4-Methylmorpholine → 1-[[5-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridin-2-yl]carbonyl]azetidin-3-ol

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Reaction Steps

To a solution of 1-(diphenylmethyl)azetidin-3-ol (230 mg, 0.961 mmol) in ethanol (10 ml), palladium-carbon (50 mg) was added, and the mixture was stirred for 1.5 hours in a hydrogen atmosphere. The reaction suspension was filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was dissolved in methylene chloride (10 ml), and 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (113 mg, 0.268 mmol) obtained in Example 12, 1-hydroxybenzotriazole (36 mg, 0.268 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (62 mg, 0.322 mmol) and 4-methylmorpholine (35 μl, 0.322 mmol) were added. The mixture was stirred for 4 days at room temperature. The reaction solution was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with methanol:methylene chloride (=1:40) was concentrated under reduced pressure, to obtain a solid. The obtained solid was washed with ethanol, and then was collected by filtration to obtain the title compound (72 mg, 0.151 mmol, 56%) as a white powder.

Provenance & Evidence