p-Toluenesulfonic acid → 2-chloro-4-((tetrahydro-2H-pyran-2-yloxy)methyl)pyridine

Participants

Reaction Steps

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]+.

Provenance & Evidence