ethyl 1,2,3,6-tetrahydropyridine-5-carboxylate;hydrochloride

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

実験手順: First 2.1 g (11 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride and then 4.53 g (35 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.32 g (10 mmol) of 3-[2-(p-toluenesulphonyloxy)ethyl]chroman in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 1.65 g (52.3%) of 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester are obtained in the form of a yellow oil. The 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from acetone/diethyl ether and melts at 177°-178°. after cooling is concentrated by evaporation under a high vacuum Water is added to the oily residue and extraction The combined organic phases are extracted with 2N hydrochloric acid while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane The combined dichloromethane phases are dried over sodium sulphate concentrated by evaporation in vacuo

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

実験手順: First 2.1 g (11 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride and then 4.53 g (35 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.32 g (10 mmol) of 3-[2-(p-toluenesulphonyloxy)ethyl]chroman in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 1.65 g (52.3%) of 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester are obtained in the form of a yellow oil. The 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from acetone/diethyl ether and melts at 177°-178°. after cooling is concentrated by evaporation under a high vacuum Water is added to the oily residue and extraction The combined organic phases are extracted with 2N hydrochloric acid while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane The combined dichloromethane phases are dried over sodium sulphate concentrated by evaporation in vacuo

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(3,3-Diphenyl-3-propen-1-yloxy)ethanol (4.0 g, 15.7 mmol) was dissolved in dry dioxan (80 ml) and stirred under an atmosphere of hydrogen for 3 h at room temperature in the presence of 10% palladium on carbon catalyst (50% aqueous paste) and then filtered. The solvent was evaporated in vacuo to give 4.0 g (100%) of 2-(3,3-diphenyl-1-propyloxy)ethanol. A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (3.9 g, 15 mmol) in dry THF (30 ml) kept under a nitrogen atmosphere was cooled to 10° C. and a solution of n-butyl-lithium in hexanes (6.0 ml, 2.5 M) was added dropwise. The reaction mixture was stirred for 1 h at room temperature and heated at reflux temperature for 1.5 h and then cooled to room temperature. p-Toluenesulphonyl chloride (2.9 g, 15 mmol) was added and the mixture was stirred at room temperature for 1.5 h. Ethyl 1,2,5,6-tetrahydro-3-pyridinecarboxylate hydrochloride (3.8 g, 20 mmol) and potassium carbonate (5.0 g, 38 mmol) were added and the mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 4 h. The reaction mixture was allowed to stand overnight and was diluted with ice water (25 ml) and ethyl acetate (100 ml). The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) and the combined aqueous extracts was washed with ethyl acetate (25 ml). The acidic aqueous phase was adjusted to pH 5 with a sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with a diluted sodium bicarbonate solution, dried (Na2SO4) and the solvent evaporated in vacuo to give 1.9 9 (32%) of the title compound as an oil. heated at reflux temperature for 1.5 h cooled to room temperature the mixture was stirred at room temperature for 1.5 h the mixture was stirred at room temperature for 0.5 h heated at reflux temperature for 4 h to stand overnight The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) the combined aqueous extracts was washed with ethyl acetate (25 ml) extracted with ethyl acetate The organic extract was washed with a diluted sodium bicarbonate solution dried (Na2SO4) the solvent evaporated in vacuo

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(3,3-Diphenyl-3-propen-1-yloxy)ethanol (4.0 g, 15.7 mmol) was dissolved in dry dioxan (80 ml) and stirred under an atmosphere of hydrogen for 3 h at room temperature in the presence of 10% palladium on carbon catalyst (50% aqueous paste) and then filtered. The solvent was evaporated in vacuo to give 4.0 g (100%) of 2-(3,3-diphenyl-1-propyloxy)ethanol. A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (3.9 g, 15 mmol) in dry THF (30 ml) kept under a nitrogen atmosphere was cooled to 10° C. and a solution of n-butyl-lithium in hexanes (6.0 ml, 2.5 M) was added dropwise. The reaction mixture was stirred for 1 h at room temperature and heated at reflux temperature for 1.5 h and then cooled to room temperature. p-Toluenesulphonyl chloride (2.9 g, 15 mmol) was added and the mixture was stirred at room temperature for 1.5 h. Ethyl 1,2,5,6-tetrahydro-3-pyridinecarboxylate hydrochloride (3.8 g, 20 mmol) and potassium carbonate (5.0 g, 38 mmol) were added and the mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 4 h. The reaction mixture was allowed to stand overnight and was diluted with ice water (25 ml) and ethyl acetate (100 ml). The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) and the combined aqueous extracts was washed with ethyl acetate (25 ml). The acidic aqueous phase was adjusted to pH 5 with a sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with a diluted sodium bicarbonate solution, dried (Na2SO4) and the solvent evaporated in vacuo to give 1.9 9 (32%) of the title compound as an oil. heated at reflux temperature for 1.5 h cooled to room temperature the mixture was stirred at room temperature for 1.5 h the mixture was stirred at room temperature for 0.5 h heated at reflux temperature for 4 h to stand overnight The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) the combined aqueous extracts was washed with ethyl acetate (25 ml) extracted with ethyl acetate The organic extract was washed with a diluted sodium bicarbonate solution dried (Na2SO4) the solvent evaporated in vacuo

