Dicyclohexylcarbodiimide → [(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]-4-methylpentyl](phthalimidomethyl)phosphinic acid methyl ester

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Reaction Steps

3.0 g of 2(RS)-[[(RS)-(methoxy)(phthalimidomethyl)phosphinyl]methyl]-4-methylvaleric acid were dissolved in 50 ml of tetrahydrofuran and 1.65 g of L-leucine N-methylamide and 2.2 g of hydroxybenzotriazole were added while stirring. After all of the solids had dissolved, 2.02 g of N,N'-dicyclohexylcarbodiimide were added and the mixture was stirred at room temperature overnight. The tetrahydrofuran was removed by evaporation, the residue was triturated with 100 ml of ethyl acetate and the mixture was filtered in order to remove dicyclohexylurea. The filtrate was washed twice with 50 ml of saturated sodium hydrogen carbonate solution each time, dried over anhydrous sodium sulfate and evaporated to give a yellow gum. This gum was purified by flash chromatography on silica gel using 5% methanol in ethyl acetate for the elution. There were obtained 3.32 g of [(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]-4-methylpentyl](phthalimidomethyl)phosphinic acid methyl ester in the form of a white foam.

Provenance & Evidence