[Synthesis]
General procedure for the synthesis of (R)-2-((tert-butoxycarbonyl)amino)-4-hydroxybutyric acid from D-homoserine and di-tert-butyl dicarbonate: 1N NaOH (7.5 mL) was added to an ethanol-water (2:1, 21 mL) solution of D-homoserine (0.9 g, 7.5 mmol, 1 eq.), followed by di-tert-butyl dicarbonate (1.81 g, 8.3 mmol, 1.1 equiv) and THF (7 mL). The reaction mixture was stirred at room temperature for 16 hours. After the reaction was completed, the reaction mixture was extracted with diethyl ether (2 x 30 mL). The aqueous layer was cooled to 0 °C, acidified to pH 2 with 1N HCl and extracted with ethyl acetate (4 × 30 mL). The organic layers were combined and dried with Na2SO4. The solvent was concentrated under reduced pressure and the crude product was purified by column chromatography (cyclohexane/ethyl acetate, 1:1) to afford (R)-2-((tert-butoxycarbonyl)amino)-4-hydroxybutyric acid (3a) as a colorless oil. Yield: 1.35 g (6.1 mmol, 81%).1H NMR (300 MHz, D2O): δ = 1.38 (s, 9H, tert-butyl-CH3), 1.83-1.67 (m, 1H, 3-CH), 2.05-1.87 (m, 1H, 3-CH), 3.68-3.54 (m, 2H, 4-CH2), 3.97 ( dd, J = 4.7, 9.2 Hz, 1H, 2-CH).13C NMR (75 MHz, D2O): δ = 27.6 (tert-butyl-C), 33.8 (3-C), 52.7 (2-C), 58.3 (4-C), 81.0 (tert-butoxy-C), 157.6 (carbonyl-C), 179.0 (carboxy-C).HRMS ( ESI+, MeOH): m/z = 242.1002 [M + Na]+ (calculated value C9H17NO5Na+: 242.0999). |