1H-1,2,4-Triazole → (Alphar,betar)-beta-(2,4-difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanoic acid

HRID 2260512Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2260512
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H][H].[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@:16]1([O:23][CH2:22]1)[C@@H:17]([CH3:21])[C:18]([OH:20])=[O:19].[NH4+].[Cl-]>CN(C=O)C.CCCCCC>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C@@:16]([OH:23])([CH2:22][N:1]1[CH:5]=[N:4][CH:3]=[N:2]1)[C@@H:17]([CH3:21])[C:18]([OH:20])=[O:19]

Komponenten

7

Edukt 4

HCID 92571H-1,2,4-TriazoleHCID 25517Ammonium ChlorideHCID 10353712(2R,3R)-3-(2,4-Difluorophenyl)-3,4-epoxy-2-methylbutanoic acidHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 10040259(Alphar,betar)-beta-(2,4-difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a cooled (0° C.) suspension of Nail (55% mineral oil dispersion, 288 mg, 6.6 mmol, washed with hexane) in DMF (25 mL) was added 1,2,4-triazole (0.5 g, 7.2 mmol) and the mixture was stirred at 0° C. until hydrogen gas ceased to evolve. Then, a solution of unpurified (2R,3R)-3-(2,4-difluorophenyl)-3,4-epoxy-2-methylbutanoic acid (0.5 g) (obtained in reference example 29) in DMF (3 mL) was slowly added and the mixture was heated to 60° C. during 2 h. A saturated NH4Cl aqueous solution was then added and the solvents were removed in vacuo. The mixture was then partitioned between brine containing AcOH and EtOAc. The organic layer was separated and the aqueous phase was extracted with more EtOAc (3x). The collected organic fractions were then dried over anhydrous Na2SO4, the drying agent was filtered and the filtrate was concentrated under reduced pressure to a white solid. Recrystallization from EtOAc afforded the title product as a white solid.

Aufarbeitung

  1. temperatureTo a cooled
  2. customthe solvents were removed in vacuo
  3. customThe mixture was then partitioned between brine
  4. additioncontaining AcOH and EtOAc
  5. customThe organic layer was separated
  6. extractionthe aqueous phase was extracted with more EtOAc (3x)
  7. dry with materialThe collected organic fractions were then dried over anhydrous Na2SO4
  8. filtrationthe drying agent was filtered
  9. concentrationthe filtrate was concentrated under reduced pressure to a white solid
  10. customRecrystallization from EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-1930ae02423e47d78cb099e8936865c0
Quelldatensatz
uspto-grants-1995_12
Patentnummer
US05478826

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