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

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Reaction Conditions

Reaction Steps

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.

Provenance & Evidence