Ethyl Acetate → ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-hydroxy-4-fluorobenzaldehyde (log, 71.4 mmol), ethyl 4,4,4-trifluorocrotonate (15 mL, 100 mmol), and anhydrous potassium carbonate (14.8 g, 107.1 mmol) in 40 ml dry dimethylformamide was heated to 90° C. for five hours. LC-MS indicated that the reaction was done. After cooling to room temperature, to the reaction was added 500 mL of ethyl acetate. The organic phase was washed with brine (×3), and was then dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on silica gel column with 1:18 EtOAc/hexane. It gave 12.5 g (60%) product as a light yellow oil. 1H NMR (CDCl3/300 MHz) 7.73(s, 1H), 7.30-7.22(m, 1H), 6.79-6.73(m, 2H), 5.76(q, J=6.9 Hz, 1H), 4.38(m, 2H), 1.37(t, J=7.2 Hz, 3H). 13C(CDCl3/300 MH) 167.2, 164.0, 163.9, 155.0(d, J=13.0 Hz), 136.3(d, J=1.28 Hz), 131.0(d, J=10.4 Hz), 123.5(q, J=287.5 Hz), 115.9(dd, J=2.4, 7.3 Hz), 110.2(d, J=22.5 Hz), 104.4(d, J=26.0 Hz), 71.0(q, J=33.2 Hz), 61.7(d, J=10.4 Hz), 14.4. 19F(CDCl3/300 MHz) −79.0(d, J=6.5 Hz), −104.8(m). LC-MS(ES+) 291.0(M+1, 100), HRMS (EI+) m/z calcd for (C13H10F4O3) 290.0566(M+), found 290.0586.

Provenance & Evidence