Ethyl 2-butynoate → 3-(2-Fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-fluoro-5-methyl-phenol (0.97 mL, 8.91 mmol) and ethyl-2-butynoate (2.0 g, 17.8 mmol) in tetrahydrofuran (13.7 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.33 mL, 8.91 mmol). The reaction was then heated at 130° C. for 4 h. At this time, the reaction was cooled to 25° C. and was stirred at 25° C. overnight. At this time, the reaction was diluted with dichloromethane (100 mL) and was washed with a 2N aqueous hydrochloric acid solution (1×100 mL), a 0.5N aqueous sodium hydroxide solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 2% ethyl acetate/hexanes) afforded 3-(2-fluoro-5-methyl-phenoxy)-but-2-enoic acid ethyl ester (1.12 g, 52%) as a clear oil: HR-ES-MS m/z calculated for C13H15O3F [M+H]+ 239.1078, observed 239.1078; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.12 (t, J=7.0 Hz, 3H), 2.30 (s, 3H), 2.43 (s, 3H), 4.00 (q, J=7.0 Hz, 2H), 4.69 (s, 1H), 7.01-7.19 (m, 2H), 7.30 (dd, J=10.7, 8.3 Hz, 1H).

Provenance & Evidence