Synthesis
[Step 1] Synthesis of (R)-2-((tert-butoxycarbonyl)amino)butanoic acid
Di-tert-butyl dicarbonate (4.7 g, 21 mmol) was slowly added to a mixed solution of (R)-2-aminobutyric acid (2.0 g, 19 mmol) and sodium bicarbonate (1.6 g, 19 mmol) in a mixture of 1,4-dioxane and water (3:10 v/v/v, total 26 mL) under ice bath cooling. The reaction mixture was stirred at room temperature for 120 hours and then concentrated under reduced pressure. The resulting crude product was dissolved in chloroform, to which 1N hydrochloric acid was subsequently added and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 2.0 g (quantitative yield) of the title compound (hereinafter referred to as Reference Example Compound 27).
References
[1] Patent: EP2832724, 2015, A1. Location in patent: Paragraph 0169
[2] European Journal of Organic Chemistry, 2002, # 23, p. 3995 - 4004
[3] Journal of the American Chemical Society, 1997, vol. 119, # 4, p. 656 - 673
[4] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 22, p. 3237 - 3242
[5] Tetrahedron, 2006, vol. 62, # 42, p. 9966 - 9972
