Triphenylphosphine → 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine

Participants

Reaction Conditions

Reaction Steps

Triphenylphosphine (6.88 g, 26.2 mmol) was added to a mixture of tetrahydro-2H-pyran-4-ol (2.68 g, 26.2 mmol) and 2-chloropyridin-4-ol (2.72 g, 21.00 mmol) in THF (70 mL) under argon. Diisopropyl azodicarboxylate (DIAD) (5.28 mL, 26.9 mmol) was added dropwise over 5 mins and then the mixture was heated to 55° C. overnight. The mixture was cooled to RT and the solvent was removed in vacuo to give an oil. The oil was purified by silica gel chromatography to give crude 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine as an oil. This material was dissolved in ethyl acetate and then washed with 1N aqueous sodium hydroxide, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine (3.71 g, 17.4 mmol, 83% yield) as a light yellow solid.

Provenance & Evidence