N-ethyl-3-morpholin-4-ylpropan-1-amine

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

実験手順: 3-(4-Morpholinyl)propan-1-amine (35.0 g, 243 mmol) was dissolved in tetrahydrofuran (THF, 250 mL), di-tert-butyl dicarbonate (58.0 g, 266 mmol) and N,N-diisopropylethylamine (DIPEA, 84 mL, 484 mmol) were added, and the solution was stirred overnight. The solvent was removed and the residue partitioned between ethyl acetate (EA) and 1.2M hydrochloric acid (300 mL). The pH was raised to 7 with saturated aqueous sodium bicarbonate and the layers separated. The aqueous layer was extracted twice with EA (150 mL each), and the EA layers were combined, washed with brine, and dried over magnesium sulfate. The solvent was removed, giving tert-butyl 3-(4-morpholinyl)propylcarbamate (39 g). Tent-butyl 3-(4-morpholinyl)propylcarbamate (3.5 g, 14.3 mmol) was dissolved in THF (30 mL), and sodium hydride (60% dispersion in mineral oil, 1.03 g, 25.8 mmol) was added in portions. After stirring for 5 min, ethyl iodide (13.4 g, 86.0 mmol) was added and the mixture was heated to 60° C. for 7 hr then stirred at room temperature overnight. Water (5 mL) was added and the solvent removed. The residue was dissolved in EA, and the solution was washed with brine, dried over magnesium sulfate, and the solvent removed to give crude tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (2.5 g). Purification by silica gel chromatography eluting with 92:8 dichloromethane/methanol (DCM/MeOH) gave purified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (1.4 g). Purified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (350 mg, 1.3 mmol) was dissolved in 4.0M hydrogen chloride in dioxane (5 mL, 20 mmol) and stirred for 45 min. Water was added and the solution made basic with 2M aqueous sodium hydroxide. The product was extracted into EA, and the EA extract washed with brine and dried over magnesium sulfate. Removal of the EA gave N-ethyl-3-(4-morpholinyl)propan-1-amine (50 mg). Purification by silica gel chromatography eluting with 92:8 dichloromethane/methanol (DCM/MeOH) gave purified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (1.4 g) The product was extracted into EA the EA extract washed with brine dried over magnesium sulfate Removal of the EA

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

実験手順: 3-(4-Morpholinyl)propan-1-amine (35.0 g, 243 mmol) was dissolved in tetrahydrofuran (THF, 250 mL), di-tert-butyl dicarbonate (58.0 g, 266 mmol) and N,N-diisopropylethylamine (DIPEA, 84 mL, 484 mmol) were added, and the solution was stirred overnight. The solvent was removed and the residue partitioned between ethyl acetate (EA) and 1.2M hydrochloric acid (300 mL). The pH was raised to 7 with saturated aqueous sodium bicarbonate and the layers separated. The aqueous layer was extracted twice with EA (150 mL each), and the EA layers were combined, washed with brine, and dried over magnesium sulfate. The solvent was removed, giving tert-butyl 3-(4-morpholinyl)propylcarbamate (39 g). Tent-butyl 3-(4-morpholinyl)propylcarbamate (3.5 g, 14.3 mmol) was dissolved in THF (30 mL), and sodium hydride (60% dispersion in mineral oil, 1.03 g, 25.8 mmol) was added in portions. After stirring for 5 min, ethyl iodide (13.4 g, 86.0 mmol) was added and the mixture was heated to 60° C. for 7 hr then stirred at room temperature overnight. Water (5 mL) was added and the solvent removed. The residue was dissolved in EA, and the solution was washed with brine, dried over magnesium sulfate, and the solvent removed to give crude tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (2.5 g). Purification by silica gel chromatography eluting with 92:8 dichloromethane/methanol (DCM/MeOH) gave purified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (1.4 g). Purified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (350 mg, 1.3 mmol) was dissolved in 4.0M hydrogen chloride in dioxane (5 mL, 20 mmol) and stirred for 45 min. Water was added and the solution made basic with 2M aqueous sodium hydroxide. The product was extracted into EA, and the EA extract washed with brine and dried over magnesium sulfate. Removal of the EA gave N-ethyl-3-(4-morpholinyl)propan-1-amine (50 mg). Purification by silica gel chromatography eluting with 92:8 dichloromethane/methanol (DCM/MeOH) gave purified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (1.4 g) The product was extracted into EA the EA extract washed with brine dried over magnesium sulfate Removal of the EA