1-bromo-2-(1-bromoethyl)benzene

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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

実験手順: To a cooled solution (−78° C.) of N-pyridin-3-ylpyridin-3-amine (0.886 g, 5.23 mmol) in dry tetrahydrofuran (20 mL) was added LDA (3.8 mL of a 1.5 M solution, 5.75 mmol) to form a light yellow suspension. After stirring for 30 min, 1-bromo-2-(1-bromoethyl)benzene (3-1) (1.38 g, 5.23 mmol) was added in one portion. The reaction was stirred for 30 min at −78° C. then allowed to warmn to 0° C. and quenched with NH4Cl sat. solution (6 mL). The mixture was diluted with water and extracted with THF (2×20 mL), washed with brine and the organic layer was dried over Na2SO4. The solution was then filtered, concentrated, and dried under vacuum to give crude N-(1-(2-bromophenyl)ethyl)-N-(pyridin-3-yl)pyridin-3-amine (3-2) as a light brown solid (4.40 g): Analytical LCMS: (214 nm), 2.043 min. m/e (m+1): 356.1 to form a light yellow suspension The reaction was stirred for 30 min at −78° C. to warmn to 0° C. quenched with NH4Cl sat. solution (6 mL) The mixture was diluted with water extracted with THF (2×20 mL) washed with brine the organic layer was dried over Na2SO4 The solution was then filtered concentrated dried under vacuum

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

実験手順: To a cooled solution (−78° C.) of N-pyridin-3-ylpyridin-3-amine (0.886 g, 5.23 mmol) in dry tetrahydrofuran (20 mL) was added LDA (3.8 mL of a 1.5 M solution, 5.75 mmol) to form a light yellow suspension. After stirring for 30 min, 1-bromo-2-(1-bromoethyl)benzene (3-1) (1.38 g, 5.23 mmol) was added in one portion. The reaction was stirred for 30 min at −78° C. then allowed to warmn to 0° C. and quenched with NH4Cl sat. solution (6 mL). The mixture was diluted with water and extracted with THF (2×20 mL), washed with brine and the organic layer was dried over Na2SO4. The solution was then filtered, concentrated, and dried under vacuum to give crude N-(1-(2-bromophenyl)ethyl)-N-(pyridin-3-yl)pyridin-3-amine (3-2) as a light brown solid (4.40 g): Analytical LCMS: (214 nm), 2.043 min. m/e (m+1): 356.1 to form a light yellow suspension The reaction was stirred for 30 min at −78° C. to warmn to 0° C. quenched with NH4Cl sat. solution (6 mL) The mixture was diluted with water extracted with THF (2×20 mL) washed with brine the organic layer was dried over Na2SO4 The solution was then filtered concentrated dried under vacuum

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness

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

実験手順: To a cooled solution (−78° C.) of N-pyridin-3-ylpyridin-3-amine (0.886 g, 5.23 mmol) in dry tetrahydrofuran (20 mL) was added LDA (3.8 mL of a 1.5 M solution, 5.75 mmol) to form a light yellow suspension. After stirring for 30 min, 1-bromo-2-(1-bromoethyl)benzene (3-1) (1.38 g, 5.23 mmol) was added in one portion. The reaction was stirred for 30 min at −78° C. then allowed to warmn to 0° C. and quenched with NH4Cl sat. solution (6 mL). The mixture was diluted with water and extracted with THF (2×20 mL), washed with brine and the organic layer was dried over Na2SO4. The solution was then filtered, concentrated, and dried under vacuum to give crude N-(1-(2-bromophenyl)ethyl)-N-(pyridin-3-yl)pyridin-3-amine (3-2) as a light brown solid (4.40 g): Analytical LCMS: (214 nm), 2.043 min. m/e (m+1): 356.1 to form a light yellow suspension The reaction was stirred for 30 min at −78° C. to warmn to 0° C. quenched with NH4Cl sat. solution (6 mL) The mixture was diluted with water extracted with THF (2×20 mL) washed with brine the organic layer was dried over Na2SO4 The solution was then filtered concentrated dried under vacuum

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

実験手順: To a solution of sodium ethoxide in ethanol obtained from 15.4 g (0.67 mmol) of sodium and 360 ml of anhydrous ethanol, a solution of 215 g (1.34 mmol) of diethyl malonate in 240 ml of ethanol was added dropwise, while vigorously stirring, over 15 min. Then, 137 g (0.52 mmol) of 1-bromo-2-(1-bromoethyl)benzene in 50 ml of ethanol was added dropwise with such a rate, so the reaction mixture would be slowly refluxing. The resulting mixture was additionally refluxed for 4 h, then cooled to room temperature, and a solution of 105 g of potassium hydroxide in 280 ml of water was added. This mixture was refluxed for 3 h, and then ethanol was distilled off at atmospheric pressure. The solution obtained was cooled to ambient temperature and acidified by saturated hydrochloric acid to pH 1. The precipitate formed was filtered off, washed with 2×200 ml of cold water, and dried in air. The dibacic acid obtained was then dehcarboxylated by heating it at 160° C. for 2 h. To the viscous oil obtained, 130 ml of SOCl2 was added, and the resulting mixture was stirred for 24 h at room temperature. The excess of SOCl2 was distilled off, and the residue was dissolved in 160 ml of anhydrous dichloromethane. The solution obtained was added dropwise to a suspension of 80.0 g (0.60 mmol) of AlCl3 in 800 ml of dichloromethane for 1 h at 0° C. The reaction mixture was refluxed for 3 h, then cooled to room temperature, poured on 500 cm3 of ice, and finally acidified by saturated HCl to pH 3. The organic layer was separated, and the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether. The combined organic extract was dried over K2CO3 and then evaporated to dryness. The title product was isolated fractional distillation in vacuum, bp 108-112° C./3 mm Hg. Yield 101 g (86%). so the reaction mixture would be slowly refluxing The resulting mixture was additionally refluxed for 4 h This mixture was refluxed for 3 h ethanol was distilled off at atmospheric pressure The solution obtained was cooled to ambient temperature The precipitate formed was filtered off washed with 2×200 ml of cold water dried in air The dibacic acid obtained by heating it at 160° C. for 2 h To the viscous oil obtained the resulting mixture was stirred for 24 h at room temperature The excess of SOCl2 was distilled off the residue was dissolved in 160 ml of anhydrous dichloromethane The solution obtained The reaction mixture was refluxed for 3 h cooled to room temperature The organic layer was separated the aqueous layer was washed with 3×300 ml of methyl-tert-butyl ether The combined organic extract was dried over K2CO3 evaporated to dryness