1H-1,2,4-Triazole → Simeconazole

Participants

Reaction Conditions

Reaction Steps

1.62 g (0.04 mole) of a 60% w/v dispersion of sodium hydride in mineral oil were added to 60 ml of dimethylformamide. Whilst the mixture was being stirred in an ice bath, 2.91 g (0.04 mole) of 1,2,4-triazole were added, and the mixture was stirred for a further 30 minutes at room temperature. At the end of this time, 5.5 g (0.021 mole) of 1 chloro-2-(4-fluorophenyl)-3-trimethylsilyl-2-propanol (prepared as described in Example 40) were added to the reaction mixture, which was then heated for 30 minutes at 90° C. whilst stirring. The reaction mixture was cooled and then poured into 200 ml of ice-water, and the resulting mixture was extracted with 300 ml of ethyl acetate. The organic extract was washed three times, each time with 100 ml of a saturated aqueous solution of sodium chloride. It was then dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure, to afford a crude oily product. 2.9 g (yield 47%) of the title compound, melting at 118 119° C., were obtained by purification of this crude oily product by silica gel column chromatography, using mixtures of ethyl acetate and hexane in proportions of 1:5, 1:1 and 2:1 as the eluent.

Provenance & Evidence