Potassium tert-butoxide → 5-[5-Methyl-1-(4-{[tris(1-methylethyl)silyl]oxy}benzyl)-1H-pyrazol-3-yl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole

Participants

Reaction Steps

To a mechanically stirred solution of 5-(5-methyl-1H-pyrazol-3-yl)-3-[4-(trifluoromethoxy)-phenyl]-1,2,4-oxadiazole (Intermediate C, 600 mg, 1.93 mmol) and [4-(bromomethyl)-phenoxy][tris(1-methylethyl)]silane (Intermediate M, 1.11 g, 2.90 mmol) in dry THF (15 mL) was added potassium tert-butoxide (239 mg, 2.13 mmol) at a temperature of 0° C. The cooling bath was removed, and the reaction mixture was stirred at rt over night. After the addition of water (75 mL), the crude product was extracted into ethyl acetate (3×75 mL). The combined organic extracts were successively washed with water and brine, dried over anhydrous magnesium sulfate, followed by filtration and evaporation of the solvent. The residue was subjected to preparative HPLC to afford the title compound (519 mg, 47%) and, additionally, a considerable amount of the product of the next step (180 mg, 22%) which was formed by cleavage of the silicon-oxygen bond under the acidic HPLC conditions.

Provenance & Evidence