Cyclohexanol → N-cyclohexyloxyphthalimide

HRID 1166504Notes

Reaction equation

HRID 1166504 reaction equation
[CH:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O[N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19].N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[CH:1]1([O:7][N:9]2[C:13](=[O:14])[C:12]3[C:11](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:10]2=[O:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 7966CyclohexanolHCID 10665N-HydroxyphthalimideHCID 97268Di-tert-butyl azodicarboxylate2×

Product 1

HCID 10467039N-cyclohexyloxyphthalimideYield 75.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of triphenylphosine (15.53 g, 59.2 mmol), cyclohexanol (6.25 mL, 59.2mmol), and N-hydroxypthalimide (9.66 g, 59.2 mmol) in anhydrous tetrahydrofuran (500 mL) under Argon was treated dropwise over approximately 20 minutes with a solution of di-tert-butyl azodicarboxylate (15.00 g, 65.14 mmol) in tetrahydrofuran (100 mL) with a water bath to control the exotherm. After the reddish color had dissipated, a mixture of di-tert-butyl azodicarboxylate (3.00 g, 13.0 mmol) and triphenylphosine (3.11 g, 11.8 mmol) in anhydrous tetrahydrofuran (50 mL) was added to the reaction mixture and allowed to stir overnight at ambient temperature. After evaporation in vacuo, the residue was treated with trifluoroacetic acid (100 mL) and stirred for 20 minutes. The reaction was evaporated in vacuo and the residue was partitioned between water and dichloromethane. The layers were separated and the aqueous phase was extracted with dichloromethane. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue. The crude material was purified twice by flash silica gel chromatography eluting with hexane : ethyl acetate (4:1 and 9:1). Pure fractions were concentrated in vacuo to a solid and dried under high vacuum to provide 2-(cyclohexyloxy)-1H-isoindole-1,3(2H)-dione as a solid (10.90 g, 75%).

Workup

  1. additionwas added to the reaction mixture
  2. customAfter evaporation in vacuo
  3. additionthe residue was treated with trifluoroacetic acid (100 mL)
  4. stirringstirred for 20 minutes
  5. customThe reaction was evaporated in vacuo
  6. customthe residue was partitioned between water and dichloromethane
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with dichloromethane
  9. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customevaporated in vacuo to a residue
  12. customThe crude material was purified twice by flash silica gel chromatography
  13. washeluting with hexane : ethyl acetate (4:1 and 9:1)
  14. concentrationPure fractions were concentrated in vacuo to a solid
  15. customdried under high vacuum

Sources & evidence

ORD record
ord-37e96752fb424fdd9aefb925c8a2ce33
Source dataset
uspto-grants-2003_09
Patent number
US06613743B2

Reaction notes

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