反应详情

温度

0 °C

DIAD (2.45 mL, 12.6 mmol) was slowly added to a solution of 2-((1S,2R)-2-(1-(5-ethoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol (2.45 g, 8.41 mmol), 4-bromo-3,5-difluorophenol (1.93 g, 9.25 mmol), and triphenylphosphine (3.31 g, 12.6 mmol) in DCM (30 mL) that had been cooled to 0° C. The ice bath was removed and the resulting mixture was stirred at rt for 3 hrs. The reaction mixture was diluted with DCM (20 mL) and washed with a 2 N NaOH solution (30 mL×1). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (KP-Sil 100 g SNAP column, Biotage system) eluting with 5-40% EtOAc:hexanes over 12 CV to afford the title compound. LC/MS (m/z): 482 (M+H)+.

1. customThe ice bath was removed
2. additionThe reaction mixture was diluted with DCM (20 mL)
3. washwashed with a 2 N NaOH solution (30 mL×1)
4. dry with materialThe organic phase was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by column chromatography on silica gel (KP-Sil 100 g SNAP column, Biotage system)
8. washeluting with 5-40% EtOAc