4-Methylmorpholine → N-(2-Acetylthiomethyl-4-phenylbutanoyl)-(L)-Leucine t-butyl ester

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence