Morpholine → Ethyl 4-morpholinepropionate

Ethyl-3-bromoproprionate (3.20 ml; 25 mmol) was added to a mixture of morpholine (2.20 ml; 25 mmol) and Na2CO3 (2.78 g; 26 mmol) in 4.5 ml of EtOH at RT. The mixture was stirred for 30 min at RT and 4 h at reflux. After cooling to RT and filtering, the filtrate was concentrated and the residue was dissolved in H2O. The pH was adjusted to ~1.5 with saturated KHSO4 and the acidic mixture was washed with Et2O. Solid K2CO3 was added to the aqueous layer until a pH of ~9 was reached. The basic mixture was extracted with CH2Cl2, dried (MgSO4) and concentrated to afford 4.75 g (100+%; contained trace solvent) of ethyl-3-morpholinoproprionate as a colorless liquid. A solution of this ester (935 mg; 5 mmol) in 20 ml of Et2O was added to a suspension of LiAlH4 (400 mg; 10 mmol) in 80 ml of Et2O at 0° C. After stirring for 30 min at 0° C., the reaction was quenched by the careful addition of 0.42 ml of H2O followed by 0.42 ml of 15% NaOH and 1.26 ml of H2O. MgSO4 was added and the suspension was filtered and concentrated to afford 531 mg (73%) of Compound 201a as a colorless liquid.

1. temperatureat reflux
2. temperatureAfter cooling to RT
3. filtrationfiltering
4. concentrationthe filtrate was concentrated
5. dissolutionthe residue was dissolved in H2O
6. washthe acidic mixture was washed with Et2O
7. additionSolid K2CO3 was added to the aqueous layer until a pH of ~9
8. extractionThe basic mixture was extracted with CH2Cl2
9. dry with materialdried (MgSO4)
10. concentrationconcentrated

ORD record

ord-0a6f9599bf9749e09996aad696db22e6

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05760036