Synthesis
The 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 is as follows:
1. di-tert-butyl dicarbonate (550 mg, 2.52 mmol) was added to a mixture of methanol (2.5 mL) and water (2.5 mL) containing L-isothreonine (250 mg, 2.10 mmol) and sodium bicarbonate (529 mg, 6.30 mmol) at 0 °C.
2. The reaction mixture was gradually warmed to room temperature and stirred continuously at room temperature for 18 hours.
3. Upon completion of the reaction, the methanol was removed by concentration and the remaining aqueous phase was adjusted to pH 3~4 with 6N hydrochloric acid solution.
4. The acidified aqueous phase was extracted with ether (3 times) and all organic phases were combined.
5. The organic phase was washed with water and brine sequentially, and then dried with anhydrous sodium sulfate.
6. The desiccant was removed by filtration, and the filtrate was concentrated under vacuum and further dried under vacuum for 24 h. (2R,3S)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutyric acid (304 mg) was obtained as a white solid.
Product identification: LCMS retention time (Rt) = 0.36 min; mass spectrum (MS) m/z 220 [M + H]+, 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
