Pyridine → HCID 21091632, compound

Participants

Reaction Conditions

Reaction Steps

2.5 g (0.015 mol) of 4-(3-hydroxyphenyl)pyridine and 40 ml of pyridine and 2.3 g of 4-(dimethylamino)pyridine (DMAP) are cooled to 0° C. 3.2 ml of triflic anhydride are added thereto dropwise. The mixture is stirred at 0° C. for one hour and at ambient temperature overnight. It is poured into a water/ice mixture, extraction is carried out with ethyl acetate, the organic phase is dried and the solvent is evaporated under reduced pressure. The crude product is purified by chromatography on a column of silica gel, elution being carried out with a cyclohexane/ethyl acetate=8/2 mixture. 4-(3-Hydroxyphenyl)pyridine trifluoromethanesulfonate is obtained in the form of an oil. 2.26 g of this product are mixed with 112 ml of anhydrous dimethylformamide, 38 g of palladium acetate, 2.5 ml of anhydrous triethylamine and 2 g of N,N-dimethylethanolamine vinyl ether. The mixture is heated at 80° C. for 48 hours. The solvent is evaporated under reduced pressure. The residue is purified by flash chromatography on a column of silica gel, elution being carried out with ethyl acetate, to remove the first product, and subsequently with an ethyl acetate/methanol=1/1 mixture. 2-[2-[3-(4-Pyridyl)-phenyl)ethenyl)oxy)]-N,N-dimethyl-1-ethanamine is obtained. 0.53 g of this product, dissolved in 35 ml of methanol, is treated with 20 ml of water and 5 ml of 96% sulfuric acid. The mixture is heated at 60° C. for 6 hours and is poured into ice, a saturated aqueous NaHCO3 solution is added thereto and extraction is carried out with ethyl acetate. The organic phase is dried and the solvent is evaporated under reduced pressure. 3-(4-Pyridyl)phenylacetaldehyde dimethyl acetal is obtained. Its N-oxide derivative is prepared by reaction with m-chloroperbenzoic acid in methylene chloride and the aldehyde is subsequently released by reaction with a mixture of trifluoroacetic acid, water and methylene chloride. The title compound is thus obtained.

Provenance & Evidence