Hydrochloric Acid → 4-(2-Pyridyl)Benzoic Acid

Participants

Reaction Steps

A solution of ethyl 3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-propylpropionate (2.20 g) in dioxane containing hydrogen chloride (4N, 30 ml) was allowed to stand at ambient temperature for 40 minutes. At the end of this time the reaction mixture was concentrated under reduced pressure and the hydrogen chloride was azeotropically distilled off with toluene to give a residue. A solution of diethyl cyanophosphonate (0.97 ml) in N,N-dimethylformamide (4.0 ml) was added to a solution of the residue obtained above (ethyl 3-[4-(2-aminoethoxy)phenyl]-2-propylpropionate hydrochloride), 4-pyridine-2-ylbenzoic acid (1.21 g) and triethylamine (1.80 ml) in N,N-dimethylformamide (8.0 ml) in an ice bath. The mixture was stirred for 1 hour in an ice bath and for 3 hours at ambient temperature. The reaction mixture was partitioned between ethyl acetate and water and the ethyl acetate was separated and washed with saturated aqueous sodium hydrogencarbonate and dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified via chromatography on a silica gel column using dichloroethane/ethyl acetate=7/3 as the eluant to give the title compound (2.20 g) as a pale yellow powder.

Provenance & Evidence