162537-11-3

20859-02-3

79-22-1

162537-11-3

Step 1: Synthesis of (S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid: (S)-2-amino-3,3-dimethylbutanoic acid (5.0 g, 38.6 mmol) was dissolved in a mixture of dioxane (20 ml) and 2N sodium hydroxide solution (62 ml, pH=8-9) at 0 °C. Methyl chloroformate (5.88 ml, 76.33 mmol) was added dropwise with stirring. The reaction mixture was warmed up to 60°C with continuous stirring for 18 hours. After completion of the reaction, the mixture was cooled to room temperature and extracted with dichloromethane (DCM) to separate the aqueous layer. The aqueous layer was acidified to acidity with 1N hydrochloric acid and then extracted with ethyl acetate (EtOAc). The organic layer was dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to remove the solvent. The resulting crude product was stirred and distilled in hexane to give N-methoxycarbonyl-L-tert-leucine as a white solid. Yield: 8.5 g (quantitative yield). NMR hydrogen spectrum (300MHz, CDCl3): δ5.25 (d, 1H, J=10.5Hz), 4.19 (d, 1H, J=9.6Hz), 3.70 (s, 3H), 1.03 (s, 9H). Mass spectrum: [M-1]- 188 (100%). IR spectrum (potassium bromide pressed, cm-1): 3379, 2974, 1727, 1688, 1546, 1466, 1332, 1263, 1211, 1070, 1034, 1018, 843, 696.