Potassium Iodide → 1-[-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine

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Reaction Conditions

Reaction Steps

A mixture of 10 g of sodium bicarbonate, and 0.10 g of potassium iodide, 4.13 g of 4-(2,3,4,5,6-pentafluorophenoxy)piperidine and 75 ml of dimethylformamide was treated with a solution of 3.41 g of 3-(3-chloropropyl)-6-fluoro-1,2-benzisoxazole in 25 ml dimethylformamide and stirred at 68° C. for 5.5 hours. The mixture was then cooled, poured into water, and then extracted with ethyl acetate. The organic layer was washed with water followed by a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, evaporation of the volatiles afforded a residue which was purified by means of high pressure liquid chromatography (silica gel; elution with ethyl acetate) to yield 2.63 g of 1-[-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine as an oil. The oil was dissolved in diethyl ether and the solution acidified to pH 1 with etheral hydrogen chloride to precipitate the corresponding hydrochloride salt. Recrystallization from isopropanol afforded 1.80 g (15.4%) of 1-[ -(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine hydrochloride, m.p. 187°-189° C.

Provenance & Evidence