1,2,3,4-tetrahydroquinolin-2-ylmethanol

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: Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. The reaction mixture was filtered the filtrate concentrated under reduced pressure

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

実験手順: Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. quenched by water Volatiles were removed under reduced pressure the residue dissolved in ethyl acetate washed with water and saturated aqueous sodium chloride dried over sodium sulfate concentrated under reduced pressure Fractions containing product concentrated under reduced pressure

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

実験手順: In 120 ml of ethanol, 6 g of methyl quinaldinate was reduced by hydrogen in the presence of 400 mg of platinum oxide to give 6.8 g of methyl 1,2,3,4-tetrahydroquinaldinate as an oil. 3.0 g of the resulting methylester was further reduced in a dry ether by 1 g of lithium aluminum hydride to give 2.6 g of 1,2,3,4-tetrahydro-2-quinolinemethanol. A mixture of 1.6 g of the resulting alcohol, 0.93 ml of dimethylsulfonic acid, 2.16 g of calcium carbonate and 8 ml of water was stirred at room temperature for 6 hours. To the reaction mixture was added ether and insolubles were removed by filtration. The organic portion was separated, washed with water and dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the organic portion was purified by silica gel column chromatography (eluent: chloroform) to give 1.4 g of 1-methyl-1,2,3,4-tetrahydro-2-quinolinemethanol as a pale yellow oil. were removed by filtration The organic portion was separated washed with water dried over anhydrous sodium sulfate After removal of the solvent under reduced pressure the organic portion was purified by silica gel column chromatography (eluent: chloroform)

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

実験手順: Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. The reaction mixture was filtered the filtrate concentrated under reduced pressure

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

実験手順: Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. quenched by water Volatiles were removed under reduced pressure the residue dissolved in ethyl acetate washed with water and saturated aqueous sodium chloride dried over sodium sulfate concentrated under reduced pressure Fractions containing product concentrated under reduced pressure

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

実験手順: To a solution of 2-hydroxymethyltetrahydroquinoline (35.9 g, 0.22 mol), imidazole (35.95 g, 0.528 mol), and triphenylphosphine (69.24 g, 0.264 mol) in a mixed solvent of 5:1 toluene/acetonitrile (750 mL) was added iodine (61.42 g, 0.242 mol) at 0° C. The mixture was stirred for 15 min at 0° C. and for 30 min at room temperature. Aqueous sodium thiosulfate solution (200 mL) was added. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated. The residue was triturated with diethyl ether and the insoluble materials were removed by filtration. The filtrate was concentrated and the residual oil was dissolved in DMF (200 mL). To the solution was added sodium cyanide (43.2 g, 0.881 mol) and the mixture was heated at 80° C. for 10 h. The resulting mixture was poured into ice-water and extracted with a mixture of toluene and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography with 1:1 hexane/dichloromethane to 100% dichloromethane as eluents to give 31.6 g of the title compound (94%). The organic layer was separated washed with brine dried over magnesium sulfate concentrated The residue was triturated with diethyl ether the insoluble materials were removed by filtration The filtrate was concentrated the residual oil was dissolved in DMF (200 mL) the mixture was heated at 80° C. for 10 h extracted with a mixture of toluene and ethyl acetate The organic layer was washed with brine dried over magnesium sulfate concentrated The residue was purified by silica gel column chromatography with 1:1 hexane/dichloromethane to 100% dichloromethane as eluents

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

実験手順: To a solution of 2-hydroxymethyltetrahydroquinoline (35.9 g, 0.22 mol), imidazole (35.95 g, 0.528 mol), and triphenylphosphine (69.24 g, 0.264 mol) in a mixed solvent of 5:1 toluene/acetonitrile (750 mL) was added iodine (61.42 g, 0.242 mol) at 0° C. The mixture was stirred for 15 min at 0° C. and for 30 min at room temperature. Aqueous sodium thiosulfate solution (200 mL) was added. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated. The residue was triturated with diethyl ether and the insoluble materials were removed by filtration. The filtrate was concentrated and the residual oil was dissolved in DMF (200 mL). To the solution was added sodium cyanide (43.2 g, 0.881 mol) and the mixture was heated at 80° C. for 10 h. The resulting mixture was poured into ice-water and extracted with a mixture of toluene and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography with 1:1 hexane/dichloromethane to 100% dichloromethane as eluents to give 31.6 g of the title compound (94%). The organic layer was separated washed with brine dried over magnesium sulfate concentrated The residue was triturated with diethyl ether the insoluble materials were removed by filtration The filtrate was concentrated the residual oil was dissolved in DMF (200 mL) the mixture was heated at 80° C. for 10 h extracted with a mixture of toluene and ethyl acetate The organic layer was washed with brine dried over magnesium sulfate concentrated The residue was purified by silica gel column chromatography with 1:1 hexane/dichloromethane to 100% dichloromethane as eluents

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

実験手順: To a suspension of LiAlH4 (8.3 g, 0.22 mol) in THF (200 mL) was added dropwise 2-methoxycarbonyltetrahydroquinoline (42 g, 0.22 mol) in THF (200 mL) at 0° C. The mixture was stirred for 3 h at room temperature and refluxed for 0.5 h. The excess reagent was decomposed by addition of aqueous sodium hydroxide in THF. To the mixture was added 1N aqueous NaOH, water, and diethyl ether, successively. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated to give 38.4 g of 2-hydroxymethyltetrahydroquinoline (quant). refluxed for 0.5 h The organic layer was separated washed with brine dried over magnesium sulfate concentrated

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

実験手順: Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. The reaction mixture was filtered the filtrate concentrated under reduced pressure

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

実験手順: Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound. quenched by water Volatiles were removed under reduced pressure the residue dissolved in ethyl acetate washed with water and saturated aqueous sodium chloride dried over sodium sulfate concentrated under reduced pressure Fractions containing product concentrated under reduced pressure

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

実験手順: To a solution of 2-hydroxymethyltetrahydroquinoline (7.86 g, 48.16 mmol) in dichloromethane (80 mL) containing triethylamine (10 mL, 72.23 mmol) was added trimethylsilyl chloride (6.7 mL, 52.97 mmol) at 0° C. The mixture was stirred for 10 min at 0° C. followed by addition of triethylamine (10 mL) and ethyl chlorooxalate (5.9 mL, 52.97 mmol). The mixture was stirred for 30 min at 0° C. and water was added. The organic layer was separated, washed with water, dried over magnesium sulfate, and concentrated to give 15.6 g of N-ethoxalyl-2-trimethylsilyloxymethyltetrahydroquinoline (106%): 1H NMR (270 MHz, CDCl3) δ6.97~7.16 (m, 4H), 4.68 (m, 1H), 4.09 (q, 2H, J=7 Hz), 3.72 (m, 1H), 3.54 (m, 1H), 2.65 (m, 2H), 2.37 (m, 1H), 1.69 (m, 1H), 1.06 (t, 3H, J=7 Hz), 0.03 (s, 9H). The mixture was stirred for 30 min at 0° C. The organic layer was separated washed with water dried over magnesium sulfate concentrated