Hydrogen Peroxide → Dibenzyl (2RS,3RS)-3-(4-[4-cyanophenyl]thiazol-2-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butyl phosphate

Participants

Reaction Conditions

Reaction Steps

3-[4-(4-Cyanophenyl)thiazol-2-yl]-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (Example 88, EP 0667346, 900 mg, 2.06 mmol), 1H-tetrazole (432 mg, 6.18 mmol), 4-dimethylaminopyridine (100 mg, 0.82 mmol) and dibenzyl diisopropylphosphoramidite (1.42 g, 4.12 mmol) in methylene chloride (10 ml) were refluxed under a nitrogen atmosphere for 20 hours. The mixture was then cooled to 0° C., and hydrogen peroxide (2.5 ml, 30% solution in water) was added dropwise maintaining the temperature below 20° C. The resulting mixture was stirred at 20° C. for 30 minutes before separating the organic layer, which was washed with water, dried (MgSO4) and the solvent evaporated. The resulting pale yellow oil was purified by column chromatography (silica gel, eluting with ethyl acetate/hexane) to give the subtitle compound as a viscous syrup (732 mg, 51%).

Provenance & Evidence