[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([I:10])=[CH:4][C:3]=1[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)C(C)C)(C)C.[C:26]([O:29][CH2:30][C:31](Cl)=[O:32])(=[O:28])[CH3:27]>CN(C=O)C>[C:26]([O:29][CH2:30][C:31]([N:14]1[CH2:13][CH2:12][CH:11]([C:3]2[CH:4]=[C:5]([I:10])[C:6]([O:8][CH3:9])=[CH:7][C:2]=2[F:1])[CH2:16][CH2:15]1)=[O:32])(=[O:28])[CH3:27]A stirred solution of 4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidine (50 mg; 0.149 mmol) in DMF (1.2 mL) under N2 was treated with N,N-diisopropylethylamine (26 μL; 0.149 mmol), followed by acetoxyacetyl chloride (16 μL, 0.149 mmol). The resultant solution was stirred at room temperature for 5 h. The reaction was partitioned between EtOAc (25 mL) and saturated NaHCO3 (25 mL). The aqueous layer was extracted with EtOAc (3×25 mL) and the combined organic fractions were washed with water and brine (25 mL each), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography, eluting with EtOAC/hexanes, to afford 2-[4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetate as a colorless oil. LCMS=435.8 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.52 (d, J=8.2 Hz, 1 H), 6.56 (d, J=12.2 Hz, 1 H), 4.76 (s, 2 H), 4.76-4.70 (m, 1H), 3.85 (s, 3 H), 3.76 (br d, J=13 Hz, 1 H), 3.17 (t, J=12.6 Hz, 1 H), 2.98 (tt, J=12.1, 3.4 Hz, 1 H), 2.68 (t, J=12.4 Hz, 1 H), 2.20 (s, 3 H), 1.90-1.82 (m, 2 H), 1.70-1.62 (m, 2H).
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