(S)-3-phenylmorpholine

Synthesis

Step 3. A THF solution of (S)-5-phenylmorpholin-3-one (481 mg, dissolved in 6 mL of THF) was slowly added dropwise to a LiAlH4/THF suspension (0.47 g LiAlH4 dissolved in 2 mL of THF) at room temperature for a controlled time of over 5 minutes. After the dropwise addition, the reaction mixture was stirred at room temperature for 1 h, followed by transferring to a 72 °C oil bath for heating overnight. Upon completion of the reaction, the mixture was cooled to 0 °C and the reaction was quenched by sequential addition of H2O (0.47 mL), 3M NaOH aqueous solution (0.47 mL) and H2O (1.4 mL). The quenched mixture was diluted with Et2O (30 mL) and stirred for 10 min before separating the ether phase by filtration. The filtrate was concentrated and further dried under vacuum to give (S)-3-phenylmorpholine as a colorless solid (424 mg, 96% yield).LCMS (m/z): 164.2 (MH+), retention time 0.33 min.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 15, p. 4316 - 4320
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 20, p. 5319 - 5322
[3] Angew. Chem., 2013, vol. 125, # 20, p. 5427 - 5430,4
[4] Patent: US9242996, 2016, B2. Location in patent: Page/Page column 265; 266
[5] Patent: WO2018/116285, 2018, A1. Location in patent: Page/Page column 24