Sodium hydride → ethyl N-[(4-phthalimidobutyl)oxy]acetimidate

HRID 1418112Notes

Reaction equation

HRID 1418112 reaction equation
[H-].[Na+].[OH:3][N:4]=[C:5]([O:7][CH2:8][CH3:9])[CH3:6].Br[CH2:11][CH2:12][CH2:13][CH2:14][N:15]1[C:19](=[O:20])[C:18]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:17]2[C:16]1=[O:25].C(=N)([O-])C.[Cl-].[NH4+]>O1CCCC1.CO.C(OCC)(=O)C.C(Cl)(Cl)Cl>[C:16]1(=[O:25])[N:15]([CH2:14][CH2:13][CH2:12][CH2:11][O:3][N:4]=[C:5]([O:7][CH2:8][CH3:9])[CH3:6])[C:19](=[O:20])[C:18]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:17]12

Participants

10

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 93575N-(4-Bromobutyl)phthalimideHCID 99894Ethyl acetohydroximateHCID 21947001Acetimidate

Product 1

HCID 54518438ethyl N-[(4-phthalimidobutyl)oxy]acetimidateYield 71.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a dried 100 mL 3-necked round-bottom flask equipped with an addition funnel and gas inlet was added sodium hydride (1.55 g, 39 mmol, 60% oil dispersion). The sodium hydride was washed three times with 10 mL portions of hexane and covered with 30 mL of dry tetrahydrofuran. The flask was placed over a magnetic stirrer, flushed with a slow stream of nitrogen, and stirred vigorously while ethyl N-hydroxyacetimidate (3.65 g, 35 mmol) (Aldrich Chemical Co., Milwaukee, Wis.) was added rapidly dropwise. After addition was complete and gas evolution had subsided, the suspension was heated at reflux for 18 hours. Upon cooling, the suspension was stirred while N-(4-bromobutyl)-phthalimide (10.0 g, 35 mmol) (Aldrich Chemical Co., Milwaukee, Wis.) in 30 ml of dry tetrahydrofuran (THF) was added rapidly dropwise. After addition was complete, the reaction mixture was refluxed for 48 hours under nitrogen. Thin-layer chromatography (TLC) of the crude reaction mixture in 95:5 chloroform:ethyl acetate showed conversion of the acetimidate into a product with Rf =0.45. The reaction suspension was treated with methanol (15 mL), and then with saturated aqueous ammonium chloride (50 mL). The organic solvents were removed on a rotary evaporator and the residue was transferred to a separatory funnel and partitioned between ethyl acetate and water. After three extractions with 100 mL portions of ethyl acetate, the combined layers were washed with brine, dried over magnesium sulfate and evaporated to yield a light yellow oil. Column chromatography on silica-gel (95:5 chloroform:ethyl acetate) yielded 7.8 g (25 mmol, 71%) of ethyl N-[(4-phthalimidobutyl)oxy]acetimidate (1) as a colorless oil. Single spot on TLC with Rf =0.45 (visualized with a hand-held ultraviolet lamp with output at about 280 nm). 1H NMR: δ7.7 (s, 4H), 3.8 (m, 4H), 3.6 (t, 2H), 1.8 (s, 3H), 1.6 (m, 4H), 1.1 (s, 3H).

Workup

  1. customTo a dried 100 mL 3-necked round-bottom flask equipped with an addition funnel and gas inlet
  2. washThe sodium hydride was washed three times with 10 mL portions of hexane
  3. customThe flask was placed over a magnetic stirrer
  4. customflushed with a slow stream of nitrogen
  5. additionwas added rapidly dropwise
  6. additionAfter addition
  7. temperaturethe suspension was heated
  8. temperatureat reflux for 18 hours
  9. temperatureUpon cooling
  10. additionwas added rapidly dropwise
  11. additionAfter addition
  12. temperaturethe reaction mixture was refluxed for 48 hours under nitrogen
  13. customThe organic solvents were removed on a rotary evaporator
  14. customthe residue was transferred to a separatory funnel
  15. custompartitioned between ethyl acetate and water
  16. extractionAfter three extractions with 100 mL portions of ethyl acetate
  17. washthe combined layers were washed with brine
  18. dry with materialdried over magnesium sulfate
  19. customevaporated
  20. customto yield a light yellow oil

Sources & evidence

ORD record
ord-6824350a66a04c88880ca452d0da5ffe
Source dataset
uspto-grants-1999_03
Patent number
US05880270

Reaction notes

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