Trifluoroacetic acid → HCID 14308358, compound

Temperature

-15 °C

44 g Boc-Gly-OH (1 equivalent) was dissolved in a mixture of 50 ml DMF and 300 ml DME and subsequently cooled to −15° C. 28 ml NMM (1 equivalent) was added at once, followed by the dropwise addition of 34 ml IBCF (1 equivalent) over 10 min. The mixture was stirred a further 5 min at −15° C. 94.5 g TFA.H-L-Phe-L-Pro-NH2 (1.06 equivalents) were added in portions thereto over 5 min, followed by the addition of 44 ml DIEA (1 equivalent). 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 1.2 l ethyl acetate, followed by five washes with 80 ml 1N aqueous KHSO4 solution, five washes with 80 ml saturated aqueous NaHCO3 solution, and 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) concentration was carried out as described above. The residue of evaporation (sticky oil) was then triturated in a mixture of 1 l diethyl ether and 2 l hexane and a solid was collected on a sinter glass funnel (180 mm i.d.×180 mm, medium porosity). The subsequent drying was carried out 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). Accordingly, 100 g Boc-Gly-L-Phe-L-Pro-NH2 was obtained (yield: 94.7%).

1. additionfollowed by the dropwise addition of 34 ml IBCF (1 equivalent) over 10 min
2. waitover 5 min
3. customThe reaction mixture was reacted over night at room temperature
4. concentrationSubsequently, the reaction mixture was concentrated in a rotatory evaporator
5. customequipped with a water aspirator and a dry ice/acetone trap
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. concentrationconcentration
10. customThe residue of evaporation (sticky oil)
11. customwas then triturated in a mixture of 1 l diethyl ether and 2 l hexane
12. customa solid was collected on a sinter glass funnel (180 mm i.d.×180 mm, medium porosity)
13. customThe subsequent drying
14. waitwas carried out in a desiccator over 12 hours at room temperature

ORD record

ord-d74aa4e478834b70b38ccb7d9c7405bd

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07129213B2