Synthesis
General procedure for the synthesis of Z-D-tert-butylglutamic acid from benzyl chloroformate and D-glutamic acid-5-tert-butyl ester: (R)-2-amino-5-(tert-butoxy)-5-oxopentanoic acid (1.00 g, 4.92 mmol) was suspended in a solvent mixture of THF (18.45 mL) and water (6.15 mL) and was cooled to 0 °C under ice bath conditions. Benzyl chloroformate (0.773 mL, 5.41 mmol) was added slowly and dropwise to the cooled suspension, followed by stirring the reaction mixture for 2.5 hours at 0 °C. Upon completion of the reaction, the reaction mixture was diluted with 50 mL of ethyl acetate and acidified with aqueous 1 N hydrochloric acid to pH 3. The aqueous phase was extracted three times with ethyl acetate, and the organic phases were combined, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product as a clear oil. The crude product was purified by silica gel column chromatography with a gradient of eluent from 100% hexane to 100% ethyl acetate to afford the target product (R)-2-((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid as a colorless oil (1.41 g, 71% yield). The product was characterized by 1H NMR (400 MHz, chloroform-d), δ 7.44-7.29 (m, 5H), 5.53 (d, J = 7.5 Hz, 1H), 5.13 (s, 2H), 4.41 (d, J = 5.1 Hz, 1H), 2.56-2.30 (m, 2H), 2.21 (dd, J = 13.5, 6.5 Hz, 1H) , 2.06-1.88 (m, 2H), 1.45 (s, 9H).
