Potassium Carbonate → 7-(4-propylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To the mixture of ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (0.29 g, 1.0 mmol) and potassium carbonate (0.21g, 1.4 mmol) was added 4-propylphenol (0.153 mL, 1.1 mmol) and 3 mL of dry DMF. The resulting mixture was heated at 110° C. for 15 hrs. LC-MS indicated that the reaction was done. To the reaction was added 15 mL of EtOAc. The resulting organic phase was washed with brine, and the volatiles were removed. To the residue was added 3 mL of THF, and a solution of lithium hydroxide hydrate (105 mg, 2.5 mmol) in 3 mL of water. Then to the resulting mixture was added 3 mL of ethanol. The resulting solution was heated at 80° C. for 5 hrs. LC-MS indicated that the reaction was completed. The volatiles were removed, the residue was diluted with water, and acidified at 0° C. with dilute HCl to pH=1.0, the product was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. After removing the volatiles, it gave a light yellow oil. The residue was purified on reverse phase HPLC. The product was obtained as a light yellow solid, 80 mg (21%). M.P.=143.5-146.5° C. 1H(CDCl3/300 Mhz) 7.80(s, 1H), 7.18-7.13(m, 3H), 6.96(d, J=8.4 Hz, 2H), 6.59-6.52(m, 2H), 5.62(q, 1H, J=6.9 Hz), 2.57(t, 2H, J=6.9 Hz,), 1.67-1.57(m, 2H), 0.93(t, J=7.2 Hz, 3H). 13C NMR(CDCl3/300 MHz)169.5, 163.6, 155.5, 153.0, 139.7(d, J=13.0 Hz), 131.4, 130.2(d, J=5.3 Hz), 123.7(q, J=287.6 Hz), 120.6, 119.8, 113.7, 112.8, 112.0, 105.0, 70.7(q, J=33.5 Hz), 73.6, 24.9, 14.1. 19F(CDCl3/300 MHz) −78.96(d, J=6.9 Hz). LC-MS(EI+) 379.1 (M+1, 100). HRMS (EI+) m/z calcd for (C20H17F3O4) 378.1079(M+), found 378.1061.

Provenance & Evidence