反应详情

To a mixture of (2-chloropyridin-4-yl)methanol (7.0 g, 48.8 mmol) and 3,4-dihydro-2H-pyran (20.5 g, 244 mmol) in THF (80 mL), 4-methylbenzenesulfonic acid (840 mg, 4.88 mmol) was added. The reaction mixture was stirred at reflux overnight, and the solvent was removed under reduced pressure. The residue was diluted with H2O (200 mL), and the aqueous phase was extracted with EtOAc (3×200 mL). The combined organic layers were washed with H2O (20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by silica gel column chromatography (Petroleum ether:EtOAc=4:1) to afford 2-chloro-4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridine as a yellow oil (8.7 g, 78%). MS (ES+) C11H14ClNO2 requires: 227, found: 228[M+H]+.

1. additionwas added
2. temperatureat reflux overnight
3. customthe solvent was removed under reduced pressure
4. additionThe residue was diluted with H2O (200 mL)
5. extractionthe aqueous phase was extracted with EtOAc (3×200 mL)
6. washThe combined organic layers were washed with H2O (20 mL) and brine (20 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto afford the crude product, which
11. customwas purified by silica gel column chromatography (Petroleum ether:EtOAc=4:1)