General procedure for the synthesis of N-benzyl-3-hydroxymethylmorpholine from 4-benzyl-5-oxo-3-morpholinecarboxylic acid: triethylamine (7.29 g, 10.0 mL, 72 mmol) was added to a solution of intermediate 58 (17.7 g, 75.3 mmol) in tetrahydrofuran (THF, 300 mL). The reaction system was cooled to 0 °C and the borane dimethyl sulfide complex (~10 M solution of THF, 45 mL, 450 mmol) was slowly added. Subsequently, the reaction mixture was heated to reflux for 16 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and the excess borane was carefully destroyed. The excess THF was evaporated under reduced pressure and the residue was adjusted to strong basicity with 2 M NaOH solution (250 mL) and subsequently extracted with ethyl acetate (EtOAc, 3 x 150 mL). The aqueous phase was acidified to pH 1 with concentrated hydrochloric acid and extracted again. The combined organic phases were washed with brine (150 mL), dried over anhydrous magnesium sulfate (MgSO4), and concentrated under reduced pressure to give N-benzyl-3-hydroxymethylmorpholine (13.5 g, 87% yield) as a clear oil.1H NMR (CDCl3) δ: 7.29-7.16 (5H, m), 4.05 (1H, d, J = 12.8 Hz), 3.88 (1H dd, J = 11.5, 4.5 Hz), 3.78 (1H, m), 3.70-3.53 (2H, m), 3.51-3.40 (2H, m), 3.20 (1H, d, J = 13.2 Hz), 2.68 (1H, dt, J = 12.1, 2.8 Hz), 2.48 (1H, m), 2.27 (1H, m). 2.20-2.15 (1H, bs).
