Water → N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-3,4,5,6-tetrahydrophthalimide

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Reaction Steps

A solution of 4-chloro-5-cyclopentyloxy-2-fluoroaniline (0.50 g, 2.18 mmol) and 3,4,5,6-tetrahydrophthalic anhydride (0.398 g, 2.61 mmol) in acetic acids solution (3.0 mL) was stirred under reflux for 3 h. After completion of the reaction, water (20 mL) was added to the resulting reaction mixture and extraction was conducted with ethyl acetate (20 mL×3). The organic layers were dried with anhydrous magnesium sulfate and the solvent was distilled off under vacuum. The resulting pale yellow oil was separated and purified by silica gel column chromatography (ethyl acetate/hexane=1/8), giving N-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-3,4,5,6-tetrahydrophthalimide as a colorless clear oil (0.513 g, 1.41 mmol; yield=65%). This could be obtained as white solids upon addition of ethanol and subsequent recrystallization. MP: 69.0°-75.2° C. 1H-NMR(CDCl3,TMS,ppm): δ1.32-2.10(12H,m), 2.40(4H,m), 4.68(1H,m), 6.75(1H,d,JHF =7.0Hz), 7.20(1H, d,JHF =9.0Hz). IR (neat, cm-1): 1725, 1505, 1430, 1385, 1200.

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