4-Methylmorpholine → HCID 178445920, compound

Participants

Reaction Conditions

Reaction Steps

70 mg. (0.2 mmole) of N-benzyloxycarbonyl-3-(1-naphthyl)-L-alanine and 40 mg. (0.22 mmole) of N-hydroxy-5-norbornene-2,3-dicarboximide were dissolved in 2 ml. of methylene chloride. The solution was cooled to 0° C., and there were then added 50 mg. (0.24 mmole) of dichlorohexylcarbodiimide; the mixture was stirred at 0° C. for 1 hour. The resulting solution was added to a cooled solution prepared from 5 ml. of a dimethylformamide solution of 123 mg. (0.2 ml.) of 3-(1-naphthyl)-L-alanyl-L-histidyl-L-leucinol dihydrobromide by neutralization with 20 mg. (0.2 mmole) of N-methylmorpholine. The mixture was stirred overnight at room temperature. The dicyclohexylurea precipitated was removed by filtration, and the filtrate was concentrated by evaporation under reduced pressure. To the residue was added a 5% w/v aqueous solution of sodium bicarbonate, and the oily substance thus formed was extracted with ethyl acetate. The organic layer was washed successively with water and with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulphate and concentrated by evaporation under reduced pressure. When a small amount of water was added to the residual syrup, it solidified and was separated by filtration. This product (143 mg) was then purified by silica gel column chromatography (eluent: chloroform/methanol 10:1 by volume) to afford 55 mg. of the desired compound as a white powdery solid, melting at 199°-200° C.; [α]24 -81.6° (C=0.5, methanol).

Provenance & Evidence