hours. Saturated ammonium chloride solution was added and the mixture stirred vigorously for 5 minutes then extracted with ethyl acetate (x3). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 7% methanol/dichloromethane, to give 2-{1-[2-(2,4-difluorophenyl)ethyl]azetidin-3-yl}-N,N-dimethoxyacetamide (297 mg, 54%). 1H NMR (400 MHz, CDCl3) δ 7.16–7.10 (1H, m), 6.79–6.71 (2H, m), 3.67 (3H, s), 3.51–3.47 (2H, m), 3.14 (3H, s), 2.89–2.79 (3H, m), 2.71 (2H, d, J=6.8 Hz), 2.62 (4H, s); m/z (ES+) 299 (M+H)+.
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