Dimethylformamide → 3-(3,5-Dimethoxypyridin-4-yl)propenoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

3,5-Dimethoxypyridine (8.1 g, 58 mmol) is dissolved in THF (100 ml), and thereto is added a solution of n-butyl lithium in hexane (45.3 ml, 70 mmol) at −20° C., and the mixture is warmed to 0° C. The mixture is stirred for 30 minutes, and cooled to −78° C. To the mixture is added DMF (5.4 ml, 70 mmol), and the mixture is warmed to 0° C. over a period of time for 30 minutes. Then, to the reaction solution is added a solution of a salt which is prepared from triethylphosphonoacetate (15.6 g, 69 mmol) and sodium hydride (60% in mineral oil, 2.78 g, 69 mmol) in THF (50 ml) at 0° C., and the mixture is stirred for one hour. The reaction solution is poured into ice-water, extracted with ethyl acetate (200 ml×2), washed with a saturated brine (100 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent; chloroform/methanol), and further recrystallized from isopropyl ether/hexane to give the title compound (7.3 g) as colorless crystals, m.p. 100-101° C.

Provenance & Evidence