Реакция #158406

Уравнение реакции

diethyl azodicarboxylate

4-hydroxy-3,5-dimethylbenzonitrile

(R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol

triphenylphosphine

→

(R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylbenzonitrile

Выход 84.4%

Растворители

THF

Условия реакции

Обработка

1. 1
   ДругоеThe solution was made in a 500 ml flask
2. 2
   Другоеw/3 necks fitted with a reflux condenser for 10 min
3. 3
   ДругоеNitrogen was bubbled for an additional 10 minutes
4. 4
   ДругоеThe reaction vessel was immersed in a preheated oil bath
5. 5
   Другоеheld at 65° C
6. 6
   ТемператураThe contents of the reactor were cooled
7. 7
   Другоеevaporated
8. 8
   Промывкаwashed with water
9. 9
   ЭкстракцияThe aqueous layer was extracted with ether (2×)
10. 10
    ПромывкаThe combined organic layer was then washed with brine
11. 11
    СушкаIt was then dried over anhydrous MgSO4
12. 12
    Концентрирование, and then concentrated
13. 13
    ДругоеTriphenylphosphineoxide was crystallized out
14. 14
    Фильтрацияfiltered with ether and hexanes
15. 15
    ДругоеThe product was purified on a 330 g ISCo cartridge
16. 16
    Промывкаeluted with 0 to 30% EtOAc-hexanes

Методика

Nitrogen was bubbled in a solution of 4-hydroxy-3,5-dimethylbenzonitrile (5.0 g, 34.0 mmol) and (R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol (9.53 ml, 76 mmol) in THF (125 ml) at room temperature. The solution was made in a 500 ml flask w/3 necks fitted with a reflux condenser for 10 min. To this was added triphenylphosphine (20.05 g, 76 mmol) in one portion. Nitrogen was bubbled for an additional 10 minutes, followed by the dropwise addition of diethyl azodicarboxylate (12.04 ml, 76 mmol). The color of the reaction mixture changed from pale to a dark reddish brown and the reaction was exothermic. The reaction vessel was immersed in a preheated oil bath held at 65° C. The reaction was found to be nearly complete after 3 h. The contents of the reactor were cooled and evaporated. The semi solid residue was taken in ether and washed with water. The aqueous layer was extracted with ether (2×). The combined organic layer was then washed with brine. It was then dried over anhydrous MgSO4., and then concentrated. Triphenylphosphineoxide was crystallized out and filtered with ether and hexanes. The product was purified on a 330 g ISCo cartridge eluted with 0 to 30% EtOAc-hexanes. (R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylbenzonitrile (7.49 g, 28.7 mmol, 84% yield) was obtained as a clear oil. 1H NMR (400 MHz, CCl3D) δ ppm 7.27 (2H, s), 4.38-4.49 (1H, m), 4.08-4.19 (1H, m), 3.88 (1H, ddd, J=8.18, 5.99, 1.87 Hz), 3.73-3.84 (2H, m), 2.25 (6H, s), 1.41 (3H, s), 1.36 (3H, s).

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