Chloromethyl methyl sulfide → 3-[[5-Chloro-2-(methylthiomethoxy)phenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one

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Reaction Steps

A solution of 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one (6.0 g, 16.2 mmol) in dry HMPA (50 mL) was added dropwise under nitrogen to a stirred suspension of sodium hydride (0.77 g of 60% dispersion in mineral oil, 19.4 mmol) in HMPA (15 mL). The resultant yellow solution was stirred for 30 min and then neat chloromethyl methyl sulfide (1.49 mL, 17.8 mmol) was added dropwise. The reaction mixture was stirred at room temperature overnight and the product was extracted with ethyl acetate (500 mL). The EtOAc layer was washed with satd. NaHCO3, water, brine and then dried (MgSO4). Rotary evaporation of EtOAc gave a yellow semi-solid which was recrystallized from ethyl acetate/hexanes to afford the title compound as white crystals (4.4 g, 70%).

Provenance & Evidence