Ethyl 3-(4-fluorophenyl)-2,2-dimethylpropanoate

459-46-1

97-62-1

676621-95-7

Preparation of ethyl 3-(4-fluorophenyl)-2,2-dimethylpropionate: a solution of ethyl isobutyrate (11.03 g, 95 mmol) in tetrahydrofuran (75 mL) was added dropwise to a mixture of lithium bis(trimethylmethylsilyl)amide in tetrahydrofuran (1.0 M, 100 mL, 100 mmol) and tetrahydrofuran (100 mL) over a period of 15 min at -78 °C. (100 mL). The resulting solution was stirred at -78 °C for 45 min, followed by addition of a solution of 1-bromomethyl-4-fluorobenzene (11.5 mL, 92 mmol) in tetrahydrofuran (25 mL) over 5 min. The cooling bath was removed and the reaction mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the reaction was acidified by adding 1.0 N aqueous hydrochloric acid and partitioned. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed with 1.0 N aqueous hydrochloric acid, dried over anhydrous sodium sulfate, and concentrated in vacuum to afford the brown liquid product ethyl 3-(4-fluorophenyl)-2,2-dimethylpropionate (20.7 g, quantitative yield), which could be used in subsequent steps without further purification. The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3): δ7.07 (m, 2H), 6.94 (t, J=9Hz, 2H), 4.10 (q, J=7Hz, 2H), 2.82 (s, 2H), 1.23 (t, J=7Hz, 3H), 1.16 (s, 6H).