Sodium Iodide → 2-Fluoromethyl-2-phthalimido-5-iodopentanenitrile

HRID 1607761Notes

Reaction equation

HRID 1607761 reaction equation
[Na+].[I-:2].[F:3][CH2:4][C:5]([N:19]1[C:23](=[O:24])[C:22]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]2[C:20]1=[O:29])([CH2:8][CH2:9][CH2:10]OCC1C=CC=CC=1)[C:6]#[N:7].C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>CC#N.O>[F:3][CH2:4][C:5]([N:19]1[C:23](=[O:24])[C:22]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]2[C:20]1=[O:29])([CH2:8][CH2:9][CH2:10][I:2])[C:6]#[N:7]

Participants

7

Reactant 4

HCID 5238Sodium Iodide2×HCID 24477Sodium Thiosulfate2×HCID 516892Sodium Bicarbonate2×HCID 147716542-Fluoromethyl-2-phthalimido-5-benzyloxypentanenitrile

Product 1

HCID 147716572-Fluoromethyl-2-phthalimido-5-iodopentanenitrileYield 83.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

Chlorotrimethylsilyl (22 g) is added dropwise over 20 minutes to a suspension of NaI (30 g) in CH3CN (300 ml) cooled to 0° C. Stirring is continued for 30 minutes at room temperature. 2-Fluoromethyl2-phthalimido-5-benzyloxypentanenitrile (25 g) in CH3CN (50 ml) is added, and the mixture is stirred overnight at room temperature. This mixture is then poured into cold water containing sodium bicarbonate and sodium thiosulfate, and extracted with diethyl ether. The organic layer is dried over MgSO4 and concentrated in vacuo. The residue is taken up in THF (200 l) and triethylamine (7 g) is added. After stirring for 1 hour, the mixture is poured into water and extracted with diethyl ether. The organic layer is washed with H2O, dried over MgSO4, and concentrated in vacuo. The residue, a mixture of 2-fluoromethyl-2-phthalimido-5-hydroxypentanenitrile and 2-fluoromethyl-2-phthalimido-5-iodopentanenitrile is taken up in CH3CN (50 ml) and added to a solution of iodotrimethylsilyl prepared as described above from TMS Cl (22 g) and NaI (30 g) in CH3CH (300 ml). The mixture is stirred overnight at room temperature. Then it is poured into cold water containing sodium bicarbonate and sodium thiosulfate, and extracted with diethyl ether. The residue obtained after concentration of the organic layer in vacuo is filtered on a florisil column (30 g). Elution with diethyl ether and removal of the solvent under reduced pressure gives 22 g of 2-fluoromethyl-2-phthalimido-5-iodopentanenitrile as an oil.

Workup

  1. stirringthe mixture is stirred overnight at room temperature
  2. extractionextracted with diethyl ether
  3. dry with materialThe organic layer is dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. additiontriethylamine (7 g) is added
  6. stirringAfter stirring for 1 hour
  7. additionthe mixture is poured into water
  8. extractionextracted with diethyl ether
  9. washThe organic layer is washed with H2O
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated in vacuo
  12. additionThe residue, a mixture of 2-fluoromethyl-2-phthalimido-5-hydroxypentanenitrile and 2-fluoromethyl-2-phthalimido-5-iodopentanenitrile
  13. additionadded to a solution of iodotrimethylsilyl
  14. customprepared
  15. stirringThe mixture is stirred overnight at room temperature
  16. extractionextracted with diethyl ether
  17. customThe residue obtained after concentration of the organic layer in vacuo
  18. filtrationis filtered on a florisil column (30 g)
  19. washElution
  20. customwith diethyl ether and removal of the solvent under reduced pressure

Sources & evidence

ORD record
ord-a9c4087a42bd43b98e489f79265d9084
Source dataset
uspto-grants-1989_09
Patent number
US04866206

Reaction notes

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