[Synthesis]
General procedure for the synthesis of 2-((tert-butoxycarbonyl)amino)-4-(methylthio)butanoic acid from di-tert-butyl dicarbonate and DL-methionine: DL-methionine (20 g, 0.134 mol) was dissolved in 250 mL of a 10% aqueous sodium carbonate solution and cooled to 0 °C. A solution of di-tert-butyl dicarbonate (32.17 g, 0.147 mol) dissolved in 100 mL of dioxane was slowly added dropwise over a period of 1 hour. After the dropwise addition was completed, the cooling bath was removed and the reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, about half of the solvent was removed by evaporation under reduced pressure. The reaction mixture was cooled with an ice bath and the pH was adjusted to 2-3 with 10% aqueous citric acid.The aqueous phase was extracted with ethyl acetate (3 x 200 mL) and the organic layers were combined and washed sequentially with 200 mL of water and 200 mL of saturated saline (2 x 200 mL). The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was ground with mixed solvent ethyl acetate-petroleum ether at -20 °C to give the pure product 2-((tert-butoxycarbonyl)amino)-4-(methylthio)butanoic acid (28 g, 84% yield). The product was a white solid with a melting point of 88-90 °C (literature value 87-91 °C). Thin layer chromatography (TLC) Rf = 0.67 (unfolding agent S4).1H NMR (600 MHz, CDCl3) δ: 5.27 (br s, 1H, NH), 4.45 (m, 1H), 2.58 (t, J = 7.5 Hz, 2H), 2.18 (m, 1H), 2.11 (s, 3H, SCH3), 1.98 (m, 1H). 1.45 (s, 9H, t-Bu).13C NMR (150.9 MHz, CDCl3) δ: 176.91 (COOH), 155.60 (NCOO), 80.32, 52.73, 31.86, 29.93, 28.24 (3C), 15.32.IR (KBr) νmax (cm-1): 3380 ( NH), 3500-2800 (br, COOH), 1715 (C=O, acid), 1673 (C=O, carbamate), 1543 (amide II), 2977 (s), 1368 (m, CH3). High resolution mass spectrometry (HRMS-ESI) calculated value C10H19O4NNaS [M+Na]+: 272.09270, measured value: 272.09281. |