(S)-(-)-4-Isobutyloxazolidine-2,5-dione

75-44-5

61-90-5

3190-70-3

General procedure for the synthesis of (S)-4-isobutyloxazolidine-2,5-dione from phosgene and L-leucine: L-leucine amide (HO-Leu-NH2, 10.0 g, 76.2 mmol) was suspended in 150 mL of anhydrous tetrahydrofuran (THF), and heated to 50 °C. A 20% phosgene solution of toluene (76.0 mL, 152.4 mmol) was slowly added to the amino acid suspension. After about 1 hour, the amino acids were completely dissolved to form a clarified solution. The reaction solution was concentrated on a rotary evaporator, transferred to a beaker, and the product was precipitated by the addition of hexane. The white solid was separated by filtration and dissolved in toluene. The toluene solution was filtered through a bed of diatomaceous earth to remove insoluble impurities. Excess hexane was added to the filtrate to precipitate the product again. N-carboxy-L-leucine anhydride (Leu NCA) was obtained by filtration separation and dried under vacuum. 9.0 g (75% yield) of Leu NCA was finally obtained as a white crystalline solid. Its 1H NMR (d6-DMSO) data were as follows: δ 9.13 (1H), 4.44 (1H), 1.74 (1H), 1.55 (2H), 0.90 (6H) ppm.