[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1.[CH2:12]([O:14][C:15](=[O:19])[C:16]#[C:17][CH3:18])[CH3:13].N12CCCN=C1CCCCC2>O1CCCC1>[CH2:12]([O:14][C:15](=[O:19])[CH:16]=[C:17]([O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=1)[CH3:18])[CH3:13]A mixture of 3-trifluoromethyl-phenol (1.09 mL, 8.96 mmol) and ethyl-2-butynoate (2.0 g, 17.83 mmol) in tetrahydrofuran (14 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.4 mL, 9.37 mmol). The reaction was then heated at 130° C. for 2 h. At this time, the reaction was concentrated in vacuo. The residue dissolved in dichloromethane (100 mL) and was washed with a 2N aqueous hydrochloric acid solution (1×100 mL), a 1N aqueous sodium hydroxide solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organics were then dried over magnesium sulfate, filtered, rinsed with dichloromethane and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 1-10% ethyl acetate/hexanes) afforded 3-(3-trifluoromethyl-phenoxy)-but-2-enoic acid ethyl ester (1.31 g, 53%) as a clear, colorless oil: HR-ES-MS m/z calculated for C13H13O3F3 [M+H]+ 275.0890, observed 275.0889; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13 (t, J=7.1 Hz, 3H), 2.45 (s, 3H), 4.01 (q, J=7.1 Hz, 2H), 4.68 (s, 1H), 7.49 (d, J=7.9 Hz, 1H), 7.57 (br. s., 1H), 7.66-7.75 (m, 2H).
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