反应详情

In a 3 neck, 3 L flask equipped with a mechanical stirrer is placed 17.25 g (26 mmol) Fmoc-Arg(Pmc) and 300 mL acetonitrile and the mixture is stirred at ambient temperature until a clear solution is obtained. Benzotriazolyloxy-tris[pyrrolidino]-phosphonium hexafluoroacetate (PyBOP) is added, the solution cooled to 2° C., and 2.6 g (26 mmol) of N-methylmorpholine is added, forming a white tar. Dimethylformamide (52 mL) is added slowly until the tar dissolves, and the mixture is stirred at 3° C. for 30 minutes. A solution of HCl.Val-Asp(OAllyl)-OBzl) (10.4 g, 26 mmol) in 39 mL of dimethylformamide is added over 20 minutes at 2-3° C., followed by N-methylmorpholine (7.5 mL) to attain pH 7. Cooling is ceased, and the mixture is stirred for 2.5 hours. The mixture is then diluted with 250 mL water and 250 mL ethyl acetate. The ethyl acetate layer is removed and washed with water (2×100 mL) and brine (2×100 mL) and concentrated to afford a white solid which is crystallized from 175 mL ethyl acetate to give 18.5 g Fmoc-Arg(Pmc)-Val-Asp(OAllyl)-OBzl (95A %). The ethyl acetate filtrate is concentrated and the gummy residue triturated with ethyl acetate to afford an additional 3.12 g of product. (Mcalc 1007; M+1obsvd 1008).

1. customIn a 3 neck, 3 L flask equipped with a mechanical stirrer
2. customis obtained
3. temperaturethe solution cooled to 2° C.
4. customforming a white tar
5. dissolutiondissolves
6. stirringthe mixture is stirred at 3° C. for 30 minutes
7. temperatureCooling
8. stirringthe mixture is stirred for 2.5 hours
9. customThe ethyl acetate layer is removed
10. washwashed with water (2×100 mL) and brine (2×100 mL)
11. concentrationconcentrated
12. customto afford a white solid which
13. customis crystallized from 175 mL ethyl acetate