N-Hydroxyphthalimide → HCID 68536180, compound

HRID 1187391Notes

Reaction equation

HRID 1187391 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:20][N:21]1[C:25](=[O:26])[C:24]2=[CH:27][CH:28]=[CH:29][CH:30]=[C:23]2[C:22]1=[O:31].[CH2:32]([C:36]1[N:37]([CH2:49][CH2:50][CH2:51][CH2:52]O)[C:38]2[C:47]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[N:41]=[CH:40][C:39]=2[N:48]=1)[CH2:33][CH2:34][CH3:35].N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH2:32]([C:36]1[N:37]([CH2:49][CH2:50][CH2:51][CH2:52][O:20][N:21]2[C:22](=[O:31])[C:23]3[C:24](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]2=[O:26])[C:38]2[C:47]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[N:41]=[CH:40][C:39]=2[N:48]=1)[CH2:33][CH2:34][CH3:35]

Participants

6

Reactant 4

HCID 10665N-Hydroxyphthalimide3×HCID 11776Triphenylphosphine3×HCID 75555Diisopropyl diazene-1,2-dicarboxylate3×HCID 57455399HCID 57455399, compound

Product 1

HCID 68536180HCID 68536180, compoundYield 36.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Triphenylphosphine (21.2 g, 80.7 mmol) and N-hydroxyphthalimide (13.2 g, 80.7 nmuol) were added to a solution of 4-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butan-1-ol (16.0 g, 53.8 mmol) in tetrahydrofuran (200 mL). The mixture was stirred for five minutes and then was cooled to approximately 0° C. Diisopropyl azodicarboxylate (19.6 g, 96.8 mmol) was added dropwise, and the reaction was allowed to warm to room temperature and stirred for three hours. An analysis by LC/MS indicated the presence of starting material, and the reaction was stirred at 60° C. overnight. An analysis by LC/MS indicated the presence of starting material, and additional triphenylphosphine, N-hydroxyphthalimide, and diisopropyl azodicarboxylate (26.9 mmol of each) were added to the reaction mixture. The reaction was stirred at room temperature for two hours and heated at reflux for three hours. The reaction was concentrated under reduced pressure, and the residue was dissolved in chloroform (200 mL). The resulting solution was washed with brine (3×150 mL), dried over magnesium sulfate, filtered through a layer of CELITE filter aid, and concentrated under reduced pressure. An analysis of the crude product mixture by LC/MS indicated that starting material was still present. The mixture was dissolved in tetrahydroiiran (200 mL) and treated with triphenylphosphine (21.2 g, 80.7 mmol), N-hydroxyphthalimide (13.2 g, 80.7 mmol), and diisopropyl azodicarboxylate (19.6 g, 96.8 mmol) as described above. The reaction was stirred overnight at room temperature. The product was present as a white precipitate, which was isolated by filtration and washed with tetrahydrofuran to provide 8.68 g of 2-[4-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butoxy]-1H-isoindole-1,3(2H)-dione as a white solid.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for three hours
  3. stirringthe reaction was stirred at 60° C. overnight
  4. additionwere added to the reaction mixture
  5. stirringThe reaction was stirred at room temperature for two hours
  6. temperatureheated
  7. temperatureat reflux for three hours
  8. concentrationThe reaction was concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in chloroform (200 mL)
  10. washThe resulting solution was washed with brine (3×150 mL)
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered through a layer of CELITE
  13. filtrationfilter aid
  14. concentrationconcentrated under reduced pressure
  15. dissolutionThe mixture was dissolved in tetrahydroiiran (200 mL)
  16. stirringThe reaction was stirred overnight at room temperature
  17. customwhich was isolated by filtration
  18. washwashed with tetrahydrofuran

Sources & evidence

ORD record
ord-b6f7d065bd49439b920596e5ba3756a0
Source dataset
uspto-grants-2014_03
Patent number
US08673932B2

Reaction notes

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