Citric Acid → (3-{3-[2-(4-Methylbenzoyl)-1h-pyrrol-1-yl]-1-propynyl}phenoxy)acetic acid

Participants

Reaction Steps

To a solution of the compound (537 mg, 2.05 mmol) of Example 22-2 in tetrahydrofuran (8.0 ml) were added under ice cooling triethylamine (0.420 ml, 3.00 mmol) and methanesulfonyl chloride (0.170 ml, 2.20 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 (4.0 ml). Thereto was added lithium bromide (500 mg, 5.80 mmol) and the mixture was stirred for 1 hour. To the reaction mixture was added water and the mixture was 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 (259 mg, 1.40 mmol) of Reference example 1 and potassium t-butoxide (157 mg, 1.40 mmol) in tetrahydrofuran (4 ml) under ice cooling. The mixture was stirred for 7 hours under ice cooling. Thereto were added methanol (2.0 ml) and an aqueous 4N 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 the precipitate was taken by filtration. The precipitate was washed with a mixture of hexane and ether (1:1) and dried under reduced pressure to give the subject compound (529 mg, 95%) as white crystals.

Provenance & Evidence