methyl 4-piperidin-4-ylbutanoate;hydrochloride

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 18 ml (0.242 mol) of thionyl chloride are slowly added dropwise to 800 ml of methanol at -10° C., while stirring. A solution of 44.3 g (0.201 mol) of 4-(4-piperidinyl)-butyric acid hydrochloride in 100 ml of methanol is then added dropwise at the same temperature, stirring is continued overnight at room temperature and the mixture is then concentrated to dryness in vacuo. The residue is partitioned between 50% strength potassium carbonate solution and ether. The aqueous phase is extracted twice more with ether. The combined ether extracts are dried and concentrated. The residue is dissolved in methanol and the solution is acidified to pH 6 with ethereal hydrochloric acid and concentrated to dryness in vacuo. The residue which remains is triturated with acetone. The crystals which have separated out are filtered off with suction. stirring the mixture is then concentrated to dryness in vacuo The residue is partitioned between 50% strength potassium carbonate solution and ether The aqueous phase is extracted twice more with ether The combined ether extracts are dried concentrated The residue is dissolved in methanol concentrated to dryness in vacuo The residue which remains is triturated with acetone The crystals which have separated out are filtered off with suction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol) and cesium carbonate (1.30 g; 4.00 mmol) in dioxane (3 mL) is placed in an ultrasonic bath for 45 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (415 mg; 2.0 mmol, prepared in accordance with Example 131) and 1-bromo-4-tert-butyl-benzene (426 mg; 2.00 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. New catalyst solution (prepared as above from palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol), cesium carbonate (1.30 g; 4.00 mmol) and dioxane (3 mL) is prepared with the aid of an ultrasonic bath and added to the reaction mixture. After stirring under reflux for 3 hours, the mixture is diluted with ethyl acetate and is filtered. The filtrate is concentrated under high vacuum and the obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (385 mg; 1.21 mmol). under reflux is prepared with the aid of an ultrasonic bath added to the reaction mixture After stirring under reflux for 3 hours is filtered The filtrate is concentrated under high vacuum the obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of palladium (II) acetate (42 mg; 0.185 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (170 mg; 0.275 mmol), cesium carbonate (867 g; 2.66 mmol) in dioxane (5 mL) is placed in an ultrasonic bath for 30 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (290 mg; 1.33 mmol, prepared in accordance with Example 131) and 1-bromo-4-trifluoromethyl-benzene (299 mg; 1.33 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. After dilution with ethyl acetate, the mixture is filtered and the filtrate concentrated under high vacuum. The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (284 mg; 0.86 mmol). under reflux After dilution with ethyl acetate, the mixture is filtered the filtrate concentrated under high vacuum The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-piperidin-4-yl-butyric acid (1.1 g; 5.30 mmol) in methanol (5 mL) is added thionylchloride (0.69 g; 5.80 mmol) and the reaction mixture is stirred at room temperature for 2 hours. All volatiles are then removed under high vacuum and the resulting residue triturated with diethyl ether, sucked to dryness and washed (diethyl ether) to afford the desired compound (1.06 g; 4.8 mmol). All volatiles are then removed under high vacuum the resulting residue triturated with diethyl ether washed (diethyl ether)

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 18 ml (0.242 Mol) of thionyl chloride are slowly added dropwise to 800 ml of methanol with stirring at -10° C. then, at the same temperature, a solution of 44.3 g(0.201 Mol) of 4-(4-piperidinyl)-butyric acid hydrochloride in 100 ml of methanol is added dropwise, the resulting mixture is stirred overnight at ambient temperature and then evaporated to dryness in vacuo. The residue is partitioned between 50% potassium carbonate solution and ether. The aqueous phase is extracted twice more with ether. The combined ether extracts are dried and evaporated down. The residue is dissolved in methanol, acidified to pH 6 with ethereal hydrochloric acid and evaporated to dryness in vacuo. The residue remaining is triturated with acetone. The crystals precipitated are suction filtered. the resulting mixture is stirred overnight at ambient temperature evaporated to dryness in vacuo The residue is partitioned between 50% potassium carbonate solution and ether The aqueous phase is extracted twice more with ether The combined ether extracts are dried evaporated down The residue is dissolved in methanol evaporated to dryness in vacuo The residue remaining is triturated with acetone The crystals precipitated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 18 ml (0.242 mol) of thionyl chloride are slowly added dropwise to 800 ml of methanol at -10° C., while stirring. A solution of 44.3 g (0.201 mol) of 4-(4-piperidinyl)-butyric acid hydrochloride in 100 ml of methanol is then added dropwise at the same temperature, stirring is continued overnight at room temperature and the mixture is then concentrated to dryness in vacuo. The residue is partitioned between 50% strength potassium carbonate solution and ether. The aqueous phase is extracted twice more with ether. The combined ether extracts are dried and concentrated. The residue is dissolved in methanol and the solution is acidified to pH 6 with ethereal hydrochloric acid and concentrated to dryness in vacuo. The residue which remains is triturated with acetone. The crystals which have separated out are filtered off with suction. stirring the mixture is then concentrated to dryness in vacuo The residue is partitioned between 50% strength potassium carbonate solution and ether The aqueous phase is extracted twice more with ether The combined ether extracts are dried concentrated The residue is dissolved in methanol concentrated to dryness in vacuo The residue which remains is triturated with acetone The crystals which have separated out are filtered off with suction

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol) and cesium carbonate (1.30 g; 4.00 mmol) in dioxane (3 mL) is placed in an ultrasonic bath for 45 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (415 mg; 2.0 mmol, prepared in accordance with Example 131) and 1-bromo-4-tert-butyl-benzene (426 mg; 2.00 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. New catalyst solution (prepared as above from palladium (II) acetate (63 mg; 0.28 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (258 mg; 0.41 mmol), cesium carbonate (1.30 g; 4.00 mmol) and dioxane (3 mL) is prepared with the aid of an ultrasonic bath and added to the reaction mixture. After stirring under reflux for 3 hours, the mixture is diluted with ethyl acetate and is filtered. The filtrate is concentrated under high vacuum and the obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (385 mg; 1.21 mmol). under reflux is prepared with the aid of an ultrasonic bath added to the reaction mixture After stirring under reflux for 3 hours is filtered The filtrate is concentrated under high vacuum the obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of palladium (II) acetate (42 mg; 0.185 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (170 mg; 0.275 mmol), cesium carbonate (867 g; 2.66 mmol) in dioxane (5 mL) is placed in an ultrasonic bath for 30 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (290 mg; 1.33 mmol, prepared in accordance with Example 131) and 1-bromo-4-trifluoromethyl-benzene (299 mg; 1.33 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. After dilution with ethyl acetate, the mixture is filtered and the filtrate concentrated under high vacuum. The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (284 mg; 0.86 mmol). under reflux After dilution with ethyl acetate, the mixture is filtered the filtrate concentrated under high vacuum The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-piperidin-4-yl-butyric acid (1.1 g; 5.30 mmol) in methanol (5 mL) is added thionylchloride (0.69 g; 5.80 mmol) and the reaction mixture is stirred at room temperature for 2 hours. All volatiles are then removed under high vacuum and the resulting residue triturated with diethyl ether, sucked to dryness and washed (diethyl ether) to afford the desired compound (1.06 g; 4.8 mmol). All volatiles are then removed under high vacuum the resulting residue triturated with diethyl ether washed (diethyl ether)