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

HRID 264793Notes

Reaction equation

HRID 264793 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.[H][H].[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[C@@:18]1([O:25][CH2:24]1)[C@@H:19]([CH3:23])[C:20]([OH:22])=[O:21].[NH4+].[Cl-]>CN(C=O)C>[F:10][C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:12]=1[C@@:18]([OH:25])([CH2:24][N:3]1[CH:7]=[N:6][CH:5]=[N:4]1)[C@@H:19]([CH3:23])[C:20]([OH:22])=[O:21]

Participants

7

Reactant 5

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 10242864(2R,3S)-3-(2,4-difluorophenyl)-3,4-epoxy-2-methylbutanoic acidHCID 178418361HCID 178418361, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To a cooled (0° C.) suspension of NaH (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,3S)-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 (3×). The collected organic fractions were then dried over anhydrous Na2SO4, the drying agent was filtered and the flitrate was concentrated under reduced pressure to a white solid. Recrystallization from EtOAc afforded the title product as a white solid.

Workup

  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 (3×)
  7. dry with materialThe collected organic fractions were then dried over anhydrous Na2SO4
  8. filtrationthe drying agent was filtered
  9. concentrationthe flitrate was concentrated under reduced pressure to a white solid
  10. customRecrystallization from EtOAc

Sources & evidence

ORD record
ord-9baeba50311d4d9597f3a37f92312281
Source dataset
uspto-grants-1997_07
Patent number
US05646294

Reaction notes

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