1. Preparation of the intermediate 1-(4-bromophenyl)cyclobutanecarboxylic acid methyl ester (1AH-1): Sodium hydride (3.5 g, 88 mmol) was suspended in dimethylformamide (250 mL) under argon protection. The suspension was heated to 35 °C and a solution of methyl 2-(4-bromophenyl)acetate (10 g, 44 mmol) in dimethylformamide (100 mL) was slowly added dropwise over a period of 1 h. Subsequently, stirring was continued at 30 °C for 1 h. The solution of methyl 2-(4-bromophenyl)acetate (10 g, 44 mmol) was added dropwise over a period of 1 h. The solution was then stirred for 1 h at 30 °C.
2. A solution of dimethylformamide (50 mL) of 1,3-dibromopropane (4.4 mL, 44 mmol) was added dropwise to the above reaction mixture over a period of 1 h. The reaction mixture was then stirred overnight at room temperature. The reaction was not complete.
3. In another vessel, sodium hydride (3.5 g, 88 mmol) was suspended in dimethylformamide (100 mL) at 35 °C and this suspension was added dropwise to the reaction mixture over 1 hour. The reaction mixture was again stirred at room temperature overnight.
4. Upon completion of the reaction, the reaction was quenched by careful addition of saturated aqueous ammonium chloride solution (200 mL), followed by dilution with water (500 mL). The product was extracted with ethyl acetate (2 x 500 mL) and the organic phase was washed sequentially with water (3 x 500 mL) and brine (2 x 500 mL).
5. Combine the organic phases, dry with magnesium sulfate, filter and concentrate under reduced pressure. The crude product was purified by fast column chromatography (eluent: 12.5% ethyl acetate in heptane) to afford methyl 1-(4-bromophenyl)cyclobutanecarboxylate (900 mg, 3.3 mmol, 7.5% yield). 6. The structure of the product was determined by 1H NMR.
6. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.45 (d, 2H), 7.15 (d, 2H), 3.65 (s, 3H), 2.80 (m, 2H), 2.45 (m, 2H), 2.05 (m, 1H), 1.85 (m, 1H).
