反应详情

A mixture of 4-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylbutanoic acid (4.0 g, 11.3 mmole), desmethyltropane (1.7 g, 15.3 mmole, prepared from tropane by the method used by R. A. Olofson et. al., J. Org. Chem., 1984, 49(11), 2081, for the conversion of O-acetyltropine to O-acetyldesmethyltropine), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.2 g, 11.3 mmole) and triethylamine (0.19.8 mmole) in methylene chloride (25 mL) was stirred at ambient temperature for 48 hr. The mixture was poured into 1 N sodium hydroxide (100 mL) and extracted with ethyl acetate (3×100 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 1% ammonia in ethyl acetate as eluant) followed by the treatment with 1.1 equivalent of 1N hydrogen chloride in ether gave 2.5 g of the title compound as the hydrochloride hemihydrate, m.p. 225°-228° C. (dec.).

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