Ethyl Acetate → Ethyl 3-(2-Fluoro-4-methoxyphenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

An oven dried flask was charged with sodium hydride (60%) (389 mg, 9.73 mmol) and THF (25 mL) and cooled to 0° C. Triethyl phosphonoacetate (1.948 mL, 9.73 mmol) was added dropwise and the reaction was heated to 50° C. for 1 hr. The reaction was then cooled to 0° C., and 2-fluoro-4-methoxy-benzaldehyde (1000 mg, 6.49 mmol) was added via cannula in THF (4×5 mL). The reaction was then heated at reflux for 16 hours. Next, the reaction was cooled to room temperature and diluted with ethyl acetate (75 mL). The organic layer was washed with water (2×75 mL) and brine (75 mL), dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in ethanol (20 mL) and 10% palladium on carbon (100 mg) was added. The reaction was placed under an atmosphere of H2 (balloon) and stirred for 4 hours. The reaction was then filtered and concentrated. Purification of the residue via flash chromatography on silica gel (0 to 40% ethyl acetate/hexanes) afforded ethyl 3-(2-fluoro-4-methoxyphenyl)propanoate. 1H NMR (CDCl3, 500 MHz) δ 7.09 (t, J=8.5 Hz, 1H), 6.60 (m, 2H), 4.12 (q, J=7.2 Hz, 2H), 3.77 (s, 3H), 2.90 (t, J=7.6 Hz, 2H), 2.58 (t, J=7.7 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).

Provenance & Evidence