反应详情

温度

80 °C

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amine (1.06 g) is dissolved in dimethylsulfoxide (5 ml), and the mixture is degassed and thereto are added [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride (61 mg), potassium acetate (442 mg) and bis(pinacolato)diboron (571 mg). The mixture is degassed and heated to 80° C. under nitrogen flow and stirred for 45 minutes. The reaction solution is allowed to cool to room temperature, and thereto is added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed twice with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (5 ml), and thereto is added dropwise a 30% aqueous hydrogen peroxide solution (1.5 ml) under ice-cooling and stirred at the same temperature for 1 hour and a half. To the reaction mixture is added dropwise saturated aqueous sodium thiosulfate solution under ice-cooling, and thereto is added a saturated brine, and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:1→3:1) to give 2-[(3,5-bis-trifluoromethyl-benzyl)-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-ol (866 mg). MS (m/z): 644 [M+H]+

1. customthe mixture is degassed
2. additionare added [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride (61 mg), potassium acetate (442 mg) and bis(pinacolato)diboron (571 mg)
3. customThe mixture is degassed
4. temperatureto cool to room temperature
5. additionis added a saturated brine
6. extractionthe mixture is extracted with ethyl acetate
7. washThe organic layer is washed twice with a saturated brine
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated under reduced pressure
10. dissolutionThe resulting residue is dissolved in tetrahydrofuran (5 ml)
11. additionis added dropwise a 30% aqueous hydrogen peroxide solution (1.5 ml) under ice-
12. temperaturecooling
13. stirringstirred at the same temperature for 1 hour
14. additionTo the reaction mixture is added dropwise saturated aqueous sodium thiosulfate solution under ice-
15. temperaturecooling
16. additionis added a saturated brine
17. extractionthe mixture is extracted with ethyl acetate
18. washThe organic layer is washed with a saturated brine
19. dry with materialdried over magnesium sulfate
20. concentrationconcentrated under reduced pressure
21. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=4:1→3:1)