Ethylmorpholine → HCID 67863547, compound

Participants

Reaction Conditions

Reaction Steps

0.75 g of benzyl[(S)-1-[[[methoxy[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinyl]methyl]carbamoyl]-3-methylbutyl]carbamate was dissolved in 60 ml of methanol containing 1.4 ml of 1M hydrochloric acid. The solution was hydrogenated over 0.1 g of 10% palladium-on-charcoal for 4 hours. After filtration and evaporation, the residue was re-evaporated three times with 30 ml of toluene each time in order to remove water. The white residue obtained was dissolved in 10 ml of dimethylformamide and the solution was cooled to 0° C. 0.375 g of N-benzyloxycarbonyl-L-proline, 180 mg of N-ethylmorpholine and 0.4 g of hydroxybenzotriazole were added and, after all of the solids had dissolved, 0.345 g of N,N'-dicyclohexylcarbodiimide was added. After stirring at room temperature for 18 hours, the solvent was removed by evaporation. The residue was triturated with 30 ml of ethyl acetate and the mixture was filtered in order to remove dicyclohexylurea. The filtrate was washed twice with 30 ml of saturated sodium hydrogen carbonate solution each time, dried over anhydrous sodium sulfate and evaporated to give a colorless gum which was purified by flash chromatography on silica gel using 15% methanol in ethyl acetate for the elution. There was obtained 0.98 g of benzyl(S)-2-[[(S)-1-[[[methoxy[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinyl]methyl]carbamoyl]-3-methylbutyl]carbamoyl]-1-pyrrolidinecarboxylate in the form of a white foam.

Provenance & Evidence