1-(3,3,3-trifluoropropyl)piperazine;dihydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of [[(2S)-2-[[(2E)-3-(4-chlorophenyl)-2propenoyl]amino]-3-(2-pyridyl)propanoyl]amino]acetic acid (38.8 g), 1-(3,3,3-trifluoropropyl)piperazine dihydrochloride (25.5 g), 1-hydroxybenzotriazole (14.9 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (21.1 g) in N,N-dimethylformamide (250 ml) was added dropwise N,N-diisopropylethylamine (38.3 ml) at 10° C. over 50 minutes. The mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into ice-cold saturated aqueous sodium hydrogencarbonate solution (750 ml). The mixture was extracted three times with ethyl acetate (total 2500 ml) and washed successively with water (500 ml×3) and brine (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate) to give the title compound (37.0 g) as a white amorphous solid, which was recrystallized from ethyl acetate. The mixture was extracted three times with ethyl acetate (total 2500 ml) washed successively with water (500 ml×3) and brine (200 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated The residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl 4-(3,3,3-trifluoropropyl)-1-piperazinecarboxylate (5.77 g) in ethyl acetate (13 ml) and methanol (10 ml) was added dropwise 4N hydrogen chloride in ethyl acetate (29 ml) at 0° C. The mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with ethyl acetate. The resulting precipitate was collected by filtration, washed with ethyl acetate and dried in vacuo to give the title compound (4.70 g) as a pale yellow solid. The resulting precipitate was collected by filtration washed with ethyl acetate dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of [[(2S)-2-[[(2E)-3-(4-chlorophenyl)-2propenoyl]amino]-3-(2-pyridyl)propanoyl]amino]acetic acid (38.8 g), 1-(3,3,3-trifluoropropyl)piperazine dihydrochloride (25.5 g), 1-hydroxybenzotriazole (14.9 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (21.1 g) in N,N-dimethylformamide (250 ml) was added dropwise N,N-diisopropylethylamine (38.3 ml) at 10° C. over 50 minutes. The mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into ice-cold saturated aqueous sodium hydrogencarbonate solution (750 ml). The mixture was extracted three times with ethyl acetate (total 2500 ml) and washed successively with water (500 ml×3) and brine (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate) to give the title compound (37.0 g) as a white amorphous solid, which was recrystallized from ethyl acetate. The mixture was extracted three times with ethyl acetate (total 2500 ml) washed successively with water (500 ml×3) and brine (200 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated The residue was purified by silica gel column chromatography (eluent; 12% methanol in ethyl acetate)