Ammonium Chloride → (2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butyronitrile

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Reaction Conditions

Reaction Steps

Ytteribium chloride hexahydrate in an amount of 388 mg (1 mmol) was left over for 6 hours at 120° C. under reduced pressure. This compound was suspended in 10 ml of tetrahydrofuran in a nitrogen atmosphere, and the suspension was chilled to -78° C. To this suspension, 1.9 ml of n-butyllithium (1.63M hexane solution) were added dropwise, and the resultant mixture was stirred for 5 minutes at room temperature and then chilled to -78° C. To this mixture, 0.8 ml of trimethylsilyl cyanide was gently added dropwise. The resultant mixture was stirred for 10 minutes at -78° C. and then for 5 minutes at room temperature, and then chilled to -78° C. A solution with 128 mg (0.5 mmol) of optically active 2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-(1H-1,2,4-triazol-1-yl)methyloxirane dissolved in 1 ml of tetrahydrofuran was added dropwise to this mixture, and temperature of the resultant mixture was spontaneously raised to room temperature. A saturated aqueous solution of ammonium chloride was added to this mixture, followed by extraction with ethyl acetate. The resultant organic layer was washed with water and saturated saline. After the solvent was distilled out under reduced pressure, the residue was recrystallized from diethyl ether, thereby obtaining 81 mg (58.2%) of optically active (2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butyronitrile.

Provenance & Evidence