反应详情

温度

-15 °C

87.6 g Boc-L-Phe-OH was dissolved in a mixture of 50 ml dimethylformamide (DMF) and 300 ml 1,2-dimethoxyethane (DME) and cooled to −15° C. Subsequently, 37 ml N-methylmorpholine (NMM) (1 equivalent) was added at once and subsequently 45 ml isobutylchloroformate (IBCF) (1 equivalent) was added dropwise over 10 min. The mixture was then stirred for further 5 min at −15° C. 40 g TFA.H-L-Pro-NH2 (1.06 equivalents) was subsequently added in portions over 5 min, and then 315 ml N,N-diisopropyl-N-ethylamine (DIEA) (1 equivalent) was added at once. The reaction mixture was reacted over night at room temperature and atmospheric pressure. Subsequently, the reaction mixture was concentrated in a rotatory evaporator equipped with a water aspirator and a dry ice/acetone trap, and the residue was taken in 1 l of ethylacetate followed by twelve washes with 80 ml 1N aqueous KHSO4 solution, one wash with 80 ml brine, ten washes with 80 ml saturated aqueous NaHCO3 solution, one wash with 80 ml brine in a 2 l separatory funnel. The subsequent drying was carried out over 50 g Na2SO4. After filtration through a sinter glass funnel (coarse porosity) was concentrated as described above. The residue of evaporation (dry foam) was then triturated in 1 l hexane, and a solid was collected on a sinter glass funnel (120 mm i.d.×120 mm, medium porosity). This was followed by drying in a desiccator over 12 hours at room temperature and a pressure of 0.1 to 1 mm Hg (vacuum oil pump, with dry ice/acetone trap). Thus, 92.8 g Boc-L-Phe-L-Pro-NH2 was obtained (yield: 77.8%).

1. additionwas added dropwise over 10 min
2. customThe reaction mixture was reacted over night at room temperature
3. concentrationSubsequently, the reaction mixture was concentrated in a rotatory evaporator
4. customequipped with a water aspirator and a dry ice/acetone trap
5. washwash with 80 ml brine, ten washes with 80 ml saturated aqueous NaHCO3 solution, one
6. washwash with 80 ml brine in a 2 l separatory funnel
7. customThe subsequent drying
8. filtrationAfter filtration through a sinter glass funnel (coarse porosity)
9. concentrationwas concentrated
10. customThe residue of evaporation (dry foam)
11. customwas then triturated in 1 l hexane
12. customa solid was collected on a sinter glass funnel (120 mm i.d.×120 mm, medium porosity)
13. customby drying in a desiccator over 12 hours at room temperature