反应详情

温度

0 °C

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).

1. additionthere were then added 50 mg
2. additionThe resulting solution was added to a cooled solution
3. customprepared from 5 ml
4. stirringThe mixture was stirred overnight at room temperature
5. customThe dicyclohexylurea precipitated
6. customwas removed by filtration
7. concentrationthe filtrate was concentrated by evaporation under reduced pressure
8. additionTo the residue was added a 5% w/v aqueous solution of sodium bicarbonate
9. customthe oily substance thus formed
10. extractionwas extracted with ethyl acetate
11. washThe organic layer was washed successively with water and with a saturated aqueous solution of sodium chloride
12. dry with materialdried over anhydrous sodium sulphate
13. concentrationconcentrated by evaporation under reduced pressure
14. additionWhen a small amount of water was added to the residual syrup, it
15. customwas separated by filtration
16. customThis product (143 mg) was then purified by silica gel column chromatography (eluent: chloroform/methanol 10:1 by volume)
17. customto afford 55 mg