1253-47-0 → trans 4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid methyl ester

Participants

Reaction Steps

(4-Methoxycarbonyl-benzyl)-triphenyl-phosphonium chloride (6.7 g, 15 mmol) is suspended in anhydrous toluene (25 mL) and potassium tert-butoxide (1.7 g, 15 mmol) is added at room temperature in one portion. The mixture is allowed to stir under nitrogen for 1 h. Meanwhile, 5,5,5-trifluoro-2-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-pentanal (3.61 g, 10.0 mmol) is dissolved in another portion of the toluene (25 mL), and kept at room temperature. The mixture is then cooled to 0° C. with ice water, and then the ketone is transferred by cannula. The reaction is allowed to stir at 0° C. for 10 min, then the ice bath is removed. The reaction is allowed to warm to room temperature and monitored by HPLC. Upon complete conversion, the reaction is carefully quenched with saturated ammonium chloride solution, and diluted with ethyl acetate, then extracted. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, then filtered and concentrated. The cis and trans 4-{6,6,6-Trifluoro-3-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-hex-1-enyl}-benzoic acid methyl ester (2.0 g, 4.1 mmol) are isolated as pure regioisomers (1:1) after column chromatography, 31% total yield.

Provenance & Evidence