Cesium carbonate → 4-isopropyl-6-hydroxy-2-[1-(4-chlorophenyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

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Reaction Steps

A mixture of 1-(4-chlorophenyl)-3-trifluoromethyl-5-hydroxypyrazole (8.4 g; 32 mmol) and Cs2CO3 (5.22 g; 16 mmol) in methanol (140 ml) was stirred at room temperature for 1.5 hours. The solvent was concentrated in vacuo, and the residue was dried in vacuo overnight. To the above residue was added 133 ml of DMF, cooled to 0° C., and 2-bromomethyl-4-isopropyl-6-hydroxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (5.33 g, 16 mmol) and the resulting mixture was stirred at room temperature for 24 hours and poured into ice/water. The resulting solid was filtered, the solid was dissolved in ether (700 ml), the organic layer was washed with brine (2×200 ml), and concentrated in vacuo. The residue was purified by column chromatography (silica gel; 14-75% ethyl acetate/hexane) and recrystallized from methanol to afford 4.54 g (55%) of 4-isopropyl-6-hydroxy-2-[1-(4-chlorophenyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =4-Cl--Ph; R2 =CH3 ; R3 =H; R4 =CH(CH3)2 ; R5 =6-OH) as a white solid.

Provenance & Evidence