Potassium Carbonate → 2-[4-(4-Hydroxybutyl)phenoxymethyl]-3-thiophenecarboxylic acid methyl ester

Participants

Reaction Steps

To a stirred mixture of 8.31 g of 4-(4-hydroxyphenyl)butanol, 20.73 g of milled anhydrous potassium carbonate, 0.5 g of powdered potassium iodide and 200 ml of 2-butanone was added, over a few minutes, a solution of 9.45 g 2-chloromethyl-3-thiophenecarboxylic acid methyl ester and 20 ml of 2-butanone. The suspension was heated under reflux overnight, with stirring. The reaction mixture was filtered while hot, and the filter cake was washed with 2-butanone. The combined filtrate was concentrated. The residue was dissolved in 200 ml of dichloromethane, and the solution was washed with 200 ml of 5% sodium hydroxide solution, 200 ml of water and then saturated brine solution. The dried (over anhydrous sodium sulfate) organic phase was filtered and concentrated. The residue was purified by high-pressure liquid chromotography (Water Associates Prep LC/System 500; two silica gel columns; sample applied as a filtered solution in 200 ml of dichloromethane using a little pure dichloromethane to flush the material onto the column before elution; eluted with 10% (V/V) ethylacetate in dichloromethane; 150 ml/min. flow rate maintained until major component began to elute, then increased flow rate to 250 ml/min; U.V. and refractive index detectors used) to afford 10.38 g (65.3%) of product, m.p. 58°-60° C., after concentration and trituration of the eluents with hexane.

Provenance & Evidence