Реакция #57478

Уравнение реакции

di-tert-butyl azodicarboxylate

cyclohexanol

N-hydroxypthalimide

di-tert-butyl azodicarboxylate

→

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

Выход 75.1%

Растворители

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Условия реакции

Обработка

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

Методика

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%).

Источник