Morpholine → 3-(Morpholin-4-yl)-1,2,5,6-tetrahydropyridin-2-one

A solution of 3-chloro-5,6-dihydro-1H-pyridin-2-one (44, 1.0 g, 7.6 mmol) in THF (4 mL) was treated with morpholine (663 mg, 0.67 mL, 7.6 mmol, 1.0 equiv) and triethylamine (TEA, 1.54 g, 2.1 mL, 15.2 mmol, 2.0 equiv) at room temperature, and the resulting reaction mixture was warmed up to reflux for 6 h. When HPLC and TLC showed the reaction was deemed complete, the reaction mixture was quenched with water (10 mL) and EtOAc (20 mL), and the resulting mixture was stirred at room temperature for 10 min. The two layers were separated, and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (5 mL), dried over MgSO4, and concentrated in vacuo. The residue was then purified by flash column chromatography (SiO2, 15–40% EtOAc/hexane gradient elution) to afford the desired 3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (45, 595 mg, 1.384 g theoretical, 43%) as pale-yellow oil, which solidified upon standing at room temperature in vacuo and was found to be essentially pure to do the following reaction without further purification. For 45, CIMS m/z 181 (M+−H, C9H14N2O2).

1. customthe resulting reaction mixture
2. temperaturewas warmed up
3. temperatureto reflux for 6 h
4. customthe reaction mixture was quenched with water (10 mL) and EtOAc (20 mL)
5. customThe two layers were separated
6. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
7. washThe combined organic extracts were washed with saturated NaCl aqueous solution (5 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe residue was then purified by flash column chromatography (SiO2, 15–40% EtOAc/hexane gradient elution)

ORD record

ord-d57079d1b2ed488c85e5fb34062555bf

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07153960B2