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

HRID 71224

Reaktionsgleichung

Reaktionsgleichung von HRID 71224
[OH:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH3:11].[CH3:12][C:13]1([CH3:20])[O:17][C@H:16]([CH2:18]O)[CH2:15][O:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:12][C:13]1([CH3:20])[O:17][C@H:16]([CH2:18][O:1][C:2]2[C:3]([CH3:11])=[CH:4][C:5]([C:6]#[N:7])=[CH:8][C:9]=2[CH3:10])[CH2:15][O:14]1

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 201763,5-Dimethyl-4-hydroxybenzonitrileHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 736056(R)-Solketal

Produkt 1

HCID 66692560(R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3,5-dimethylbenzonitrileAusbeute 84,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  1. customThe solution was made in a 500 ml flask
  2. customw/3 necks fitted with a reflux condenser for 10 min
  3. customNitrogen was bubbled for an additional 10 minutes
  4. customThe reaction vessel was immersed in a preheated oil bath
  5. customheld at 65° C
  6. temperatureThe contents of the reactor were cooled
  7. customevaporated
  8. washwashed with water
  9. extractionThe aqueous layer was extracted with ether (2×)
  10. washThe combined organic layer was then washed with brine
  11. dry with materialIt was then dried over anhydrous MgSO4
  12. concentration, and then concentrated
  13. customTriphenylphosphineoxide was crystallized out
  14. filtrationfiltered with ether and hexanes
  15. customThe product was purified on a 330 g ISCo cartridge
  16. washeluted with 0 to 30% EtOAc-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-6246ab172b834a90abc2d5d7aa9540cf
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822510B2

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