反应详情

Zinc chloride (2.04 g, 15.0 mmol) was dried at 180° C. for 2 hours under vacuum and then cooled to room temperature, and anhydrous tetrahydrofuran (20.0 mL) was added thereto. n-Butyl lithium (1.6 M, 9.0 mL, 14.4 mmol) was added dropwise thereto over about 30 minutes under ice-cooling and stirred for 30 minutes under ice-cooling, to prepare a solution of n-butylzinc chloride in tetrahydrofuran. Separately, a suspension of 2,6-dichloroimidazo[1,2-b]pyridazine (1.88 g, 10.0 mmol) and [1,3-bis(diphenylphosphino)propane]nickel(II) dichloride (0.16 g, 0.30 mmol) in anhydrous tetrahydrofuran (20.0 mL) was prepared under a nitrogen atmosphere, and the previously prepared solution of n-butylzinc chloride in tetrahydrofuran was added dropwise thereto over 30 minutes with maintaining at 3 to 6° C. The mixture was stirred for 15 minutes under ice-cooling and for 3 hours at room temperature, poured into a saturated saline and adjusted to pH 2 with dilute hydrochloric acid. The reaction solution was extracted twice with ethyl acetate, and the extracts were combined, dehydrated over anhydrous magnesium sulfate and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to give the title compound as pale yellow crystals. The yield was 2.03 g (96.8%).

1. temperatureover about 30 minutes under ice-cooling
2. temperaturecooling
3. customwas prepared under a nitrogen atmosphere
4. temperatureover 30 minutes with maintaining at 3 to 6° C
5. stirringThe mixture was stirred for 15 minutes under ice-
6. temperaturecooling and for 3 hours at room temperature
7. additionpoured into a saturated saline
8. extractionThe reaction solution was extracted twice with ethyl acetate
9. concentrationconcentrated under reduced pressure
10. customThe residues were purified by silica gel column chromatography (ethyl acetate:hexane=1:4)