反应详情

温度

75 °C

To a stirred solution of (R)-1-(4-bromophenyl)-2,2,2-trifluoroethanol (2, 69 g, 0.27 mol, >99% ee), 3-methoxy phenylboronic acid (Matrix, 51 g, 0.34 mol, 97% purity), and bis(triphenylphosphine)palladium(II) dichloride (0.95 g, 0.5% mol) in ethanol (560 ml) was added a solution of potassium carbonate (112 g, 0.81 mol) in water (140 ml) under nitrogen. The resulting mixture was heated at 75° C. for 1 h and deemed complete by GC-MS or TLC. After reaction mixture was cooled to 40° C., it was filtered through a pad of Celite, washed with methanol (3×100 ml). The filtrate was diluted with 100 ml of water and concentrated. The resulting syrup was dissolved in 700 ml of ethyl acetate and washed with 1 N sodium hydroxide (2×100 ml), water (2×100 ml) and brine (1×100 ml). The organic layer was heated with activated carbon (14 g) and Hyflo Super Cel (14 g) at 60° C. for 1 h. This mixture was filtered hot and washed with ethyl acetate (100 ml) and then concentrated to a syrup. This syrup was immediately dissolved in 1% ethyl acetate/heptane (700 ml) and stirred for 4 h. The resulting slurry was filtered and dried to give the titled compound as a white crystalline solid (3, 68 g, 89% yield, >99% ee)

1. customAfter reaction mixture
2. temperaturewas cooled to 40° C.
3. filtrationit was filtered through a pad of Celite
4. washwashed with methanol (3×100 ml)
5. additionThe filtrate was diluted with 100 ml of water
6. concentrationconcentrated
7. dissolutionThe resulting syrup was dissolved in 700 ml of ethyl acetate
8. washwashed with 1 N sodium hydroxide (2×100 ml), water (2×100 ml) and brine (1×100 ml)
9. temperatureThe organic layer was heated with activated carbon (14 g) and Hyflo Super Cel (14 g) at 60° C. for 1 h
10. filtrationThis mixture was filtered hot
11. washwashed with ethyl acetate (100 ml)
12. concentrationconcentrated to a syrup
13. dissolutionThis syrup was immediately dissolved in 1% ethyl acetate/heptane (700 ml)
14. filtrationThe resulting slurry was filtered
15. customdried