反应详情

温度

-10 °C

N-[3-(1-naphthalenyl)-2-(1-naphthalenylmethyl)-1-oxopropyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysine, 4 g (6.6 mmol), 1.58 g (6.6 mmol) of [2R-(2R*,3S*)]-3-amino-2-hydroxy-5-methylhexanoic acid, 1-methylethyl ester, monohydrochloride, and 1.79 g (13.2 mmol) of 1-hydroxybenzotriazole are combined in 80 ml of dimethylformamide. The [2R-(2R*,3S*)]-3-amino-2-hydroxy-5-methylhexanoic acid, 1-methylethyl ester, monohydrochloride is neutralized with 1.4 ml (10.1 mmol) of triethylamine. The solution is cooled to -10° C. and 1.36 g (6.6 mmol) of dicyclohexylcarbodiimide is added with stirring. The reaction mixture is kept cold for 8 hours while stirring under nitrogen, allowed to warm to room temperature overnight, filtered, the filtrate concentrated and the residue partitioned between ethyl acetate and water. The organic layer is separated and extracted with saturated solution of sodium bicarbonate, dried (sodium sulfate), filtered and concentrated. The residue is flash chromatographed over silica gel 60 (230-400 mesh), eluted with hexane-ethyl acetate (2:3), the eluates collected, dissolved in diethyl ether, filtered and the filtrate concentrated to afford 4.01 g (77%) of the title compound as a white amorphous solid.

1. stirringwhile stirring under nitrogen
2. temperatureto warm to room temperature overnight
3. filtrationfiltered
4. concentrationthe filtrate concentrated
5. customthe residue partitioned between ethyl acetate and water
6. customThe organic layer is separated
7. extractionextracted with saturated solution of sodium bicarbonate
8. dry with materialdried (sodium sulfate)
9. filtrationfiltered
10. concentrationconcentrated
11. customchromatographed over silica gel 60 (230-400 mesh)
12. washeluted with hexane-ethyl acetate (2:3)
13. customthe eluates collected
14. dissolutiondissolved in diethyl ether
15. filtrationfiltered
16. concentrationthe filtrate concentrated