Synthesis
Step 2. Synthesis of (S)-2-((tert-butoxycarbonyl)amino)-3-cyclohexylpropionic acid. (S)-2-amino-3-cyclohexylpropanoic acid hydrochloride (118 g, 0.57 mol) was dissolved in 0.5 N NaOH aqueous solution (1200 mL), followed by the addition of a solution of tetrahydrofuran (THF, 600 mL) of di-tert-butyl dicarbonate (Boc2O, 137 g, 0.63 mol). The reaction mixture was stirred for 2 hours. After completion of the reaction, the organic solvent was removed under reduced pressure. The aqueous phase was washed with ether (Et2O, 2 x 400 mL) to remove unreacted feedstock. Subsequently, the aqueous phase was acidified to pH 5 with aqueous 2 N HCl. The acidified aqueous phase was extracted with ethyl acetate (EtOAc, 3 × 400 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give the title compound (S)-2-((tert-butoxycarbonyl)amino)-3-cyclohexylpropanoic acid (142 g, 92%) as an oil.1H NMR (CDCl3) δ: 0.92 (m, 1H), 1.09-1.30 (m, 3H), 1.48 (s, 9H), 1.51 (m, 1H), 1.52 (m, 1H), 1.66 (m, 5H), 1.78 (m, 1H), 4.32 (m, 1H), 4.88 (m, 1H), 8.55-9.48 (br s, 1H).
References
[1] Journal of Antibiotics, 1996, vol. 49, # 9, p. 909 - 920
[2] Patent: WO2007/117557, 2007, A2. Location in patent: Page/Page column 91
[3] Patent: US5756763, 1998, A
