GENERAL STEPS: To a 1000 mL round bottom flask was added (3R)-thiomorpholine-3-carboxylic acid hydrochloride (10.0 g, 0.054 mol), di-tert-butyl dicarbonate (13.0 g, 0.060 mol), sodium bicarbonate (45.0 g, 0.536 mol), and methanol (500 mL). The mixture was stirred at room temperature for 24 hours. Upon completion of the reaction, methanol was removed by distillation under reduced pressure. The residue was dissolved in water and washed three times with ether. Subsequently, the pH of the aqueous phase was adjusted to 2 with saturated potassium bisulfate solution and extracted with dichloromethane three times. The organic phases were combined, washed 3 times with saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate/acetic acid) to afford 8.63 g of white solid product in 64.6% yield. The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3) and EI-MS: 1H-NMR δ 5.33 (1H, d, J = 90.4 Hz), 4.39 (1H, br m), 3.30 (2H, br m), 2.95 (1H, m), 2.71 (1H, m), 2.53 (1H, m), 1.53 (9H, s) ; EI-MS m/z: 247.1 [M]+.
