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

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.

1. temperatureThe reaction was heated
2. temperatureat reflux for 5 h
3. temperatureat reflux overnight
4. concentrationAfter this time, the reaction was concentrated in vacuo
5. washwashed with a 2N aqueous sodium hydroxide solution (2×250 mL)
6. washThe organics were then washed with a saturated aqueous sodium chloride solution (250 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. washrinsed
10. concentrationconcentrated in vacuo

ORD record

ord-4c53e8ab55e34b5bb845647c341b1388

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258134B2