Реакция #57440

Уравнение реакции

di-tert-butyl azodicarboxylate

N-hydroxylphthalimide

triphenylphosphine

tetrahydro-4H-pyran-4-ol

→

2-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione

Растворители

THF

Условия реакции

Обработка

1. 1
   Другоеwere transferred to a flask
2. 2
   ДругоеThe solvent was removed under vacuum
3. 3
   workup.STIRRINGThe reaction was stirred for 30 minutes
4. 4
   Другоеthe TFA was removed under vacuum
5. 5
   workup.DISSOLUTIONThe crude residue was then dissolved in ethyl acetate
6. 6
   Промывкаwashed with a saturated aqueous solution of sodium bicarbonate, 5% aqueous solution of potassium carbonate, brine
7. 7
   Сушкаdried over magnesium sulfate
8. 8
   ДругоеThe solvent was removed under vacuum
9. 9
   Другоеthe residual triphenylphosphine oxide was crystallized
10. 10
    Фильтрацияfiltered
11. 11
    ДругоеThe solvent was again removed
12. 12
    Другоеthe crude solid was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and recrystallization

Методика

A light suspension containing N-hydroxylphthalimide (18.4 mmol, 3.0 g), triphenylphosphine (18.4 mmol, 4.82 g), tetrahydro-4H-pyran-4-ol (18.4 mmol, 1.75 mL) and anhydrous THF (50 mL), were transferred to a flask containing di-tert-butyl azodicarboxylate (20.2 mmol, 4.66 g) under nitrogen. Over 2 hours the reaction stirred at room temperature and changed from a dark orange to yellow in appearance. The solvent was removed under vacuum and replaced with trifluoroacetic acetic acid (10 mL). The reaction was stirred for 30 minutes and the TFA was removed under vacuum. The crude residue was then dissolved in ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate, 5% aqueous solution of potassium carbonate, brine and dried over magnesium sulfate. The solvent was removed under vacuum and the residual triphenylphosphine oxide was crystallized and filtered using hexanes and ether. The solvent was again removed and the crude solid was purified by silica gel chromatography (2:1 hexanes/ethyl acetate) and recrystallization using methylene chloride and hexanes providing 1.69 g (37%) of a white crystal. Rf=0.3 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.84-7.82 (2H,m), 7.75-7.73(2H,m), 4.46-4.40 (1H,m), 4.08-4.02 (2H,m), 3.50-3.44 (2H,m), 2.04-1.98 (2H,m), 1.92-1.84 (2H,m).

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