反应详情

温度

0 °C

To a solution of 4-phenyl-2-[acetylthio-methyl]butyric acid (3.57 g, 14.2 mmole) in 66 mL of THF at 0° C., was added (S)-leucine, t-butyl ester (2.91 g 15.6 mmole) and 1-hydroxybenzotriazole hydrate (HOBTH2O, 2.86 g, 21.2 mmole) and N-methylmorpholine (4.29 g, 42.4 mmole). The mixture was stirred at 0° C. for 15 minutes, then 5.42 g of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide hydrochloride (EDC′HCl, 28.3 mmol) was added and the mixture stirred overnight. The solution was worked up by adding 100 mL methylene chloride and the mixture extracted with 3×50 mL of 5% sodium bicarbonate and washed with 2×50 mL of brine. The organic layer was dried over MgSO4, filtered, and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica gel eluted with methylene chloride/ethyl acetate (95/5). The product was separated as diastereomeric (R,S) and (S,S) fractions. The absolute stereochemistry of each fraction was not determined. Higher Rf material=1.78 g; lower Rf material=1.90 g.

1. stirringthe mixture stirred overnight
2. extractionthe mixture extracted with 3×50 mL of 5% sodium bicarbonate
3. washwashed with 2×50 mL of brine
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. customThe residue was purified by flash chromatography on silica gel
8. washeluted with methylene chloride/ethyl acetate (95/5)
9. customThe product was separated as diastereomeric (R,S) and (S,S) fractions