(Trifluoromethyl)trimethylsilane → Ethyl 2-methyl-2-[4-(2-{[5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl][4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]propanoate

Participants

Reaction Steps

A solution of ethyl 2-[4-(2-{(5-formylpyridin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (400 mg; 0.75 mmol) in 5 ml of dry THF was treated in an ice bath, under nitrogen, with trifluoromethyltrimethylsilane (128 mg; 0.90 mmol), followed by tetrabutylammonium fluoride (0.075 ml of a 1M solution in THF; 0.075 mmol). The reaction mixture was allowed to warm to rt and stirred overnight. Additional trifluoromethyltrimethylsilane (128 mg; 0.90 mmol) and tetrabutylammonium fluoride (0.075 ml) were added. After 6 hours the previous reagents were added again in the same amounts. After stirring at rt overnight, the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over sodium sulfate and concentrated. Purification by radial chromatography using ethyl acetate-hexane mixtures (5–40% gradient) afforded ethyl 2-methyl-2-[4-(2-{[5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl][4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]propanoate (247 mg; 55% yield).

Provenance & Evidence