反应详情

温度

80 °C

SOCl2 (8.41 mL, 115 mmol) was added to a suspension of 3-bromo-4-hydroxybenzoic acid (5 g, 23.04 mmol) in toluene (50 mL) and the RM was stirred at 80° C. for 2.5 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (25 mL). DIPEA (8.05 mL, 46.1 mmol) was added and the RM was cooled to 0° C., treated with a solution of 4-trifluoromethoxyaniline (3.40 mL, 25.3 mmol) in THF (5 mL) and stirred for 1 h. The RM was treated with 4M NaOH (23.04 mL, 92 mmol), heated at 100° C. for 3 h and the solvent was evaporated off under reduced pressure. The residue was treated with aq. HCl (50 mL of 1M), and extracted with TBME/EtOAc (1:1). The combined extracts were washed with sat. aq. NaHCO3 and brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the crude product was purified by flash chromatography (Silica gel column, 100 g, DCM/EtOAc from 0% to 20EtOAc) and crystallized from cyclohexane/DCM to afford the title compound as a beige solid. UPLC-MS (Condition 1) tR=2.70 min, m/z=375.9/377.8 [M+H]+, m/z=374.0/375.9 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.05 (d, J=8.6 Hz, 1H) 7.35 (d, J=8.6 Hz, 2H) 7.80-7.90 (m, 3H) 8.17 (d, J=2.2 Hz, 1H) 10.26 (s, 1H) 11.03 (s, 1H).

1. customThe solvent was evaporated off under reduced pressure
2. dissolutionthe residue was dissolved in THF (25 mL)
3. temperaturethe RM was cooled to 0° C.
4. stirringstirred for 1 h
5. temperatureheated at 100° C. for 3 h
6. customthe solvent was evaporated off under reduced pressure
7. additionThe residue was treated with aq. HCl (50 mL of 1M)
8. extractionextracted with TBME/EtOAc (1:1)
9. washThe combined extracts were washed with sat. aq. NaHCO3 and brine
10. dry with materialdried over MgSO4
11. customthe solvent was evaporated off under reduced pressure
12. customto give the crude product
13. customwas purified by flash chromatography (Silica gel column, 100 g, DCM/EtOAc from 0% to 20EtOAc)
14. customcrystallized from cyclohexane/DCM