Hydrochloric Acid → 3-(1,5-diphenyl-1H-pyrazol-4-yl)propionic acid

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Reaction Steps

To a mixture of (1,5-diphenyl-1H-pyrazol-4-yl)methanol (11.78 g), triethylamine (10 ml) and ethyl acetate (300 ml) was added dropwise methanesulfonyl chloride (4.5 ml) at 0° C. The mixture was stirred at room temperature for 1 hr. and the ethyl acetate layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. This oil was dissolved in N,N-dimethylformamide (100 ml) and the resulting solution was added dropwise to a solution of sodium diethyl malonate in N,N-dimethylformamide (prepared using diethyl malonate 20.33 g, sodium hydride (60% in oil, 4.88 g) and N,N-dimethylformamide 200 ml) at 0° C. The mixture was stirred at room temperature for 5 hrs., and poured into a 1N aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with a 1N aqueous hydrochloric acid solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give an oil. A mixture of this oil, a 6N aqueous hydrochloric acid solution (100 ml) and acetic acid (50 ml) was heated under reflux for 5 hrs. The reaction mixture was cooled, concentrated and poured into water. The precipitated crystals were collected by filtration, washed with water, and dried to give 3-(1,5-diphenyl-1H-pyrazol-4-yl)propionic acid. yield: 68%. colorless needle crystals. melting point: 159-160° C. (recrystallized from acetone-hexane).

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