Sodium hydride → HCID 58934836, compound

Participants

Reaction Conditions

Reaction Steps

To the mixture of ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (6 g, 18.5 mmol) and 2-(methylsulfonyl)ethanol (3.45 g, 27.7 mmol) in 125 mL of anhydrous DMF at 0° C. was added sodium hydride (60%, 2.22 g, 55.5 mmol) slowly. After stirring at 0° C. for 45 min, LCMS indicated that majority of starting material was gone. The reaction was warmed to room temperature, and stirred for another 20 min. The reaction was dumped into a dilute hydrochloric acid/ice mixture with vigorously stirring. The product was then extracted with EtOAc. The resulting organic phase was washed with brine, dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on silica gel column with 1:1 EtOAc/hexane containing 1% HOAc. The desired product was obtained as a green yellowish solid, 1.0 g (16.7%). M.P.=118.0-125.0° C. 1H NMR(CDCl3/400 MHz) 7.61(s, 1H), 7.18(s, 1H), 6.66(s, 1H), 5.65(q, 1H, J=6.8 Hz), 4.30(m, 2H), 1.33(t, 3H, J=7.2 Hz). 13C NMR(CDCl3/400 MHz) 164.1, 155.2, 153.8, 136.0, 129.3, 123.5(q, J=287.7 Hz), 115.1, 114.1, 113.6, 104.5, 71 .0(q, J=33.2 Hz), 61.7, 14.4. 19F NMR(CDCl3/400 MHz) −78.9(d, J=6.8 Hz). LC-MS (ES+) 323.7 (M+H, 80%), 295.2(M−27, 100%). HRMS (EI+) m/z calcd for (C13H10ClF3O4) 322.0220, found 322.0231.

Provenance & Evidence