3,4-dihydro-2H-pyran → 4,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

Participants

Reaction Steps

A solution of 4,5-dichloropyridazin-3(2H)-one (10 g, 60.6 mmol) in tetrahydrofuran (60 mL, 1.0M) was treated with pyridinium para-toluene sulfonate (3.03 g, 12.1 mmol) and 3,4-dihydro-2H-pyran (8.5 mL, 93.2 mmol). The reaction was heated at reflux for 5 h and was then treated with a second aliquot of 3,4-dihydro-2H-pyran (5.5 mL, 60.3 mmol). The reaction was stirred at reflux overnight. After this time, the reaction was concentrated in vacuo, taken up in ethyl acetate (250 mL), and washed with a 2N aqueous sodium hydroxide solution (2×250 mL). The organics were then washed with a saturated aqueous sodium chloride solution (250 mL), dried over magnesium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (Biotage, 330 g, 10% ethyl acetate/hexanes) afforded 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (13.01 g, 86%) as an off-white solid; ES+-HRMS m/e calcd for C9H10N2O2Cl2 [M+Na+] 271.0011, found 271.0012.

Provenance & Evidence