Synthesis
General procedure for the synthesis of (2S,3R)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutyric acid from (2S,3S)-2-amino-3-hydroxybutyric acid and di-tert-butyl dicarbonate:
1. di-tert-butyl dicarbonate (550 mg, 2.52 mmol) was added to a mixture of (2S,3S)-2-amino-3-hydroxybutyric acid (250 mg, 2.10 mmol) and sodium bicarbonate (529 mg, 6.30 mmol) in methanol (2.5 mL) and water (2.5 mL) at 0 °C.
2. The reaction mixture was slowly warmed to room temperature and stirred at room temperature for 18 hours.
3. Upon completion of the reaction, the methanol was removed by concentration under reduced pressure.
4. The residual aqueous phase was adjusted to pH 3~4 with 6N hydrochloric acid solution and then extracted three times with ether.
5. The organic phases were combined, washed sequentially with water and saturated brine, and then dried with anhydrous sodium sulfate.
6. The desiccant was removed by filtration, and the filtrate was concentrated under reduced pressure and dried under vacuum for 24 h. (2S,3S)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutyric acid (304 mg) was obtained as a white solid.
7. The retention time (Rt) was 0.36 min as analyzed by LCMS and mass spectrometry showed m/z 220 [M + H]+ and m/z 218 [M-H]-.
References
[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 38, p. 6935 - 6960
[2] Journal of the American Chemical Society, 2000, vol. 122, # 41, p. 10214 - 10215
[3] Journal of the American Chemical Society, 2003, vol. 125, # 7, p. 1877 - 1887
[4] Journal of Organic Chemistry, 1982, vol. 47, # 26, p. 5160 - 5167
[5] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 16, p. 4329 - 4332
