Sodium Hydroxide → 4-(3-Dimethylaminoazetidin-1-yl)piperidine-1-carboxylic acid [4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]amide

Participants

Reaction Steps

To a solution of 4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylamine (140 mg) in tetrahydrofuran (7.0 ml) were added triethylamine (0.172 ml) and phenyl chloroformate (0.141 ml) in this order at room temperature, followed by stirring at room temperature for 30 min. The reaction mixture was concentrated to give a residue. To the residue were added N,N-dimethylformamide (5.0 ml), triethylamine (0.940 ml), N,N-Dimethyl-N-[1-(piperidin-4-yl)azetidin-3-yl]amine trihydrochloride (658 mg) and water (0.050 ml), followed by stirring at room temperature for 2 days. An 1N aqueous solution of sodium hydroxide (30 ml) was added thereto, followed by stirring at room temperature for 5 hrs. The reaction mixture was extracted with ethyl acetate (100 ml). The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated to provide the titled compound (258 mg, 100%) as a pale yellow oil.

Provenance & Evidence