Cyclobutanone → 1-(4-Bromo-3-methoxyphenyl)cyclobutanol

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To a solution of 2-bromo-5-iodoanisole (400 mg, 1.28 mmol) in tetrahydrofuran (5 mL) at −78° C. was added n-butyl lithium (2.5M in hexane, 0.62 mL, 1.55 mmol) dropwise over 15 minutes. The reaction mixture was stirred at −78° C. for 30 minutes, then treated with neat cyclobutanone (0.1 mL, 1.3 mmol) dropwise over 10 minutes and stirred at −78° C. for an additional 1.5 hours. The reaction was quenched with saturated aqueous ammonium chloride solution, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford a yellow oil, which was purified by flash chromatography (12 g silica, 0-50% ethyl acetate/heptane, 27 column volumes). Product fractions were combined and concentrated in vacuo to afford the title compound as a pale yellow oil (40 mg, 12% yield). GCMS 256/258 (M)+; 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J=8.29 Hz, 1H), 7.09 (d, J=1.95 Hz, 1H), 6.98 (dd, J=8.17, 1.83 Hz, 1H), 3.94 (s, 3H), 2.51-2.61 (m, 2H), 2.35-2.46 (m, 2H), 2.02-2.10 (m, 1H), 1.66-1.79 (m, 1H).

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