L-Aspartic Acid → N-[(3S)-Tetrahydro-2,5-dioxo-3-furanyl]formamide

온도

50 °C

13.3 g (0.1 mole) of L-aspartic acid was added to the mixture of 6.0 g of formic acid and 20.6 g of acetic anhydride, and the mixture was stirred for 4 hours at 50° C. After cooling the reaction mixture to 20° C., the crystal of N-formyl-L-aspartic anhydride precipitated was isolated by filtration, and washed with 30 ml of ethylether. After drying, 10.8 g (0.075 moles) of N-formyl-L-aspartic anhydride were obtained. The crystal thus obtained was admixed with 75 ml of acetic acid to form a slurry, to which 700 ml of toluene containing 16.4 g (0.07 moles) of D-valine-N-(S)-ethylbenzylamide was added over a period of 40 minutes while stirring at 15° C., and the mixture was stirred for further 1 hour at 60° C. Quantitative analysis using HPLC indicated that 0.044 moles of N-formyl-α-L-aspartyl-D-valine-N-(S)-ethylbenzylamide (yield of 62.9% based on D-valine-N-(S)-ethylbenzylamide) were produced in the reaction mixture. 1000 ml of 0.5N hydrochloric acid was added to the reaction mixture, which was then heated under reflux for 20 minutes. The toluene layer was subjected to layer separation to isolate the aqueous layer, which was cooled to 40° C. and then adjusted to pH 5 with 15% sodium carbonate. After stirring for 5 hours at 10° C., the crystal precipitated was isolated by filtration and dried to obtain 11.65 g (0.0333 moles) of α-L-aspartyl-D-valine-N-(S)-ethylbenzylamide. Yield: 47.6% based on D-valine-N-(S)-ethylbenzylamide.