1093192-07-4

General procedure for the synthesis of (S)-2-amino-3-tert-butoxycarbonylamino-3-methyl-3-methylbutanoic acid methyl ester from (S)-3-((tert-butoxycarbonyl)amino)-3-methyl-2-(((S)-1-phenylethyl)amino)butanoic acid methyl ester: Methyl (S)-3-((tert-butoxycarbonyl)amino)-3-methyl-2-(((S)-1-phenylethyl)amino)butanoate ( 135, 0.50 g, 1.4 mmol) was dissolved in anhydrous tetrahydrofuran (THF, 10 mL). The solution was transferred to a 50 mL flask and operated under argon protection. Palladium hydroxide catalyst (0.18 g, 20 wt%) was quickly weighed and added to the reaction flask. Subsequently, the atmosphere in the flask was replaced with hydrogen and the hydrogen pressure (-101 kPa) was maintained. After the reaction was carried out for 2 h, the completion of the reaction was confirmed by LC/MS analysis. The reaction mixture was filtered through a diatomaceous earth pad and the filtrate was concentrated to dryness. The residue was purified by the CombiFlash system (eluent: dichloromethane solution of 0-5% methanol) to afford the target product (S)-methyl (S)-2-amino-3-tert-butyloxycarbonylamino-3-methylbutanoate (34) as a white solid (330 mg, 95% yield). The product was characterized by 1H NMR (300 MHz, CDCl3) and 13C NMR (75 MHz, CDCl3) and the data were consistent with the expected structure.

[1] Patent: WO2012/31298, 2012, A2. Location in patent: Page/Page column 121-122
[2] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 2, p. 94 - 102
[3] Patent: WO2008/154642, 2008, A2. Location in patent: Page/Page column 245-246