反应详情

A mixture of the 4-(5-fluoro-2-methoxyphenyl)-piperazine (2.1 g, 10.0 mmole, prepared by method disclosed in U.S. Pat. No. 4,585,773), 1-(8-aza-bicyclo[3.2.1]oct-8-yl)-4-chloro-2-phenyl-butan-1-one (3.40 g, 10.0 mmole), diisopropylethylamine (1.4 g, 11.0 mmole) and potassium iodide (1.66 g, 10.0 mmole) was heated in dimethylformamide (35 mL) to 80° C. for 5 hours. After cooling to ambient temperature, the mixture was poured into water (100 mL) and extracted with ethyl acetate (2×300 mL). The combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum to give crude product. Purification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 1.3 g of the title compound as the hydrochloride quarter hydrate, m.p. 203°-206° C.

1. customprepared by method
2. extractionextracted with ethyl acetate (2×300 mL)
3. washThe combined ethyl acetate layer was washed with water (100 mL) and brine (100 mL)
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customto give crude product
8. customPurification of this material by column chromatoghaphy (silica gel with 2% methanol in ethyl acetate as eluant)