Citric Acid → (4-Chloro-3-{(1e)-3-[2-(4-methylbenzoyl)-1h-pyrrol-1-yl]-1-propenyl}phenoxy)acetic acid

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Reaction Steps

To a solution of the compound of Example 20-4 in tetrahydrofuran (5.0 ml) were added under ice cooling triethylamine (0.270 ml, 1.94 mmol) and methanesulfonyl chloride (0.110 ml, 1.42 mmol) in the order. The mixture was stirred for 1 hour under ice cooling. To the reaction mixture were added cold 10% aqueous citric acid solution and the mixture was extracted with ethyl acetate. The organic layer was washed with cold 10% aqueous citric acid solution and a cold aqueous saturated sodium hydrogencarbonate solution in the order and dried over sodium sulfate. The solvent was removed and the residue was dissolve in tetrahydrofuran (2.0 ml). Thereto was added lithium bromide (2.61 mg, 3.00 mmol) and the mixture was stirred for 3 hours. To the reaction mixture was added water and extracted with ethyl acetate. The organic layer was washed with water and an aqueous saturated sodium chloride solution and dried over sodium sulfate. The solvent was removed and the residue was dissolved in tetrahydrofuran (2 ml). The solution was dropped into a solution of the compound (185 mg, 1.00 mmol) of Reference example 1 and potassium t-butoxide (112 mg, 1.00 mmol) in tetrahydrofuran (2 ml) under ice cooling. The mixture was stirred for 5 hours under ice cooling. Thereto were added methanol (2.0 ml) and an aqueous 1N sodium hydroxide solution (2.0 ml) and the mixture was stirred for 2 hours at room temperature. The reaction mixture was washed with hexane and ether and acidified with potassium hydrogensulfate. The mixture was extracted with chloroform and the organic layer was washed with an aqueous saturated sodium chloride solution and dried over sodium sulfate. The solvent was removed and purified with silica gel chromatography (chloroform:methanol, 10:1) to give the subject compound (177 mg, 29%).

Provenance & Evidence