Water → HCID 23009178, compound

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).

1. customPurification by silica gel chromatography
2. washeluting with 92:8 dichloromethane/methanol (DCM/MeOH)
3. customgave
4. custompurified tert-butyl ethyl[3-(4-morpholinyl)propyl]carbamate (1.4 g)
5. extractionThe product was extracted into EA
6. extractionthe EA extract
7. washwashed with brine
8. dry with materialdried over magnesium sulfate
9. customRemoval of the EA

ORD record

ord-b0e9b2c97fff4dc49c3045ca9219faaa

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129396B2