Hydrochloric Acid → 3-(6-Chloropyridin-3-YL)-3-oxopropanenitrile

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Reaction Steps

3-(2-Chloropyridin-5-yl)-3-oxopropionitrile was prepared by treating a solution of cyanoacetic acid (9.10 g, 53.5 mmol) and 2,2′-bipyridyl (5 mg) in dry THF (500 ml), cooled to −70° under a nitrogen atmosphere, dropwise with n-butyllithium (85.6 ml, 214 mmol of a 2.5M solution in hexane). The reaction was allowed to warm to 0° over a period of 1 h and then recooled to −70°, at which point a solution of 6-chloronicotinyl chloride (9.42 g, 53.5 mmol) in THF (75 ml) was added to the resulting red slurry. The reaction was stirred at −70° for a further 1 h upon complete addition, and then allowed to reach 0° where upon 2M hydrochloric acid (250 ml) was added. The reaction was extracted with chloroform (2×400 ml) and the combined organic phases were then washed with saturated aqueous NaHCO3 (1×250 ml) and saturated brine (1×250 ml), dried (MgSO4) and concentrated under reduced pressure. The resulting solid was triturated with diethyl ether/n-hexane (1:5) to give the desired material (4.20 g) as a pale yellow powder m.p. 122-123°.

Provenance & Evidence