p-Toluenesulfonic acid → 5-Iodo-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one

Temperature

25 °C

A mixture of 5-iodo-2H-pyridazin-3-one (8.640 g, 38.92 mmol) in tetrahydrofuran (150 mL) was treated with para-toluenesulfonic acid (1.49 g, 7.86 mmol) and 3,4-dihydro-2H-pyran (8.98 mL, 98.18 mmol). The reaction was stirred at 25° C. for 2 d. After this time, the reaction was filtered. The filtrate was treated with para-toluenesulfonic acid (6 g) and 3,4-dihydro-2H-pyran (9 mL), and the reaction stirred at 25° C. for 6 h. The reaction was concentrated in vacuo, taken up in ethyl acetate (400 mL), washed with a saturated aqueous sodium bicarbonate solution (400 mL), and a saturated aqueous sodium chloride solution. The aqueous layer was extracted with ethyl acetate (300 mL) and was washed with a saturated aqueous sodium chloride solution. The combined organics were dried over sodium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 400 g, 0% to 50% ethyl acetate/hexanes) afforded 5-iodo-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (2.73 g, 23%) as a clear light brown, viscous oil. The material contained an impurity. However, it was used without further purification.

1. filtrationAfter this time, the reaction was filtered
2. additionThe filtrate was treated with para-toluenesulfonic acid (6 g) and 3,4-dihydro-2H-pyran (9 mL)
3. stirringthe reaction stirred at 25° C. for 6 h
4. concentrationThe reaction was concentrated in vacuo
5. washwashed with a saturated aqueous sodium bicarbonate solution (400 mL)
6. extractionThe aqueous layer was extracted with ethyl acetate (300 mL)
7. washwas washed with a saturated aqueous sodium chloride solution
8. dry with materialThe combined organics were dried over sodium sulfate
9. filtrationfiltered
10. washrinsed
11. concentrationconcentrated in vacuo

ORD record

ord-bb102e2cb4254d009eab72040701c773

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258134B2