N-(2,3-Epoxypropyl)phthalimide → 3-Aminopropyl(2-hydroxy-3-phthalimido-propyl)phosphinic acid

HRID 729169Notes

Reaction equation

HRID 729169 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][P:5]([OH:7])[OH:6].[I-].[O:9]1[CH2:23][CH:10]1[CH2:11][N:12]1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2[C:13]1=[O:22]>C[Si](C)(C)N[Si](C)(C)C.Cl>[NH2:1][CH2:2][CH2:3][CH2:4][P:5]([CH2:23][CH:10]([OH:9])[CH2:11][N:12]1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2[C:13]1=[O:22])(=[O:7])[OH:6]

Participants

6

Reactant 3

HCID 21601N-(2,3-Epoxypropyl)phthalimideHCID 30165Iodide IonHCID 99892683-Amino-propanephosphonous

Product 1

HCID 99018533-Aminopropyl(2-hydroxy-3-phthalimido-propyl)phosphinic acid

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 13838HexamethyldisilazaneSolvent

Procedure

A suspension of 2.46 g of 3-aminopropylphosphonous acid in 20 ml of hexamethyldisilazane is heated to reflux under an inert atmosphere for 24 hours after which a clear solution results. The excess hexamethyldisilazane is removed by distillation at atmospheric pressure under a slight positive pressure of inert gas to afford a colourless oil. The oil is cooled to circa 66° and treated with 0.64 g of anhydrouszinc iodide and 4.62 g of N-(2,3-epoxypropyl)phthalimide. An exothermic reaction occurs. The reaction mixture is refluxed for 6 hours after which time thin layer chromatography indicates the reaction to be complete. The reaction mixture is filtered and the filtrate evaporated to dryness in vacuo at 40°. The residue is dissolved in water and stirred at roomtemperature for 1 hour and the water removed in vacuo to give an oily solid. This is dissolved in 25 ml of 2.0M aqueous hydrochloric acid and washed with dichloromethane and ether. Removal of the water at 40° in vacuo affords a brown solid which is purified by ion-exchange chromatography on DOWEX® 50 W ×8 (14-40 mesh) to give 3-aminopropyl(2-hydroxy-3-phthalimido-propyl) phosphinic acid, m.p. 268°-71°, as a white solid.

Workup

  1. temperatureis heated
  2. temperatureto reflux under an inert atmosphere for 24 hours after which a clear solution
  3. customresults
  4. customThe excess hexamethyldisilazane is removed by distillation at atmospheric pressure under a slight positive pressure of inert gas
  5. customto afford a colourless oil
  6. temperatureThe oil is cooled to circa 66°
  7. customAn exothermic reaction
  8. temperatureThe reaction mixture is refluxed for 6 hours after which time thin layer chromatography
  9. customthe reaction
  10. filtrationThe reaction mixture is filtered
  11. customthe filtrate evaporated to dryness in vacuo at 40°
  12. dissolutionThe residue is dissolved in water
  13. customthe water removed in vacuo
  14. customto give an oily solid
  15. washwashed with dichloromethane and ether
  16. customRemoval of the water at 40° in vacuo
  17. customaffords a brown solid which
  18. customis purified by ion-exchange chromatography on DOWEX® 50 W ×8 (14-40 mesh)

Sources & evidence

ORD record
ord-871d695d43464b4a930a074dd4cff022
Source dataset
uspto-grants-1991_09
Patent number
US05051524

Reaction notes

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