Synthesis
[Step 1] Synthesis of methyl (R)-2-((tert-butoxycarbonyl)amino)-3-hydroxypropionate: To a solution of methanol (50 mL) containing methyl (R)-2-amino-3-hydroxypropionate (3.0 g, 19 mmol) and triethylamine (8.1 mL, 58 mmol) was slowly added di-tert-butyl dicarbonate (4.6 g, 21 mmol). The reaction mixture was stirred at room temperature for 14 h. The reaction was terminated by the addition of dilute hydrochloric acid. After continued stirring for 1 h, the reaction mixture was diluted with the addition of water and subsequently extracted with ethyl acetate. The organic layers were combined, washed sequentially with saturated aqueous sodium bicarbonate and pure water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography (eluent ratio: hexane/ethyl acetate=20:1→2:1) to afford 4.1 g (97% yield) of the title compound ((R)-2-((tert-butoxycarbonyl)amino)-3-hydroxypropanoic acid methyl ester, hereinafter referred to as Reference Example compound 35).
References
[1] Patent: EP2832724, 2015, A1. Location in patent: Paragraph 0186
[2] Tetrahedron Letters, 1995, vol. 36, # 39, p. 7031 - 7034
[3] Patent: WO2013/110643, 2013, A1. Location in patent: Paragraph 00104; 00105
[4] Tetrahedron, 1996, vol. 52, # 36, p. 11673 - 11694
[5] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 3, p. 923 - 928
