Reaktion #700419

Reaktionsgleichung

perfluoropropyl iodide

Boc-Val-Pro-Val-OCH3

→

title compound

Boc-Val-Pro-Val-CF2CF2CF3

Lösungsmittel

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto a -78° C.
2. 2
   Sonstigean internal reaction temperature below -70° C
3. 3
   Sonstigeremove the cold bath
4. 4
   workup.STIRRINGcontinue stirring for 5 minutes
5. 5
   workup.ADDITIONPour the reaction mixture into H2O (100 mL)
6. 6
   ExtraktionExtract the aqueous phase with additional diethyl ether (100 mL)
7. 7
   Trocknendry (MgSO4) the combined ethereal extracts
8. 8
   SonstigeRemove the solvent in vacuo
9. 9
   Sonstigepurify the resultant yellow foam
10. 10
    Waschenby flash chromatography (4.0×25 cm column eluted with 3:1 Et2O-hexane)

Vorschrift

Add perfluoropropyl iodide (6.6 mL, 48.0 mmol, from Aldrich, stabilized with Cu) dropwise, under N2, to a -78° C. solution of Boc-Val-Pro-Val-OCH3 ] (3.89, 9.0 mmol) in anhydrous diethyl ether (100 mL). Add methyllithium-lithium bromide complex (28.5 mL, 42.0 mmol) at a rate which maintains an internal reaction temperature below -70° C. Stir the reaction mixture at -78° C. for 1 hour, then remove the cold bath and continue stirring for 5 minutes. Pour the reaction mixture into H2O (100 mL) and acidify the aqueous phase with 1N HCl. Extract the aqueous phase with additional diethyl ether (100 mL) and dry (MgSO4) the combined ethereal extracts. Remove the solvent in vacuo and purify the resultant yellow foam by flash chromatography (4.0×25 cm column eluted with 3:1 Et2O-hexane) to yield the title compound as a white foam. (Yield: 654 mg, 13%). FT-IR (KBr) 3423, 3292, 2972, 2937, 2879, 2823, 2771, 2739, 2253, 1755, 1687, 1635, 1525, 1444, 1392, 1367, 1348, 1313, 1232, 1178, 1126, 1041, 1018, 966, 922, 910, 877, 837, 798, 756, 736, 667, 650, 632, 596 cm-1 ; 1H NMR (300 MHz, CDCl3)δ 7.63 (d, 1H, J=8.2 Hz, NH), 5.44 (d, 1H, J=9.2 Hz, NH), 5.02 (dd, 1H, J=7.8, 4.5 Hz, CH of Val), 4.64 (dd, 1H, J=8.0, 3.0 Hz, CH of Pro), 4.30 (dd, 1H, J=9.2, 6.8 Hz, α-CH of Val), 3.80-3.74 and 3.66-3.60 (pr m, 2H, CH2N), 2.31-1.92 (series of m, 6H, β-CH of Val, CH2CH2), 1.44 (s, 9H, t-Bu), 1.02 (d, 3H, J=7.0 Hz, CH3), 0.98,(d, 3H, J=6.9 Hz, CH3), 0.94 (d, 3H, J=6.7 Hz, CH3), 0.88 (d, 3H, J=6.9 Hz, CH3); 13C NMRδ 193.3, 193.0, 192.7, 172.9, 171.1, 155.7, 118.7, 115.8, 111.3, 108.9, 108.6, 108.2, 105.9, 79.6, 77.3, 77.2, 76.9, 76.6, 59.7, 59.3, 56.8, 47.8, 31.4, 29.0, 28.3, 26.9, 25.1, 19.9, 19.8, 19.7, 19.5, 19.4, 17.5, 17.4, 16.3, 16.1; 19F NMR (376.3 MHz, CDCl3)δ -80.91 (t, CF3), -119.03 and -120.43 (AB quartet, J=297 Hz, CF2), -126.62 (s, CF2), MS (CI/CH4) m/z (rel. intensity) 566 (MH+, 100). HRMS (C23H34F7N3O5) (M+) calcd 566.2492, obsd 566.2475.

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