反应详情

3-(4′,5′-Difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester (0.76 g, 1.9 mmol) was dissolved in THF (10 mL) and lithium hydroxide solution (0.5N, 8 mL) was added followed by addition of methanol (2 mL). The mixture was refluxed for 2 hrs and solvents were evaporated. The mixture was extracted with ether and water. The aqueous layer was treated with hydrochloric acid (1N, 5 mL) and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. Solvents were evaporated to give a white solid as 3-(4′,5′-difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid (0.7 g, 96%). HRMS-ES calculated for C21, H15, F3, O4, 411.0814; found m/z 411.0815 [M+Na]+; 1H-NMR (DMSO-d6) δ ppm 13.15 (br, s, 1H), 8.16 (dd, J=7.2, 1.8 Hz, 1H), 7.96-8.04 (m, 1H), 7.32-7.45 (m, 4H), 7.24 (dd, J=13.0, 6.9 Hz, 1H), 7.08 (d, J=8.5 Hz, 2H), 5.24 (s, 2H), 3.76 (s, 3H).

1. temperatureThe mixture was refluxed for 2 hrs
2. customsolvents were evaporated
3. extractionThe mixture was extracted with ether and water
4. additionThe aqueous layer was treated with hydrochloric acid (1N, 5 mL)
5. extractionextracted with ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over sodium sulfate
8. customSolvents were evaporated