Phthaloyl chloride → 2-Fluoromethyl-2-phthalimido-5-benzyloxypentanenitrile

HRID 1607756Notes

Reaction equation

HRID 1607756 reaction equation
[F:1][CH2:2][C:3]([NH2:17])([CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:4]#[N:5].C(N(CC)CC)C.[C:25](Cl)(=[O:35])[C:26]1[C:27](=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:28](Cl)=[O:29].C1(=O)NC(=O)C2=CC=CC1=C2>ClCCl>[F:1][CH2:2][C:3]([N:17]1[C:28](=[O:29])[C:27]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]2[C:25]1=[O:35])([CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:4]#[N:5]

Participants

6

Reactant 4

HCID 6955Phthaloyl chlorideHCID 8471Triethylamine2×HCID 147716532-Fluoromethyl-2-amino-5-benzyloxypentanenitrileHCID 18926764Isophthalimide

Product 1

HCID 147716542-Fluoromethyl-2-phthalimido-5-benzyloxypentanenitrileYield 47.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of 2-fluoromethyl-2-amino-5-benzyloxypentanenitrile (74.8 g), triethylamine (100 g), and dry dichloromethane (450 ml), cooled in an ice bath, a solution of phthaloyldichloride (58 g) in dichloromethane (300 ml) is added slowly. Stirring is continued at room temperature overnight. The mixture is extracted with 2N HCl (2×750 ml), washed with water (2×750 ml), dried carefully (Na2SO4), evaporated to give a brown oil which, according to NMR analysis, contains some iso-phthalimide. The oil is dissolved in dry dichloromethane (500 ml), triethylamine (100 g) is added, and the mixture is refluxed for 3 hours. Work-up as described above gives an oil which is purified by flash-chromatography on silica (2 kg, petroleum ether/ethyl acetate 4:1). Crystallization from ether gives 2-fluoromethyl-2-phthalimido-5-benzyloxypentanenitrile (49.4 g).

Workup

  1. extractionThe mixture is extracted with 2N HCl (2×750 ml)
  2. washwashed with water (2×750 ml)
  3. dry with materialdried carefully (Na2SO4)
  4. customevaporated
  5. customto give a brown oil which
  6. temperaturethe mixture is refluxed for 3 hours
  7. customabove gives an oil which
  8. customis purified by flash-chromatography on silica (2 kg, petroleum ether/ethyl acetate 4:1)
  9. customCrystallization from ether

Sources & evidence

ORD record
ord-6cc83b3b6d404afe9977045acb2e9fce
Source dataset
uspto-grants-1989_09
Patent number
US04866206

Reaction notes

Loading…