反应详情

Fmoc-Met-OSu was prepared in situ by the reaction of Fmoc-Met-OH (14.87 g), HOSu (5.52 g) and DCC (8.26 g) in THF (tetrahydrofuran, 200 ml) at 0° C. for 3.5 hours. Precipitated dicyclohexylurea (DCU) was removed by filtration and the THF filtrate was added to a cold solution of H-Asp(OtBu)-OH in 220 ml of 10:1 water/THF to which had been added 40 ml of 1N sodium hydroxide. After stirring the reaction mixture at room temperature overnight, solid citric acid (20 g) was added along with ethyl acetate (600 ml). The ethyl acetate layer was separated, washed with 10% citric acid and brine, then dried (MgSO4). Evaporation of the ethyl acetate solution gave a residue which was dissolved in ethyl acetate (200 ml) and treated with DCHA (7.84 ml) to precipitate 17.93 g of the DCHA salt of the title compound, mp 159°-162° C.

1. customPrecipitated dicyclohexylurea (DCU) was removed by filtration
2. additionthe THF filtrate was added to a cold solution of H-Asp(OtBu)-OH in 220 ml of 10:1 water/THF to which
3. additionhad been added 40 ml of 1N sodium hydroxide
4. additionwas added along with ethyl acetate (600 ml)
5. customThe ethyl acetate layer was separated
6. washwashed with 10% citric acid and brine
7. dry with materialdried (MgSO4)
8. customEvaporation of the ethyl acetate solution
9. customgave a residue which
10. customto precipitate 17.93 g of the DCHA salt of the title compound, mp 159°-162° C.