Sodium Iodide → Dibenzyl (3-Succinimidopropyl)malonate

HRID 413323Notes

Reaction equation

HRID 413323 reaction equation
[H-].[Na+].[C:3]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:15])[CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].Br[CH2:25][CH2:26][CH2:27]Cl.[I-].[Na+].[C:31]1(=[O:37])[NH:35][C:34](=[O:36])[CH2:33][CH2:32]1.[K]>C1COCC1.CC(C)=O.CN(C=O)C.O>[C:34]1(=[O:36])[N:35]([CH2:25][CH2:26][CH2:27][CH:4]([C:3]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6])[C:31](=[O:37])[CH2:32][CH2:33]1

Participants

10

Reactant 5

HCID 5238Sodium IodideHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 84754Dibenzyl malonateHCID 67533854Potassium succinimide

Product 1

HCID 23298652Dibenzyl (3-Succinimidopropyl)malonateYield 23%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 4.4 g) was added to a solution of dibenzyl malonate (29.5 g) in THF (300 ml) and the mixture was stirred at room temperature for 30 min, then a solution of 1-bromo-3-chloropropane (10 ml) in THF (30 ml) was added dropwise. The solution was heated at reflux for 18 h, then cooled and evaporated in vacuo. The oily residue was dissolved in hexane (500 ml) and washed with water and brine, then dried (MgSO4) and evaporated to give a colourless oil. This oil was dissolved in acetone (300 ml) and sodium iodide (20 g) was added. The solution was stirred at room temperature for 18 h, then evaporated and the residue partitioned between water and hexane. The layers were separated and the organic layer was dried (MgSO4) and evaporated to give a pale yellow oil which was dissolved in dry DMF. Potassium succinimide (15 g) was added and the mixture was heated at 80° C. for 18 h. The mixture was cooled, poured into water (500 ml) and extracted with diethyl ether (3×200 ml). The ether layers were combined, washed with water, dried and evaporated. The residue was purified by column chromatography, eluting with diethyl ether, to give the title compound (9.65 g, 23%) as a colourless oil.

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 18 h
  3. temperaturecooled
  4. customevaporated in vacuo
  5. dissolutionThe oily residue was dissolved in hexane (500 ml)
  6. washwashed with water and brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customto give a colourless oil
  10. stirringThe solution was stirred at room temperature for 18 h
  11. customevaporated
  12. customthe residue partitioned between water and hexane
  13. customThe layers were separated
  14. dry with materialthe organic layer was dried (MgSO4)
  15. customevaporated
  16. customto give a pale yellow oil which
  17. temperaturethe mixture was heated at 80° C. for 18 h
  18. temperatureThe mixture was cooled
  19. extractionextracted with diethyl ether (3×200 ml)
  20. washwashed with water
  21. customdried
  22. customevaporated
  23. customThe residue was purified by column chromatography
  24. washeluting with diethyl ether

Sources & evidence

ORD record
ord-1779fe73ccb14f6180a4700e58e2a7e8
Source dataset
uspto-grants-2003_05
Patent number
US06566384B1

Reaction notes

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