Synthesis
The general procedure for the synthesis of morpholine-4-acetic acid hydrochloride from ethyl 2-(4-morpholinyl)acetate is as follows: ethyl 4-morpholinoacetate (1.1 g, 6.3 mmol) was added to 3M hydrochloric acid solution (35 ml) and the reaction was carried out at reflux for 2 hours. After completion of the reaction, the mixture was stirred at room temperature for 24 hours. Subsequently, the reaction solution was concentrated under reduced pressure. The obtained residue was dissolved in methanol and concentrated again under reduced pressure. The final solid product obtained was suspended in ether, separated by filtration and dried under reduced pressure to give 1.05 g of morpholine-4-acetic acid hydrochloride in 91.7% yield. The product was characterized by NMR (DMSO-d6) with chemical shifts of 3.3 (s, 4H), 3.9 (s, 4H), 4.2 (s, 2H).
References
[1] Journal of the American Chemical Society, 2017, vol. 139, # 34, p. 11895 - 11902
[2] Patent: US6352993, 2002, B1. Location in patent: Page column 13
[3] Journal of Molecular Structure, 2001, vol. 560, # 1-3, p. 261 - 273
[4] Patent: US5521179, 1996, A
[5] Bioconjugate Chemistry, 2016, vol. 27, # 1, p. 226 - 237
