3-Morpholinone

To a solution of ethanolamine (197 mmol, 1.1 equiv) in i-PrOH (100 mL) was portionwise added small pieces ofsodium (197 mmol, 1.1 equiv). The mixture was heated at 50 °C for 5 h, and the resulting yellow solution was cooled in an ice-water bath. Ethyl chloroacetate (179 mmol, 1.0equiv) was dropwise added at 0 °C, and the resulting yellow suspension was heated at 80 °C for 2 h. Insoluble materials were removed by paper filtration and washed with i-PrOH. The combined filtrate and washings were concentrated in vacuo, and the resulting brown solids were recrystallized from iPrOH/EtOAc to afford 3-morpholinone in 52percent yield.Under nitrogen, Na (45.26 g, 1.97 mol)Was added in portions to a mixed solution of dioxane and isopropanol, and the temperature was raised to 50 ° C to promote the dissolution of Na(Na dissolves very slowly, generally takes 4 to 5 hours).After all the Na is dissolved, Dropping amino ethanol (98ml, 1.67mo) 1, drop Bi, 50 ° C stirring 30 ~ 40min.Was transferred to cold water, controlled at -10 ° C, and ethyl chloroacetate (182 ml, 1.75mo 1) was added dropwise. Drop 10 ° C stirring 30 ~ 40min.Gradually heated to 80 ° C, the reaction about 10h, finished, hot filter, the filtrate evaporated to dry yellow oily liquid, dissolved with ethyl acetate, standing, the above clear ethyl acetate layer out of cooling crystallization, To be precipitated after the white needle-like crystals after filtration, to obtain moles of crude ketone. The remaining yellow oil was recrystallized again as described above in a yield of 36percentunder a nitrogen atmosphere, sodium hydride (60 wt percent, 1.2 g) and a solution of dioxane (25 ml) was cooled to 0 °C, ethanolamine (1.5 ml) was added at room temperature and stirred for 30 minutes. This reaction liquid is cooled to 0 °C, after 30 minutes stirring at room temperature ethyl chloroacetate (2.7 ml) was added, this reaction mixture was further stirred and heated for 40 minutes under reflux condition. After cooling the reaction liquid, solid is removed by filtration. Under a reduced pressure by concentrating somas, refining residues is obtained in column chromatography (ethyl acetate: methanol = 19:1), obtained as a colorless solid morpholin-3-one (500 mg).Under an argon atmosphere, to a solution of 2-chloro-N-(2-hydroxyethyl)acetamide (3.2 g, 23 mmol) in tetrahydrofuran (64 ml) was added sodium hydride (1.2 g, 30 mmol) under ice-cooling, and the mixture was stirred for 1 hr. Then, the mixture was stirred at room temperature for 1 hr, and further at 60° C. for 4 hr. After cooling, water (540 μl) was added, and the reaction mixture was dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (232 mg, yield 10percent).

Molecular Weight:101.10
XLogP3:-0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:101.047678466
Monoisotopic Mass:101.047678466
Topological Polar Surface Area:38.3
Heavy Atom Count:7
Complexity:81.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes