Step L (1): synthesis of tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate. To a solution of tetrahydrofuran (THF, 120 mL) of 4-(tert-butoxycarbonyl)morpholine-3-carboxylic acid (4.7 g, 20.35 mmol) was added sequentially Hunig base (6.6 g, 50.875 mmol) and ethyl chloroformate (2.65 g, 24.4 mmol) at 0 °C. The reaction mixture was stirred at 0 °C to room temperature for 1.5 h. Sodium borohydride (NaBH4, 3.1 g, 81.4 mmol) was added. after 15 min, methanol (MeOH, 20 mL) was slowly added. The reaction mixture was continued to be stirred for 1 h at room temperature. Subsequently, THF and MeOH were removed under reduced pressure and diluted by adding ethyl acetate (600 mL). The organic phase was washed sequentially with saturated sodium bicarbonate (NaHCO3) solution and water, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. 3.56 g of the target product tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylate was obtained in 81% yield. The product was characterized by 1H NMR (CDCl3, 500 MHz): δ 1.46 (9H, s), 2.03 (1H, br s), 3.17 (1H, m), 3.46 (1H, m), 3.56 (1H, m), 3.72-3.86 (4H, m), 3.91 (1H, d, J = 10 Hz), 3.99 (1H, br s).
