Tetrabutylammonium Fluoride → 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile

HRID 2388505Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2388505
[Si]([O:8][C@@H:9]([CH3:34])[C@@H:10]([NH:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33])[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([I:22])=[CH:18][CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:32][C:26]1[C:25]([CH3:33])=[C:24]([NH:23][C@@H:10]([C:11]2[O:12][C:13]([C:16]3[CH:17]=[CH:18][C:19]([I:22])=[CH:20][CH:21]=3)=[N:14][N:15]=2)[C@@H:9]([OH:8])[CH3:34])[CH:31]=[CH:30][C:27]=1[C:28]#[N:29]

Komponenten

4

Edukt 2

HCID 2724141Tetrabutylammonium FluorideHCID 670064554-((1R,2S)-2-(tert-Butyldimethylsilyloxy)-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile

Produkt 1

HCID 670061822-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrileAusbeute 94,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-30 °C

Versuchsvorschrift

To a solution of 4-((1R,2S)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-2-chloro-3-methylbenzonitrile (2.0 g, 3.3 mmol) in THF (60 mL) was added TBAF (3.7 mL, 3.7 mmol, 1 M solution in THF) at −50° C. After addition, the reaction mixture was allowed to warm to −30° C. gradually (about 1 h), then quenched by adding saturated aqueous NH4Cl solution (20 mL) and extracted with EtOAc. The EtOAc extracts were washed with water, brine, dried over Na2SO4. Concentration provided a residue, which was purified by flash chromatography over silica gel to provide the title compound 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile (1.54 g, 94%). 1H NMR (400 MHz, CDCl3, δ in ppm) 7.83 (d, J=8.6 Hz, 2H), 7.64 (d, J=8.6 Hz, 2H), 7.40 (d, J=8.6 Hz, 1H), 6.63 (d, J=8.6 Hz, 1H), 5.24 (d, J=8.6 Hz, 1H), 4.72 (dd, J=2.6, 8.6 Hz, 1H), 4.62 (m, 1H), 3.07 (d, J=4.1 Hz, 1H), 2.35 (s, 3H), 1.42 (d, J=6.5 Hz, 3H).

Aufarbeitung

  1. additionAfter addition
  2. customquenched
  3. additionby adding saturated aqueous NH4Cl solution (20 mL)
  4. extractionextracted with EtOAc
  5. washThe EtOAc extracts were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. concentrationConcentration
  8. customprovided a residue, which
  9. customwas purified by flash chromatography over silica gel

Quellen und Nachweise

ORD-Eintrag
ord-4e0673dc46b14c12a542ae8696892cfd
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08268872B2

Notizen zur Reaktion

Wird geladen…