Pivalic acid → 6-Hydroxy-2,5-quinolinedipropanoic Acid Diethyl Ester

Participants

Reaction Steps

A solution of 0.779 g (3.17 mmol) of 6-hydroxy-2-quinolinepropanoic acid ethyl ester from the preceding example, 1.11 g (6.38 mmol) of triethyl orthoacrylate and 0.491 g (4.81 mmol) of trimethylacetic acid in 21 mL of toluene was stirred at reflux for 16 hr. A solution of 0.283 g (1.62 mmol) of triethyl orthoacrylate in 3 mL of toluene was added and the reaction was allowed to stir under reflux for another 23 hr. After being cooled to room temperature, the solution was diluted with ether, washed three times with saturated aqueous sodium bicarbonate, and work-up was completed in the usual manner. To the residue was added 25 mL of ether, 25 mL of water and 1.21 g (6.36 mmol) of p-toluenesulfonic acid monohydrate and the resulting mixture was stirred at room temperature for 1.5 hr. Saturated aqueous sodium bicarbonate was added and the mixture was worked-up with ethyl acetate in the usual manner. The crude product was flash chromatographed on 110 g of silica gel, eluting with hexane-ethyl acetate (3:1 and 2:1) affording 0.909 g (82.9%) of the title compound as a white solid, mp 74°-76° C.

Provenance & Evidence