Hydrochloric Acid → 3-Hydroxy-2-(6-trifluoromethylpyridin-3-yl)-acrylic acid ethyl ester

Participants

Reaction Steps

3.46 g (14.8 mmol) of the compound from Example 40A are initially introduced into 50 ml anhydrous toluene under argon, 712 mg (17.8 mmol) sodium hydride suspension (60% strength in paraffin oil) are added in portions and the mixture is stirred at RT for 1 h and then at 80° C. for 20 min. After cooling, 392 mg (1.48 mmol) 18-crown-6 and then, while cooling with ice, 2.20 g (29.7 mol) formic acid ethyl ester are added dropwise. The mixture is stirred first at 0° C. for 1 h and then at RT for 1 h. A mixture of 100 ml ethyl acetate and 150 ml 0.1 M hydrochloric acid is added, the phases are separated, the aqueous phase is extracted several times with ethyl acetate and the combined organic phases are dried over sodium sulfate, filtered and concentrated. The residue is purified by means of flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient).

Provenance & Evidence