1,4-Dioxane → 2-Bromo-1-(6-chloropyridazin-3-yl)ethanone

Temperature

100 °C

To a stirring solution of dioxane (100 mL, degassed) was added 3,6-dichloropyridazine (5.0 g, 34 mmol), Cl2Pd(PPh3)2 (2.4 g, 3.4 mmol), and tributyl(1ethoxyvinyl)tin (18.2 g, 50 mmol). The reaction was heated to 100° C. and stirred for 1 h. The reaction was then concentrated, followed by the addition of EtOAc (100 mL) and potassium fluoride (50 mL of a saturated aqueous solution). The mixture was stirred for 30 min and then filtered through a pad of Celite. The filtrate was concentrated and then dissolved in THF (80 mL) and water (80 mL). NBS (18.1 g, 102 mmol) was then added, and the reaction was stirred for 20 min at rt. The reaction mixture was poured into ethyl acetate (200 mL), washed twice with brine (50 mL), dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography to afford 4.2 g of 2-bromo-1-(6-chloropyridazin-3-yl)ethanone.

1. concentrationThe reaction was then concentrated
2. additionfollowed by the addition of EtOAc (100 mL) and potassium fluoride (50 mL of a saturated aqueous solution)
3. stirringThe mixture was stirred for 30 min
4. filtrationfiltered through a pad of Celite
5. concentrationThe filtrate was concentrated
6. dissolutiondissolved in THF (80 mL)
7. stirringthe reaction was stirred for 20 min at rt
8. washwashed twice with brine (50 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. custompurified by silica gel chromatography

ORD record

ord-eb4f24be2ee2491ba4392f38f36d09db

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969346B2