反应详情

A To a mixture of 2-chloro-4-(4-hydroxyphenyl)pyridine hydrobromide (593 m g) and potassium carbonate (1.66 g) in N,N-dimethylformamide (15 mL) heated at a temperature close to 65° C. is added (3S)-1-(3-methane-sulfonyloxypropyl)-3-methylpiperidine hydrochloride (625 mg). The mixture is heated at a temperature close to 65° C. for six hours, allowed to cool back to room temperature and filtered. The precipitate is washed with N,N-dimethylformamide and the organic phases are concentrated under reduced pressure. The residue is purified by column chromatography over silica gel (eluent dichloromethane/methanol from 100/0 to 90/10) to afford 434 mg of 2-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine as an orange oil. Conversion to the oxalate is performed by mixing the crude base (87 mg) and oxalic acid (46 mg) in a mixture of ethanol and diethyl ether. Filtration of the insoluble and drying under reduced pressure gives 82 mg of 2-chloro-4-(4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}phenyl)pyridine, dioxalate as an off white solid melting at 143° C.

1. temperatureheated at a temperature
2. customclose to 65° C.
3. temperatureThe mixture is heated at a temperature
4. customclose to 65° C. for six hours
5. filtrationfiltered
6. washThe precipitate is washed with N,N-dimethylformamide
7. concentrationthe organic phases are concentrated under reduced pressure
8. customThe residue is purified by column chromatography over silica gel (eluent dichloromethane/methanol from 100/0 to 90/10)