Citric Acid → Ethyl 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl)-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate

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Reaction Steps

Add 0.257 g (2.11 mmol) of 3-chloro-N,N-dimethylpropane-1-amine hydrochloride and 3.40 g (1.34 mmol) of caesium carbonate to a solution of 0.5 g (1.21 mmol) of ethyl 6-(4-chloro-3-hydroxyphenyl)-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate in 20 mL of anhydrous DMF under argon. Stir the reaction mixture for 15 min at RT then heat for 2 h at 80° C. After cooling to RT, add 1 mL of an aqueous solution of citric acid at 5% and concentrate the whole under reduced pressure. Take up the residue in 50 mL of EtOAc and wash with 10 mL of a 5% solution of Na2CO3 and then 10 mL of water. After drying over Na2SO4 and concentration under reduced pressure, purify the residue by silica gel column chromatography, eluting with a DCM/methanol gradient from 1 to 15% of methanol. After concentration under reduced pressure, we obtain 0.55 g of ethyl 6-{4-chloro-3-[3-(dimethylamino)propoxy]phenyl}-5-(2,6-dimethoxyphenyl)pyridine-2-carboxylate in the form of oil.

Provenance & Evidence