2-(2,2,2-trifluoroethoxy)aniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 2-(2,2,2-trifluoroethoxy)aniline (2.85 g, 14.9 mmol), bis(2-chloroethyl)amine hydrochloride (2.66 g, 14.9 mmol), potassium carbonate (2.06 g, 14.9 mmol), sodium iodide (0.45 g, 3 mmol) and bis(2-methoxyethyl) ether (7.3 mL) was heated 8 hours at reflux. The reaction mixture then was cooled, treated with concentrated ammonium hydroxide, poured into water (30 mL) and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with water (2×30 mL) and brine (1×30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5) to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.93 g, 11.2 mmol), m.p. 107°-108° C. was heated 8 hours at reflux The reaction mixture then was cooled extracted with ethyl acetate (3×30 mL) The combined extracts were washed with water (2×30 mL) and brine (1×30 mL) dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(2,2,2-trifluoroethoxy)-2-nitrobenzene (15 g, 68 mmol), platinum oxide hydrate (100 mg) and absolute ethanol (80 mL) was hydrogenated 18 hours with stirring at 25° C. and 15 psi of pressure. The reaction mixture then was filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (9:1) to give 2-(2,2,2-trifluoroethoxy)aniline (10.4 g, 54.5 mol), m.p. 49°-50° C. The reaction mixture then was filtered concentrated The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (9:1)

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

実験手順: A mixture of 2-(2,2,2-trifluoroethoxy)aniline (2.85 g, 14.9 mmol), bis(2-chloroethyl)amine hydrochloride (2.66 g, 14.9 mmol), potassium carbonate (2.06 g, 14.9 mmol), sodium iodide (0.45 g, 3 mmol) and bis(2-methoxyethyl) ether (7.3 mL) was heated 8 hours at reflux. The reaction mixture then was cooled, treated with concentrated ammonium hydroxide, poured into water (30 mL) and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with water (2×30 mL) and brine (1×30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5) to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.93 g, 11.2 mmol), m.p. 107°-108° C. was heated 8 hours at reflux The reaction mixture then was cooled extracted with ethyl acetate (3×30 mL) The combined extracts were washed with water (2×30 mL) and brine (1×30 mL) dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(2,2,2-trifluoroethoxy)-2-nitrobenzene (15 g, 68 mmol), platinum oxide hydrate (100 mg) and absolute ethanol (80 mL) was hydrogenated 18 hours with stirring at 25° C. and 15 psi of pressure. The reaction mixture then was filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (9:1) to give 2-(2,2,2-trifluoroethoxy)aniline (10.4 g, 54.5 mol), m.p. 49°-50° C. The reaction mixture then was filtered concentrated The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (9:1)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 2-(2,2,2-trifluoroethoxy)aniline (3.89 g, 20.4 mmol), bis(2-chloroethyl)amine hydrochloride (3.64 g, 20.4 mmol), potassium carbonate (2.82 g, 20.4 mmol) and sodium iodide (0.6 g, 4.1 mmol) in 10 mL of 2-methoxyethyl ether was heated at reflux for 4.5 hours. The mixture was cooled and 20 mL of an aqueous solution at pH 9 was added. The mixture was extracted with ethyl acetate (4×50 mL) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with 5% methanol/methylene chloride to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.74 g, 10.6 mmol). The free base was recrystallized from hydrochloric acid in alcohol to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine hydrochloride, m.p. 172°-173° C. was heated at reflux for 4.5 hours The mixture was cooled The mixture was extracted with ethyl acetate (4×50 mL) the combined organic layers were washed with brine dried (Na2SO4) concentrated The residue was purified on silica gel by column chromatography eluting with 5% methanol/methylene chloride

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

実験手順: A mixture of 2-(2,2,2-trifluoroethoxy)aniline (3.89 g, 20.4 mmol), bis(2-chloroethyl)amine hydrochloride (3.64 g, 20.4 mmol), potassium carbonate (2.82 g, 20.4 mmol) and sodium iodide (0.6 g, 4.1 mmol) in 10 mL of 2-methoxyethyl ether was heated at reflux for 4.5 hours. The mixture was cooled and 20 mL of an aqueous solution at pH 9 was added. The mixture was extracted with ethyl acetate (4×50 mL) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with 5% methanol/methylene chloride to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.74 g, 10.6 mmol). The free base was recrystallized from hydrochloric acid in alcohol to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine hydrochloride, m.p. 172°-173° C. was heated at reflux for 4.5 hours The mixture was cooled The mixture was extracted with ethyl acetate (4×50 mL) the combined organic layers were washed with brine dried (Na2SO4) concentrated The residue was purified on silica gel by column chromatography eluting with 5% methanol/methylene chloride

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 200-ml round-bottom flask is charged with conc. HCl (4 ml) and water (40 ml), and 2-(2,2,2trifluoroethoxy)aniline (3.82 g) is added. The resulting solution is cooled at a temperature of not more than 5° C. and an aqueous solution consisting of sodium nitrite (1.7 g) dissolved in water (10 ml) is added dropwise with tile temperature held at 4° C. or below, followed by stirring For one hour. In a separate step, 3-mercapto-1,2,4-triazole (4.5 g) and potassium hydroxide (2.2 g) is dissolved in water (40 ml) to give an aqueous solution which is cooled at 0° C. A preliminarily prepared diazonium salt solution is added dropwise to this aqueous solution. Thereafter, the resulting mixture is stirred at room temperature for about one hour. The organic layer is extracted with ethyl acetate, washed with water and dried. The solvent is distilled off and the resulting crude crystal is recrystallized with a mixed solvent of n-hexane and ethyl acetate; yield 4.4 g (71 %); m.p. 100°-101° C. is added The resulting solution is cooled at a temperature of not more than 5° C. is added dropwise with tile temperature held at 4° C. or below to give an aqueous solution which Thereafter, the resulting mixture is stirred at room temperature for about one hour The organic layer is extracted with ethyl acetate washed with water dried The solvent is distilled off the resulting crude crystal is recrystallized with a mixed solvent of n-hexane and ethyl acetate

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

実験手順: A mixture of 2-(2,2,2-trifluoroethoxy)aniline (2.85 g, 14.9 mmol), bis(2-chloroethyl)amine hydrochloride (2.66 g, 14.9 mmol), potassium carbonate (2.06 g, 14.9 mmol), sodium iodide (0.45 g, 3 mmol) and bis(2-methoxyethyl) ether (7.3 mL) was heated 8 hours at reflux. The reaction mixture then was cooled, treated with concentrated ammonium hydroxide, poured into water (30 mL) and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with water (2×30 mL) and brine (1×30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5) to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.93 g, 11.2 mmol), m.p. 107°-108° C. was heated 8 hours at reflux The reaction mixture then was cooled extracted with ethyl acetate (3×30 mL) The combined extracts were washed with water (2×30 mL) and brine (1×30 mL) dried (MgSO4) concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(2,2,2-trifluoroethoxy)-2-nitrobenzene (15 g, 68 mmol), platinum oxide hydrate (100 mg) and absolute ethanol (80 mL) was hydrogenated 18 hours with stirring at 25° C. and 15 psi of pressure. The reaction mixture then was filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (9:1) to give 2-(2,2,2-trifluoroethoxy)aniline (10.4 g, 54.5 mol), m.p. 49°-50° C. The reaction mixture then was filtered concentrated The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (9:1)