Phthalimide → 2-[2-(Hexyloxy)ethoxy]ethanamine

HRID 1384789Notes

Reaction equation

HRID 1384789 reaction equation
[CH2:1]([O:7][CH2:8][CH2:9][OH:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[H-].[Na+].Br[CH2:14][CH2:15][N:16]1C(=O)C2=CC=CC=C2C1=O.C1(=O)C2C(=CC=CC=2)C(=O)N1.O.NN>CN(C=O)C.CCO>[CH2:15]([NH2:16])[CH2:14][O:10][CH2:9][CH2:8][O:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

8

Reactant 5

HCID 6809PhthalimideHCID 81702-HexyloxyethanolHCID 113251H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)-HCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydride

Product 1

HCID 211836482-[2-(Hexyloxy)ethoxy]ethanamineYield 50%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of ethylene glycol mono-n-hexyl ether (15.0 g, 0.1 mol) and sodium hydride (0.1 mol) was dissolved in dry DMF (150 mL). After the mixture was stirred for 1-2 hours, N-(2-bromoethyl)phthalimide (25.4 g, 0.1 mol) was added with continued stirring and the mixture was warmed on a steam bath for 8 h. The DMF was then removed by evaporation and the residue dissolved in hot toluene, and the solution was concentrated to remove solvent. The residue was purified using silica gel chromatography using ethyl acetate to give 25 g (78%). 1H NMR (CDCl3, TMS): δ 0.87 (t, 3H, J=6.8Hz), 1.24˜1.30 (m, 8H), 1.56˜1.60 (m, 2H), 3.47 (t, 3H, J=6.8 Hz), 3.72 (dd, 2H, J1=4.4 Hz, J2=5.6 Hz), 4.06 (t, 3H, J=9.6 Hz), 4.41˜4.46 (m, 4H) 7.50˜7.52 (m, 2H), 7.72˜7.76 (m, 2H). A solution of the thus-derived isoindoledione and hydrazine hydrate (5.5 g, 0.11 mol) in EtOH (200 mL) was heated at reflux for 8 hours. The precipitate (phthalhydrazide) was removed by filtration, and the filtrate was concentrated to low volume and refiltered. The filtrate was then concentrated to dryness, treated with water (20 mL) and sodium hydroxide (11 g), and extracted with methylene chloride (4×100 mL). The combined organic layers are dried over MgSO4, concentrated, and purified by silica gel to provide 7 g of the amine product (50%). 1H-NMR (CDCl3, TMS): δ 0.89 (t, 3H, J=6.8 Hz), 1.29˜1.36 (m, 6H), 1.55˜1.60 (m, 2H), 2.03 (m, 2H), 3.45˜3.49 (m, 4H), 3.53˜3.55 (m, 2H), 3.71˜3.74 (m, 2H).

Workup

  1. stirringwith continued stirring
  2. temperaturethe mixture was warmed on a steam bath for 8 h
  3. customThe DMF was then removed by evaporation
  4. dissolutionthe residue dissolved in hot toluene
  5. concentrationthe solution was concentrated
  6. customto remove solvent
  7. customThe residue was purified
  8. customto give 25 g (78%)
  9. temperatureat reflux for 8 hours
  10. customThe precipitate (phthalhydrazide) was removed by filtration
  11. concentrationthe filtrate was concentrated to low volume
  12. concentrationThe filtrate was then concentrated to dryness
  13. additiontreated with water (20 mL) and sodium hydroxide (11 g)
  14. extractionextracted with methylene chloride (4×100 mL)
  15. dry with materialThe combined organic layers are dried over MgSO4
  16. concentrationconcentrated
  17. custompurified by silica gel

Sources & evidence

ORD record
ord-9db7158cf0254afb8f846610f69115f0
Source dataset
uspto-grants-2001_07
Patent number
US06262029B1

Reaction notes

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