In a round-bottomed flask, triethylamine (188 g, 1.86 mol, 1.0 eq.) was slowly added dropwise to a stirred mixed solution containing di-tert-butyl dicarbonate (162 g, 0.744 mol, 1.2 eq.) and L-glutamic acid-5-methyl ester (100 g, 0.62 mol, 1.0 eq.) in a solvent consisting of a mixture of water (500 mL) and 1,4-dioxane (500 mL) in a solvent mixture of water (500 mL) and 1,4-dioxane (500 mL). The reaction mixture was stirred continuously for 18 hours at room temperature. Upon completion of the reaction, the reaction solution was extracted with methyl tert-butyl ether (MTBE, 500 mL x 2). The aqueous phase was cooled in an ice bath and the pH was carefully adjusted to 3 by slowly adding 10% citric acid solution.Subsequently, the carbamate product in the aqueous phase was extracted with ethyl acetate (500 mL × 2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford (S)-2-((tert-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid (Compound A4-2) as a clear viscous oil (180 g, 100% yield). Mass spectrometry (MS-ESI) analysis showed [M + 1]+ m/z 262.1.
