19936-14-2

1191-95-3

589-87-7

19936-14-2

Preparation of the intermediate 1-(4-bromophenyl)cyclobutanol (10-1): 1-bromo-4-iodobenzene (1.6293 g, 5.75 mmol) was dissolved in anhydrous tetrahydrofuran (10 mL). The reaction system was cooled to -78 °C, n-butyllithium (2.5 M hexane solution, 2.42 mL, 6.05 mmol) was slowly added under nitrogen protection and stirred continuously at -78 °C for 20 min. Subsequently, cyclobutanone (0.448 mL, 6.05 mmol) was added dropwise to the above cold solution. After the dropwise addition, the reaction system was gradually warmed to room temperature and stirring was continued for 16 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution and extracted with a 1:1 (v/v) mixture of ethyl acetate/tetrahydrofuran. The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product as a thick oil. The crude product was purified by silica gel column chromatography using 0% to 30% ethyl acetate/heptane gradient elution to afford the target compound 1-(4-bromophenyl)cyclobutanol (0.8033 g, 65% yield) as a clear oil.