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

Temperature

-78 °C

A solution of ethyl isobutyrate (11.03 g, 95 mmol) in tetrahydrofuran (75 mL) was added dropwise to a mixture of a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, 100 mL, 100 mmol) and tetrahydrofuran (100 mL) at −78° C. over 15 minutes. The resulting solution was stirred at −78° C. for 45 minutes, and then treated with a solution of 1-bromomethyl-4-fluorobenzene (11.5 mL, 92 mmol) in tetrahydrofuran (25 mL) over 5 minutes. The cooling bath was removed, and the reaction mixture was stirred for 18 hours at room temperature. 1.0 N aqueous hydrochloric acid was added, and the layers were separated. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed with 1.0 N aqueous hydrochloric acid, dried over sodium sulfate, and concentrated under vacuum to provide a brown liquid (20.7 g, quantitative) used without further purification. 1H NMR (300 MHz, CDCl3) δ7.07 (m, 2H), 6.94 (t, J=9 Hz, 2H), 4.10 (q, J=7 Hz, 2H), 2.82 (s, 2H), 1.23 (t, J=7 Hz, 3H), 1.16 (s, 6H).

1. customThe cooling bath was removed
2. stirringthe reaction mixture was stirred for 18 hours at room temperature
3. addition1.0 N aqueous hydrochloric acid was added
4. customthe layers were separated
5. extractionThe aqueous phase was extracted with ethyl acetate
6. washthe combined organic phases were washed with 1.0 N aqueous hydrochloric acid
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under vacuum
9. customto provide a brown liquid (20.7 g, quantitative)
10. customused without further purification

ORD record

ord-090de20b0abe4952bfef246bae56ef04

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06919356B2