Phenyl chloroformate → 4-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]amide

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Reaction Steps

4-(2-Fluoro-4-nitrophenoxy)pyridin-2-ylamine (60 mg) was dissolved in tetrahydrofuran (3 ml) under a nitrogen atmosphere, and then triethylamine (0.101 ml) and phenyl chloroformate (0.0908 ml) were added thereto while cooling in an ice water bath, followed by warming to room temperature and stirring for 1.5 hrs. The solution was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, to which was added N,N-dimethylformamide (3 ml). 4-(Azetidin-1-ylmethyl)piperidine dihydrochloride (192 mg) and triethylamine (0.235 ml) were added thereto, followed by stirring for 8 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of ammonium chloride (50 ml). The organic layer was washed with a saturated aqueous solution of ammonium chloride (50 ml), water (50 ml), and brine (50 ml), and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, heptane:ethyl acetate=1:1, then ethyl acetate). Fractions containing the target compound were concentrated to provide the titled compound (34 mg) as a pale yellow oil.

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