反应详情

温度

60 °C

To a solution of methyl 3-hydroxycyclobutanecarboxylate (1.2 g, 9.0 mmol) in DMF (20 mL) was added sodium hydride (60% wt in mineral oil) (1.8 g, 45 mmol) at RT. The mixture was stirred for 1 h and then 2,5-difluoro-3-(tetrahydro-pyran-4-yl)-pyridine (1.8 g, 9.0 mmol) was added. The reaction mixture was heated to 60° C. for 3 h and then quenched with saturated NH4Cl. The solution was diluted with EtOAc and water and extracted with EtOAc (2×10 mL). The organic extracts were combined, washed with brine (10 mL), dried over MgSO4, filtered, and concentrated to get a residue, which was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) to give the product (3.2 g) as yellow oil.

1. customquenched with saturated NH4Cl
2. additionThe solution was diluted with EtOAc and water
3. extractionextracted with EtOAc (2×10 mL)
4. washwashed with brine (10 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto get a residue, which
9. customwas purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes)