4-(chloromethyl)-1-oxidopyridin-1-ium

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2 N aqueous sodium hydroxide solution (10 mL) and water (20 mL) were added to 4-(chloromethyl)pyridine hydrochloride (1.6 g, 10 mmol), and the reaction mixture was extracted with chloroform (20 mL) twice. The chloroform layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. m-Chloroperoxybenzoic acid (65%, 5.3 g, 20 mmol) was added to a solution of the resulting residue in dichloromethane (20 mL), and then the mixture was stirred at room temperature for 17 hours. Chloroform (100 mL) and a saturated aqueous sodium hydrogencarbonate solution (120 mL) were added to the reaction mixture, and then the chloroform layer was washed with a saturated aqueous sodium hydrogencarbonate solution (80 ml) and brine (100 mL). The chloroform layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 300 mg of the title reference compound as a brown solid. (Yield 21%) the reaction mixture was extracted with chloroform (20 mL) twice The chloroform layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure the chloroform layer was washed with a saturated aqueous sodium hydrogencarbonate solution (80 ml) and brine (100 mL) The chloroform layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The resulting residue was purified by silica gel column chromatography to give 300 mg of the title reference compound as a brown solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a DMF (10 ml) solution of 1.50 g of 4-{4-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]piperazin-1-yl}phenol were added 1.00 g of 4-chloromethylpyridine-N-oxide and 3.00 g of cesium carbonate, followed by 30 minutes of stirring at room temperature. After warmed to 60° C., the mixture was further stirred for 30 minutes. Then, 1.00 g of 4-chloromethylpyridine-N-oxide and 1.50 g of cesium carbonate were added thereto and the whole was stirred at 60° C. for 1 hour. After cooling to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous magnesium sulfate, and thereafter, the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform-methanol) and then recrystallization was carried out from ethanol to obtain 440 mg of 1-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]-4-[4-(1-oxido-4-pyridylmethoxy)phenyl]piperazine as pale yellow crystals. After warmed to 60° C. the mixture was further stirred for 30 minutes the whole was stirred at 60° C. for 1 hour After cooling to room temperature followed by extraction with ethyl acetate The organic layer was washed with water and brine dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified by silica gel column chromatography (chloroform-methanol) recrystallization

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2 N aqueous sodium hydroxide solution (10 mL) and water (20 mL) were added to 4-(chloromethyl)pyridine hydrochloride (1.6 g, 10 mmol), and the reaction mixture was extracted with chloroform (20 mL) twice. The chloroform layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. m-Chloroperoxybenzoic acid (65%, 5.3 g, 20 mmol) was added to a solution of the resulting residue in dichloromethane (20 mL), and then the mixture was stirred at room temperature for 17 hours. Chloroform (100 mL) and a saturated aqueous sodium hydrogencarbonate solution (120 mL) were added to the reaction mixture, and then the chloroform layer was washed with a saturated aqueous sodium hydrogencarbonate solution (80 ml) and brine (100 mL). The chloroform layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 300 mg of the title reference compound as a brown solid. (Yield 21%) the reaction mixture was extracted with chloroform (20 mL) twice The chloroform layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure the chloroform layer was washed with a saturated aqueous sodium hydrogencarbonate solution (80 ml) and brine (100 mL) The chloroform layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The resulting residue was purified by silica gel column chromatography to give 300 mg of the title reference compound as a brown solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2 N aqueous sodium hydroxide solution (10 mL) and water (20 mL) were added to 4-(chloromethyl)pyridine hydrochloride (1.6 g, 10 mmol), and the reaction mixture was extracted with chloroform (20 mL) twice. The chloroform layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. m-Chloroperoxybenzoic acid (65%, 5.3 g, 20 mmol) was added to a solution of the resulting residue in dichloromethane (20 mL), and then the mixture was stirred at room temperature for 17 hours. Chloroform (100 mL) and a saturated aqueous sodium hydrogencarbonate solution (120 mL) were added to the reaction mixture, and then the chloroform layer was washed with a saturated aqueous sodium hydrogencarbonate solution (80 ml) and brine (100 mL). The chloroform layer was dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give 300 mg of the title reference compound as a brown solid. (Yield 21%) the reaction mixture was extracted with chloroform (20 mL) twice The chloroform layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure the chloroform layer was washed with a saturated aqueous sodium hydrogencarbonate solution (80 ml) and brine (100 mL) The chloroform layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The resulting residue was purified by silica gel column chromatography to give 300 mg of the title reference compound as a brown solid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a DMF (10 ml) solution of 1.50 g of 4-{4-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]piperazin-1-yl}phenol were added 1.00 g of 4-chloromethylpyridine-N-oxide and 3.00 g of cesium carbonate, followed by 30 minutes of stirring at room temperature. After warmed to 60° C., the mixture was further stirred for 30 minutes. Then, 1.00 g of 4-chloromethylpyridine-N-oxide and 1.50 g of cesium carbonate were added thereto and the whole was stirred at 60° C. for 1 hour. After cooling to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and brine and then dried over anhydrous magnesium sulfate, and thereafter, the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform-methanol) and then recrystallization was carried out from ethanol to obtain 440 mg of 1-[6-(3,4-dimethoxyphenyl)pyridine-2-carbonyl]-4-[4-(1-oxido-4-pyridylmethoxy)phenyl]piperazine as pale yellow crystals. After warmed to 60° C. the mixture was further stirred for 30 minutes the whole was stirred at 60° C. for 1 hour After cooling to room temperature followed by extraction with ethyl acetate The organic layer was washed with water and brine dried over anhydrous magnesium sulfate the solvent was evaporated The residue was purified by silica gel column chromatography (chloroform-methanol) recrystallization