Potassium Carbonate → 3-(2-Chloro-4-trifluoromethylphenyl)-4-(4-hydroxybenzyl)-7-methoxychromen-2-one

Temperature

70 °C

A mixture of 2-(chloro-4-trifluoromethylphenyl)-acetic acid (3.2 g, 13.41 mmol) and 1,1′-carbonyldiimidazole (2.72 g, 16.77 mmol) in DMF (15 mL) was heated to 70° C. for 25 min. The reaction mixture was cooled to 10° C. and K2CO3 (2.78 g, 20.1 mmol), 1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)-ethan-1-one (1.73 g, 6.7 mmol, prepared as described in Example 4A), DMAP (164 mg, 1.34 mmol) and DMF (10 mL) were added. After stirring the reaction mixture at 115° C. for 1.5 h, the resulting suspension was cooled to r.t., poured onto AcOEt/H2O and the layers were separated. The organic layer was washed with H2O, aq 1N HCl and brine, was dried (MgSO4) and the solvent was removed in vacuo. The resultant red residue was purified using flash chromatography (silica gel, 2:1 to 1:2 hexanes:Et2O) to provide the title compound as a white solid showing: 1H NMR (300 MHz, CDCl3) δ 7.75 (s, 1H), 7.53 (br d, 1H, J=8.0 Hz), 7.47 (d, 1H, J=9.0 Hz), 7.33 (d, 1H, J=8.0 Hz), 6.92-6.85 (m, 3H), 6.80 (d, 1H, J=2.5, 9.0 Hz), 6.70 (d, 2H), J=8.5 Hz), 4.95-4.64 (very br s, 1H), 4.02 (d, 1H, J=15.5 Hz), 3.88 (s, 3H), 3.76 (d, 1H, J=15.5 Hz). MS (ESI) m/z 461 (M+H)+.

1. temperatureThe reaction mixture was cooled to 10° C.
2. temperaturethe resulting suspension was cooled to r.t.
3. additionpoured onto AcOEt/H2O
4. customthe layers were separated
5. washThe organic layer was washed with H2O, aq 1N HCl and brine
6. dry with materialwas dried (MgSO4)
7. customthe solvent was removed in vacuo
8. customThe resultant red residue was purified

ORD record

ord-8d37307ae9d84965a4f0072a948625c8

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06620838B1