反应详情

温度

70 °C

To a mixture of (4-methyl-pyrimidin-2-yl)-[3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amine (20.0 g, 56.9 mmol), (1S,4R)-4-(5-Bromo-thiazol-2-yl)-4-hydroxy-2,2-dimethyl-cyclohexanecarboxylic acid methyl ester (19.8 g, 56.9 mmol), and PdCl2(dppf)2 (2.33 g, 2.85 mmol) in degassed 2-methyltetrahydrofuran (237 mL), was added sodium carbonate (2 M in H2O, 56.9 mL, 114 mmol). The reaction flask was purged with nitrogen and then heated to 70° C. for 5 hours. The mixture was cooled to room temperature, diluted with ethyl acetate (100 mL) and filtered over celite. The solution was washed with water, dried over MgSO4, filtered and concentrated in vacuo. Purification by chromatography on silica gel (Isco CombiFlash 100:0 to 40:60, hexanes:ethyl acetate), then by Chromatography on silica gel (2:98, methanol:dichloromethane) provided 17.5 g (37.4 mmol 66%) of (1S,4R)-4-hydroxy-2,2-dimethyl-4-{5-[3-methyl-5-(4-methyl-pyrimidin-2-ylamino)-phenyl]-1,3-thiazol-2-yl}-cyclohexanecarboxylic acid methyl ester as a light tan foam.

1. customThe reaction flask was purged with nitrogen
2. temperatureThe mixture was cooled to room temperature
3. additiondiluted with ethyl acetate (100 mL)
4. filtrationfiltered over celite
5. washThe solution was washed with water
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customPurification by chromatography on silica gel (Isco CombiFlash 100:0 to 40:60, hexanes:ethyl acetate)