反应详情

To a solution of tert-butyl 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzoate (95 g, 0.16 mmol) in CH2Cl2 (500 mL) at 0° C. was added TFA (500 mL) and then was stirred at room temperature. After 3 h, the reaction mixture was evaporated and the residue was diluted with CH2Cl2 (1.5 L), washed with water (600 mL×2). To the organic layers more water (600 mL) was added, it was neutralized with slow addition of aq. NaHCO3 solution and organic layer was separated. Water (600 mL) was added to the organic layer and adjusted aqueous layer to pH 3-4 with 1N HCl. The organic layer was separated, dried over MgSO4, filtered and concentrated under reduced pressure to give a residue. Toluene (600 mL) was added to the residue and the solution was evaporated and same process was repeated one more time to give the title compound as a white solid (88 g, quant). 1H NMR (400 MHz, CDCl3) δ 7.55 (s, 1H), 7.46-7.49 (d, 2H), 7.16-7.19 (m, 1H), 6.92-6.97 (t, 2H), 6.69-6.71 (t, 2H), 6.62 (s, 1H), 6.49-6.51 (d, 1H), 3.84 (s, 3H), 3.53 (s, 2H), 1.58 (s, 6H); MS (EI) m/z 547 (MH+).

1. customthe reaction mixture was evaporated
2. additionthe residue was diluted with CH2Cl2 (1.5 L)
3. washwashed with water (600 mL×2)
4. additionTo the organic layers more water (600 mL) was added
5. additionit was neutralized with slow addition of aq. NaHCO3 solution and organic layer
6. customwas separated
7. additionWater (600 mL) was added to the organic layer and adjusted aqueous layer to pH 3-4 with 1N HCl
8. customThe organic layer was separated
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto give a residue
13. customthe solution was evaporated