反应详情

To a cooled (0° C.) suspension of NaH (0.084 g. 3.5 mmol) and Kl (0.1 g, 0.6 mmol) in DMF (10 mL) is added dropwise a solution of 6-bromo-1-oxo-1,2,3,4-tetrahydroisoquinoline (0.65 g, 2.9 mmol) in DMF (10 mL). After 15 minutes, a solution of 5-(4-fluorophenyl)-2-(chloromethyl)pyridine (1.27 g, 5.8 mmol) in DMF (10 mL) is added dropwise and the resulting solution stirred for 12 hours. The reaction mixture is then partitioned between water (200 mL) and EtOAc (200 mL). The aqueous layer is extracted with EtOAc (1×200 mL). The combined organic extracts are then washed with H2O (4×200 mL), saturated NaCl solution (2×200 mL), and dried over MgSO4 and concentrated in vacuo. The resulting material is chromatographed (silica gel. 1:4 EtOAc-hexanes) to afford 6-bromo-2-{[5-(4-fluorophenyl)-2-pyridyl]methyl}-1-oxo-1,2,3,4 -tetrahydroisoquinoline as pale yellow oil.

1. temperatureTo a cooled
2. customThe reaction mixture is then partitioned between water (200 mL) and EtOAc (200 mL)
3. extractionThe aqueous layer is extracted with EtOAc (1×200 mL)
4. washThe combined organic extracts are then washed with H2O (4×200 mL), saturated NaCl solution (2×200 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe resulting material is chromatographed (silica gel. 1:4 EtOAc-hexanes)