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (3.9 g, 15 mmol) in dry THF (30 ml) kept under a nitrogen atmosphere was cooled to 10° C. and a solution of n-butyllithium in hexanes (6.0 ml, 2.5 M) was added dropwise. The reaction mixture was stirred for 1 h at room temperature and heated at reflux temperature for 1.5 h and then cooled to room temperature. p-Toluenesulphonyl chloride (2.9 g, 15 mmol) was added and the mixture was stirred at room temperature for 1.5 h. Ethyl 1,2,5,6-tetrahydro-3-pyridinecarboxylate hydrochloride (3.8 g, 20 mmol) and potassium carbonate (5.0 g, 38 mmol) were added and the mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 4 h. The reaction mixture was allowed to stand overnight and was diluted with ice water (25 ml) and ethyl acetate (100 ml). The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) and the combined aqueous extracts was washed with ethyl acetate (25 ml). The acidic aqueous phase was adjusted to pH 5 with a sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with a diluted sodium bicarbonate solution, dried over sodium sulphate and the solvent evaporated in vacuo to give 1.9 g (32%) of the title compound as an oil. TLC: rf=0.21 (SiO2 ; n-heptane/THF=7:3). 1H NMR (CDCl3)δ 4.12 (t, 1H); 7.00 (m, 1H). heated at reflux temperature for 1.5 h cooled to room temperature the mixture was stirred at room temperature for 1.5 h the mixture was stirred at room temperature for 0.5 h heated at reflux temperature for 4 h to stand overnight The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) the combined aqueous extracts was washed with ethyl acetate (25 ml) extracted with ethyl acetate The organic extract was washed with a diluted sodium bicarbonate solution dried over sodium sulphate the solvent evaporated in vacuo

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

実験手順: First 2.1 g (11 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride and then 4.53 g (35 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.32 g (10 mmol) of 3-[2-(p-toluenesulphonyloxy)ethyl]-chroman in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 1.65 g (52.3%) of 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester are obtained in the form of a yellow oil. The 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from acetone/diethyl ether and melts at 177°-178°. after cooling is concentrated by evaporation under a high vacuum Water is added to the oily residue and extraction The combined organic phases are extracted with 2N hydrochloric acid while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane The combined dichloromethane phases are dried over sodium sulphate concentrated by evaporation in vacuo

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

実験手順: First 2.1 g (11 mmol) of 1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride and then 4.53 g (35 mmol) of N-ethyl-N,N-diisopropylamine are added to a solution of 3.32 g (10 mmol) of 3-[2-(p-toluenesulphonyloxy)ethyl]chroman in 50 ml of absolute dimethylformamide. The mixture is stirred for 16 hours at 60° and, after cooling, is concentrated by evaporation under a high vacuum. Water is added to the oily residue and extraction is carried out with diethyl ether. The combined organic phases are extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline, while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane. The combined dichloromethane phases are dried over sodium sulphate and concentrated by evaporation in vacuo. 1.65 g (52.3%) of 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester are obtained in the form of a yellow oil. The 1-[2-(chroman-3-yl)ethyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid ethyl ester hydrochloride produced therefrom using hydrochloric acid in diethyl ether crystallises from acetone/diethyl ether and melts at 177°-178°. after cooling is concentrated by evaporation under a high vacuum Water is added to the oily residue and extraction The combined organic phases are extracted with 2N hydrochloric acid while cold, with sodium hydroxide solution (30% strength) and extracted with dichloromethane The combined dichloromethane phases are dried over sodium sulphate concentrated by evaporation in vacuo

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(3,3-Diphenyl-3-propen-1-yloxy)ethanol (4.0 g, 15.7 mmol) was dissolved in dry dioxan (80 ml) and stirred under an atmosphere of hydrogen for 3 h at room temperature in the presence of 10% palladium on carbon catalyst (50% aqueous paste) and then filtered. The solvent was evaporated in vacuo to give 4.0 g (100%) of 2-(3,3-diphenyl-1-propyloxy)ethanol. A solution of 2-(3,3-diphenyl-1-propyloxy)ethanol (3.9 g, 15 mmol) in dry THF (30 ml) kept under a nitrogen atmosphere was cooled to 10° C. and a solution of n-butyl-lithium in hexanes (6.0 ml, 2.5 M) was added dropwise. The reaction mixture was stirred for 1 h at room temperature and heated at reflux temperature for 1.5 h and then cooled to room temperature. p-Toluenesulphonyl chloride (2.9 g, 15 mmol) was added and the mixture was stirred at room temperature for 1.5 h. Ethyl 1,2,5,6-tetrahydro-3-pyridinecarboxylate hydrochloride (3.8 g, 20 mmol) and potassium carbonate (5.0 g, 38 mmol) were added and the mixture was stirred at room temperature for 0.5 h and then heated at reflux temperature for 4 h. The reaction mixture was allowed to stand overnight and was diluted with ice water (25 ml) and ethyl acetate (100 ml). The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) and the combined aqueous extracts was washed with ethyl acetate (25 ml). The acidic aqueous phase was adjusted to pH 5 with a sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with a diluted sodium bicarbonate solution, dried (Na2SO4) and the solvent evaporated in vacuo to give 1.9 9 (32%) of the title compound as an oil. heated at reflux temperature for 1.5 h cooled to room temperature the mixture was stirred at room temperature for 1.5 h the mixture was stirred at room temperature for 0.5 h heated at reflux temperature for 4 h to stand overnight The separated organic phase was extracted with a 10% citric acid solution (4×50 ml) the combined aqueous extracts was washed with ethyl acetate (25 ml) extracted with ethyl acetate The organic extract was washed with a diluted sodium bicarbonate solution dried (Na2SO4) the solvent evaporated in vacuo