反应详情

温度

80 °C

Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-carbamate (11.5 g), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium dichloromethane complex (3.51 g), potassium acetate (6.33 g) and bis(pinacolato)diboron (10.9 g) are dissolved in dimethylsulfoxide (75 ml), and the mixture is heated to 80° C. under nitrogen atmosphere and stirred for 30 minutes. The reaction solution is cooled to room temperature and thereto are added water and ethyl acetate, and the insoluble materials are removed by filtration through Celite™, and the mixture is separated and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (100 ml) and thereto is added dropwise a 30% aqueous hydrogen peroxide solution (50 ml) under ice-cooling and the mixture is stirred for 1 hour. Thereto is added a saturated aqueous sodium thiosulfate solution under ice-cooling to consume the excess hydrogen peroxide, followed by an addition of water and ethyl acetate, and the mixture is separated. 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 (chloroform:methanol=1:0→9:1) to give benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-hydroxy-pyrimidin-2-yl)-carbamate (9.70 g). MS (m/z): 472 [M+H]+

1. temperatureThe reaction solution is cooled to room temperature
2. customthe insoluble materials are removed by filtration through Celite™
3. customthe mixture is separated
4. washthe organic layer is washed with a saturated brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe resulting residue is dissolved in tetrahydrofuran (100 ml)
8. additionis added dropwise a 30% aqueous hydrogen peroxide solution (50 ml) under ice-
9. temperaturecooling
10. stirringthe mixture is stirred for 1 hour
11. additionThereto is added a saturated aqueous sodium thiosulfate solution under ice-
12. temperaturecooling
13. customto consume the excess hydrogen peroxide
14. additionfollowed by an addition of water and ethyl acetate
15. customthe mixture is separated
16. washThe organic layer is washed with a saturated brine
17. dry with materialdried over magnesium sulfate
18. concentrationconcentrated under reduced pressure
19. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→9:1)