GENERAL STEPS: Ammonium formate (3.04 g, 48.2 mmol) and 10% palladium/activated charcoal (500 mg) were added to a methanolic solution (50 mL) of (4-benzylmorpholin-2-yl)methanol (1.00 g, 4.82 mmol). The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (20 mL) and cooled in an ice bath. To this solution, di-tert-butyl dicarbonate (1.58 g, 7.23 mmol) and triethylamine (1.35 mL, 9.64 mmol) were added sequentially and the reaction mixture was stirred at room temperature for 3 hours. At the end of the reaction, the solvent was evaporated under reduced pressure, water was added to the residue and extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=5:1→1:1) to afford the target compound tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (907 mg, 87% yield) as a colorless oil.1H NMR (400 MHz, DMSO-d6) δ 1.40 (9H, s), 2.47-2.66 (1H, m), and 2.73-2.92 (1H, m), 3.25-3.45 (4H, m), 3.70 (1H, d, J=13.4 Hz), 3.79 (1H, dd, J=11.6, 2.4 Hz), 3.85 (1H, d, J=12.8 Hz), 4.77 (1H, t, J=5.5 Hz).
