Reaction #57478

Reaction equation

di-tert-butyl azodicarboxylate

cyclohexanol

N-hydroxypthalimide

di-tert-butyl azodicarboxylate

→

2-(cyclohexyloxy)-1H-isoindole-1,3(2H)-dione

Yield 75.1%

Solvents

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.ADDITIONwas added to the reaction mixture
2. 2
   OtherAfter evaporation in vacuo
3. 3
   workup.ADDITIONthe residue was treated with trifluoroacetic acid (100 mL)
4. 4
   workup.STIRRINGstirred for 20 minutes
5. 5
   OtherThe reaction was evaporated in vacuo
6. 6
   Otherthe residue was partitioned between water and dichloromethane
7. 7
   OtherThe layers were separated
8. 8
   Extractionthe aqueous phase was extracted with dichloromethane
9. 9
   DryingThe combined organic layers were dried over anhydrous magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Otherevaporated in vacuo to a residue
12. 12
    OtherThe crude material was purified twice by flash silica gel chromatography
13. 13
    Washeluting with hexane:ethyl acetate (4:1 and 9:1)
14. 14
    ConcentrationPure fractions were concentrated in vacuo to a solid
15. 15
    Otherdried under high vacuum

Procedure

A solution of triphenylphosine (15.53 g, 59.2 mmol), cyclohexanol (6.25 mL, 59.2 mmol), 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%).

Source