Synthesis
General steps:
1. suspend (R)-3-aminobutyric acid (2.415 g, 23.42 mmol) in a solvent mixture of dioxane (15 mL) and water (15.00 mL) at room temperature with stirring.
2. Triethylamine (TEA, 4.90 mL, 35.1 mmol) was added dropwise to the suspension to give a light brown solution.
3. The reaction mixture was cooled to 0 °C and di-tert-butyl dicarbonate (4.69 g, 26.9 mmol) was added in one portion.
4. The reaction mixture was stirred at room temperature for 16 hours. 5.
5. Upon completion of the reaction, the mixture was partitioned between water (80 mL) and ethyl acetate (EtOAc, 80 mL).
6. The aqueous layer was separated and washed with EtOAc.
7. The aqueous layer was acidified to pH=3 with 1 M aqueous KHSO4 and extracted with EtOAc (2 x 80 mL).
8. The EtOAc extracts were combined, washed with saturated aqueous NaCl (2 x 80 mL), dried over anhydrous Na2SO4, filtered and concentrated.
9. (R)-3-((tert-butoxycarbonyl)amino)butyric acid (4.301 g, 21.16 mmol, 90% yield) was obtained as a pale yellow solid.
10. The product was characterized by XH NMR (400 MHz, CDCl3): δ 4.92 (s, 1H), 4.14-3.96 (m, 2H), 2.56 (d, J=5.2 Hz, 2H), 1.45 (s, 9H), 1.25 (d, J=6.9 Hz, 3H).
References
[1] Patent: WO2012/125622, 2012, A1. Location in patent: Page/Page column 135-136
[2] Chinese Chemical Letters, 2015, vol. 26, # 1, p. 103 - 107
[3] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 5, p. 1421 - 1425
[4] Angewandte Chemie - International Edition, 2018, vol. 57, # 31, p. 9707 - 9710
[5] Angew. Chem., 2018, vol. 130, # 31, p. 9855 - 9858,4
