6-(2,2-difluoro-2-phenylethoxy)hexan-1-amine

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:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (8-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)quinolin-2(1H)-one (4.80 g, 9.83 mmol) and Intermediate 9 (3.04 g, 11.8 mmol) in dimethylsulfoxide (13.5 mL) was added sodium bicarbonate (2.49 g, 29.4 mmol) and sodium iodide (2.22 g, 14.8 mmol). The mixture was heated at 140° C. for 2 hours. After cooling, the reaction was diluted with water (40 mL) and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with water (2×10 mL) and brine (20 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.40 g, 98%) as oil. After cooling extracted with diethyl ether (2×20 mL) The combined organic extracts were washed with water (2×10 mL) and brine (20 mL) dried (Na2SO4) the solvent removed under reduced pressure

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

実験手順: To a solution of Intermediate 8 (6.41 g, 16.5 mmol) in ethanol (50 ml) was added hydrazine monohydrate (12 mL, 247 mmol). The mixture was stirred at room temperature overnight, concentrated, and the residue was triturated with isopropyl alcohol. The resulting solid was filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography with silica gel, eluting with methylene chloride/ethanol/ammonium hydroxide (80:8:1) to give the title compound (2.31 g, 54%) as oil. concentrated the residue was triturated with isopropyl alcohol The resulting solid was filtered the solvent removed under reduced pressure The residue was purified by column chromatography with silica gel eluting with methylene chloride/ethanol/ammonium hydroxide (80:8:1)

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (8-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)quinolin-2(1H)-one (V) (4.80 g, 9.83 mmol) and 6-(2,2-Difluoro-2-phenylethoxy)hexyl]amine (IV) (3.04 g, 11.8 mmol) in dimethylsulfoxide (13.5 mL) was added sodium bicarbonate (2.49 g, 29.4 mmol) and sodium iodide (2.22 g, 14.8 mmol). The mixture was heated at 140° C. for 2 hours. After cooling, the reaction was diluted with water (40 mL) and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with water (2×10 mL) and brine (20 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.40 g, 98%) as oil. After cooling extracted with diethyl ether (2×20 mL) The combined organic extracts were washed with water (2×10 mL) and brine (20 mL) dried (Na2SO4) the solvent removed under reduced pressure

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:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (8-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)quinolin-2(1H)-one (V) (4.80 g, 9.83 mmol) and 6-(2,2-Difluoro-2-phenylethoxy)hexyl]amine (IV) (3.04 g, 11.8 mmol) in dimethylsulfoxide (13.5 mL) was added sodium bicarbonate (2.49 g, 29.4 mmol) and sodium iodide (2.22 g, 14.8 mmol). The mixture was heated at 140° C. for 2 hours. After cooling, the reaction was diluted with water (40 mL) and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with water (2×10 mL) and brine (20 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.40 g, 98%) as oil. After cooling extracted with diethyl ether (2×20 mL) The combined organic extracts were washed with water (2×10 mL) and brine (20 mL) dried (Na2SO4) the solvent removed under reduced pressure

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (8-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)quinolin-2(1H)-one (4.80 g, 9.83 mmol) and Intermediate 9 (3.04 g, 11.8 mmol) in dimethylsulfoxide (13.5 mL) was added sodium bicarbonate (2.49 g, 29.4 mmol) and sodium iodide (2.22 g, 14.8 mmol). The mixture was heated at 140° C. for 2 hours. After cooling, the reaction was diluted with water (40 mL) and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with water (2×10 mL) and brine (20 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.40 g, 98%) as oil. After cooling extracted with diethyl ether (2×20 mL) The combined organic extracts were washed with water (2×10 mL) and brine (20 mL) dried (Na2SO4) the solvent removed under reduced pressure

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

実験手順: Obtained from Intermediate 31 (4.0 g, 14.4 mmol) by the procedure described in Intermediate 9. {6-[2,2-Difluoro-2-(3-methylphenyl)ethoxy]hexyl}amine was obtained (1.93 g, 50%) as oil.

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

実験手順: To a solution of Intermediate 8 (6.41 g, 16.5 mmol) in ethanol (50 mL) was added hydrazine monohydrate (12 mL, 247 mmol). The mixture was stirred at room temperature overnight, concentrated, and the residue was triturated with isopropyl alcohol. The resulting solid was filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography with silica gel, eluting with methylene chloride/ethanol/ammonium hydroxide (80:8:1) to give the title compound (2.31 g, 54%) as oil. concentrated the residue was triturated with isopropyl alcohol The resulting solid was filtered the solvent removed under reduced pressure The residue was purified by column chromatography with silica gel eluting with methylene chloride/ethanol/ammonium hydroxide (80:8:1)

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (8-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)quinolin-2(1H)-one (4.80 g, 9.83 mmol) and Intermediate 9 (3.04 g, 11.8 mmol) in dimethylsulfoxide (13.5 mL) was added sodium bicarbonate (2.49 g, 29.4 mmol) and sodium iodide (2.22 g, 14.8 mmol). The mixture was heated at 140° C. for 2 hours. After cooling, the reaction was diluted with water (40 mL) and extracted with diethyl ether (2×20 mL). The combined organic extracts were washed with water (2×10 mL) and brine (20 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.40 g, 98%) as oil. After cooling extracted with diethyl ether (2×20 mL) The combined organic extracts were washed with water (2×10 mL) and brine (20 mL) dried (Na2SO4) the solvent removed under reduced pressure