Cesium bicarbonate → 3-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

HRID 1746124Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1746124
COC(=O)[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][N:5]=1.Br[C:13]1[CH2:17][CH:16](C2C=CC(OC(F)(F)F)=CC=2)[O:15][N:14]=1.C(=O)([O-])O.[Cs+].O1C=CCN1>CN(C)C=O>[N:5]1[CH:4]=[CH:9][CH:8]=[C:7]([O:10][C:13]2[CH2:17][CH2:16][O:15][N:14]=2)[CH:6]=1

Komponenten

6

Edukt 4

HCID 2734983Cesium bicarbonateHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate2×HCID 193504172,3-Dihydro-1,2-oxazoleHCID 668180493-Bromo-5-(4-(trifluoromethoxy)phenyl)-4,5-dihydroisoxazole

Produkt 1

HCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-96a and I-96b were prepared in 1 step from racemic compound I-14 and 5-hydroxypicolinic acid methyl ester according to the following procedure: 3-bromo-5-(4-(trifluoromethoxy)phenyl)-4,5-dihydroisoxazole (1.0 equiv), 5-hydroxypicolinic acid methyl ester (1.2 equiv), and cesium hydrogencarbonate (1.50 equiv) are suspended in N,N-dimethylforamide (0.32 M with respect to dihydroisoxazole. The mixture is then degassed with argon after which it is heated to 130° C. for 4 h after which point there is only desired product and corresponding acid visible by LC/MS. The reaction is allowed to cool to room temperature and quenched by pouring into a solution of ammonium chloride in water (30% by weight, 0.08 M with respect to dihydroisoxazole). The aqueous phase is extracted with ethyl acetate (2×), dried over sodium sulfate, filtered and concentrated to product a brown solid which could be recystallized from absolute ethanol to provide racemic 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-96 that was isolated by filtration as a white solid (25% yield). These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=383.8 m/z. Activity: A

Aufarbeitung

  1. customThe mixture is then degassed with argon after which it
  2. temperatureto cool to room temperature
  3. customquenched
  4. additionby pouring into a solution of ammonium chloride in water (30% by weight, 0.08 M with respect to dihydroisoxazole)
  5. extractionThe aqueous phase is extracted with ethyl acetate (2×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to product a brown solid which

Quellen und Nachweise

ORD-Eintrag
ord-b5b665911c20495bbf0b390b1412e278
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09149465B2

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