(alphaR,betaR)-beta-(2,5-Difluorophenyl)-beta-hydroxy-alpha-methyl-1H-1,2,4-triazole-1-butanethioamide → 2-(2,5-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol

HRID 379669Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@:9]([OH:21])([CH2:15][N:16]1[CH:20]=[N:19][CH:18]=[N:17]1)[C@@H:10](C)[C:11](N)=S>CCO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]([OH:21])([CH2:10][CH3:11])[CH2:15][N:16]1[CH:20]=[N:19][CH:18]=[N:17]1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (2R,3R)-3-(2,5-difluoro-phenyl)-3-hydroxy-2-methyl-4-[1,2,4]triazol-1-ylthiobutyramide (106 g, 340 mmol) in EtOH (500 mL) warmed at 50° C. in a water-bath was added 4-cyano-2′-bromoacetophenone (78.4 g, 350 mmol) portionwise over a period of 15 min and the mixture was stirred for 2 h at 50° C. After evaporation of EtOH under reduced pressure, the residue was dissolved in EtOAc (1.2 L) and the solution was washed with sat. NaHCO3 and brine, dried over MgSO4 and evaporated under reduced pressure. The residue was purified by column chromatography followed by trituration with t-BuOMe to give pure (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl)]-2-(2,5-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol (117 g, 79%) as a white powdery crystal.

Workup

customAfter evaporation of EtOH under reduced pressure
dissolutionthe residue was dissolved in EtOAc (1.2 L)
washthe solution was washed with sat. NaHCO3 and brine
dry with materialdried over MgSO4
customevaporated under reduced pressure
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-76dc76bc1ee94ed7810bd661bf62862c
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06300353B1

Reaction notes

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