Ethyl chloroacetate → (5S)-5-cyclopropylmorpholin-3-one

To a cold, stirred suspension of sodium hydride (600 mg, 14.99 mmol) in toluene (20 mL) was added dropwise a solution of (S)-2-amino-2-cyclopropylethanol (680 mg, 6.72 mmol)) in toluene (12 mL). The reaction mixture was then allowed to warm to room temperature and a solution of ethyl chloroacetate (824 mg, 6.72 mmol) in toluene (4 mL) was added dropwise. The resulting mixture was stirred for 3 h at room temperature. The mixture was then quenched with the addition of 10 mL of 1N aq. hydrochloric acid and concentrated under vacuum. The residue was diluted with THF, dried with magnesium sulfate, concentrated under vacuum and filtered through a pad of silica gel, flushing with additional THF. The resulting filtrate was concentrated under vacuum, and the residue was further purified by flash chromatography (ISCO, 12 g silica gel column, using a 0-100% ethyl acetate in n-heptane gradient as the eluent to afford 208 mg of (S)-5-cyclopropylmorpholin-3-one as a white solid (MS: (M+H)+=142.2).

1. stirringThe resulting mixture was stirred for 3 h at room temperature
2. customThe mixture was then quenched with the addition of 10 mL of 1N aq. hydrochloric acid
3. concentrationconcentrated under vacuum
4. additionThe residue was diluted with THF
5. dry with materialdried with magnesium sulfate
6. concentrationconcentrated under vacuum
7. filtrationfiltered through a pad of silica gel
8. customflushing with additional THF
9. concentrationThe resulting filtrate was concentrated under vacuum
10. customthe residue was further purified by flash chromatography (ISCO, 12 g silica gel column

ORD record

ord-a4eca5776f324ce8801e418d483a4f8b

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697739B2