[Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1.C([Mg]Cl)(C)C.C(OCC)C.[O:23]1[CH2:26][C:25](=[O:27])[CH2:24]1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:25]2([OH:27])[CH2:26][O:23][CH2:24]2)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1To a solution of 2-chloro-4-iodo-6-(trifluoromethyl)pyridine (1.00 g, 3.25 mmol, European Journal of Organic Chemistry, (18), 3793-3798, 2004) in tetrahydrofuran (20 mL) at 0° C. was added dropwise 2.0 M isopropylmagnesium chloride in diethyl ether (1.95 mL, 3.90 mmol, Aldrich). After stirring for 30 minutes at 0° C., a solution of oxetan-3-one (0.281 g, 3.90 mmol, Synthonix) in Tetrahydrofuran (5 mL) was added. After stirring for 1 hour, the reaction was quenched by the addition of water and ammonium chloride. The product was extracted with two portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-40% EtOAc in hexanes on a 40 g silica gel cartridge afforded purified product (0.31 g, 38%). LCMS (M+H)+: 254.1.
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