Sodium Hydroxide → 4-{1-[6-(4-Trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoic acid

Participants

Reaction Steps

To a solution of 1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptan-1-ol (280 mg, 0.83 mmol) in THF (2 mL) and toluene (4 mL) is added 1,1′-(azodicarbonyl)dipiperidine (ADDP, 314.1 mg, 1.24 mmol) at 0° C., followed by the addition of tributylphosphine (0.31 mL, 1.24 mmol) and methyl 4-hydroxybenzoate (151.5 mg, 1 mmol). The reaction mixture is warmed up to room temperature and stirred overnight. The mixture is loaded on silica gel, eluted with hexanes with a gradient from 0% of ethyl acetate to 50% of ethyl acetate giving ethyl 4-{1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoate. The ester product is taken into ethanol (2 mL), treated with sodium hydroxide (5N aqueous, 1 mL) for 3 h at room temperature. The mixture is concentrated, diluted with ethyl acetate, acidified with 5 N HCl (1.1 mL), extracted with ethyl acetate. The organic layers are dried and concentrated giving 4-{1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-heptyloxy}-benzoic acid (330 mg).

Provenance & Evidence