Perfluoropropyl iodide → Boc-Val-Pro-Val-CF2CF2CF3

HRID 613237

Reaction equation

HRID 613237 reaction equation
[F:1][C:2](I)([F:10])[C:3]([F:9])([F:8])[C:4]([F:7])([F:6])[F:5].[NH:12]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C@H:13]([C:17]([N:19]1[CH2:34][CH2:33][CH2:32][C@H:20]1[C:21]([NH:23][C@H:24]([C:28](OC)=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])=[O:18])[CH:14]([CH3:16])[CH3:15]>C(OCC)C>[NH:12]([C:35]([O:37][C:38]([CH3:41])([CH3:39])[CH3:40])=[O:36])[C@H:13]([C:17]([N:19]1[CH2:34][CH2:33][CH2:32][C@H:20]1[C:21]([NH:23][C@H:24]([C:28]([C:2]([C:3]([C:4]([F:7])([F:6])[F:5])([F:9])[F:8])([F:10])[F:1])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])=[O:18])[CH:14]([CH3:16])[CH3:15]

Participants

4

Reactant 2

HCID 33977Perfluoropropyl iodideHCID 131721522Boc-Val-Pro-Val-OCH3

Product 1

HCID 131721521Boc-Val-Pro-Val-CF2CF2CF3

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  1. customto a -78° C.
  2. customan internal reaction temperature below -70° C
  3. customremove the cold bath
  4. stirringcontinue stirring for 5 minutes
  5. additionPour the reaction mixture into H2O (100 mL)
  6. extractionExtract the aqueous phase with additional diethyl ether (100 mL)
  7. dry with materialdry (MgSO4) the combined ethereal extracts
  8. customRemove the solvent in vacuo
  9. custompurify the resultant yellow foam
  10. washby flash chromatography (4.0×25 cm column eluted with 3:1 Et2O-hexane)

Sources & evidence

ORD record
ord-46f1e2beefda4f3fa9f001770ab16d54
Source dataset
uspto-grants-1999_12
Patent number
US06008196

Linked notes

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