1-phenyl-3-piperidin-1-ylpropan-1-amine

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

Procedure: To a suspension of 866 mg (5.0 mmol.) of quinaldinic acid and 576 mg (5.0 mmol.) of 1-hydroxysuccinimide in 20 ml of ethyl acetate was dropwise added over a period of 5-10 min. under chilling with ice a solution of 1.09 g (5.0 mmol.) of N,N'-dicyclohexylcarbodiimide. After the addition was complete, the mixture was stirred for 2 hours at room temperature. To this mixture was dropwise added a solution of 1.09 g (5.0 mmol.) of 1-(3-amino-3-phenylpropyl)piperidine in 5 ml of ethyl acetate. After the addition was complete, the mixture was stirred overnight at room temperature. Precipitated insolubles were filtered off and then the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution. The mixture was then dried over sodium sulfate, and was evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (silica gel: 20 g, CHCl3 and CHCl3 /CH3OH (30:1)) to obtain 1.72 g (yield: 92%) of the subject compound as a pale yellow crystalline product. was dropwise added over a period of 5-10 min. After the addition After the addition the mixture was stirred overnight at room temperature Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution The mixture was then dried over sodium sulfate was evaporated under reduced pressure to remove the solvent The residue was purified by silica gel column chromatography (silica gel: 20 g, CHCl3 and CHCl3 /CH3OH (30:1))

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

Procedure: To a solution of 1.73 g (10 mmol.) of quinaldinic acid and 1.53 g (10 mmol.) of 1-hydroxybenzotriazole monohydrate in 50 ml of ethyl acetate was dropwise added over a period of 20 min. under chilling with ice a solution of 2.06 g (10 mmol.) of N,N'-dicyclohexylcarbodiimide in 10 ml of ethyl acetate. After the addition was complete, the resulting mixture was stirred for 2 hours at room temperature and chilled with ice. To the chilled mixture was dropwise added over a period of 30 min. a solution of 2.18 g (10 mmol.) of 1-(3-amino-3-phenylpropyl)piperidine in 8 ml of ethyl acetate. After the addition was complete, the mixture was stirred overnight at room temperature. Precipitated insolubles were filtered off and then the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution. The mixture was then dried over sodium sulfate, and was evaporated under reduced pressure to remove the solvent. The residue was crystallized after addition of n-hexane. The resulting crystals were washed three times with n-hexane and dissolved in 35 ml of ethyl acetate. The resulting solution was allowed to stand overnight in a refrigerator. Precipitated insolubles were filtered off and the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (silica gel: 40 g, CHCl3 and CHCl3 /CH3OH (30:1)) to obtain 3.07 g (yield: 82%) of the subject compound as a pale yellow crystalline product. After the addition chilled with ice After the addition the mixture was stirred overnight at room temperature Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution The mixture was then dried over sodium sulfate was evaporated under reduced pressure to remove the solvent The residue was crystallized after addition of n-hexane The resulting crystals were washed three times with n-hexane dissolved in 35 ml of ethyl acetate to stand overnight in a refrigerator Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate concentrated under reduced pressure The residue was purified by silica gel column chromatography (silica gel: 40 g, CHCl3 and CHCl3 /CH3OH (30:1))

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: To a suspension of 866 mg (5.0 mmol.) of quinaldinic acid and 576 mg (5.0 mmol.) of 1-hydroxysuccinimide in 20 ml of ethyl acetate was dropwise added over a period of 5-10 min. under chilling with ice a solution of 1.09 g (5.0 mmol.) of N,N'-dicyclohexylcarbodiimide. After the addition was complete, the mixture was stirred for 2 hours at room temperature. To this mixture was dropwise added a solution of 1.09 g (5.0 mmol.) of 1-(3-amino-3-phenylpropyl)piperidine in 5 ml of ethyl acetate. After the addition was complete, the mixture was stirred overnight at room temperature. Precipitated insolubles were filtered off and then the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution. The mixture was then dried over sodium sulfate, and was evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (silica gel: 20 g, CHCl3 and CHCl3 /CH3OH (30:1)) to obtain 1.72 g (yield: 92%) of the subject compound as a pale yellow crystalline product. was dropwise added over a period of 5-10 min. After the addition After the addition the mixture was stirred overnight at room temperature Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution The mixture was then dried over sodium sulfate was evaporated under reduced pressure to remove the solvent The residue was purified by silica gel column chromatography (silica gel: 20 g, CHCl3 and CHCl3 /CH3OH (30:1))

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

Procedure: To a solution of 1.73 g (10 mmol.) of quinaldinic acid and 1.53 g (10 mmol.) of 1-hydroxybenzotriazole monohydrate in 50 ml of ethyl acetate was dropwise added over a period of 20 min. under chilling with ice a solution of 2.06 g (10 mmol.) of N,N'-dicyclohexylcarbodiimide in 10 ml of ethyl acetate. After the addition was complete, the resulting mixture was stirred for 2 hours at room temperature and chilled with ice. To the chilled mixture was dropwise added over a period of 30 min. a solution of 2.18 g (10 mmol.) of 1-(3-amino-3-phenylpropyl)piperidine in 8 ml of ethyl acetate. After the addition was complete, the mixture was stirred overnight at room temperature. Precipitated insolubles were filtered off and then the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution. The mixture was then dried over sodium sulfate, and was evaporated under reduced pressure to remove the solvent. The residue was crystallized after addition of n-hexane. The resulting crystals were washed three times with n-hexane and dissolved in 35 ml of ethyl acetate. The resulting solution was allowed to stand overnight in a refrigerator. Precipitated insolubles were filtered off and the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (silica gel: 40 g, CHCl3 and CHCl3 /CH3OH (30:1)) to obtain 3.07 g (yield: 82%) of the subject compound as a pale yellow crystalline product. After the addition chilled with ice After the addition the mixture was stirred overnight at room temperature Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution The mixture was then dried over sodium sulfate was evaporated under reduced pressure to remove the solvent The residue was crystallized after addition of n-hexane The resulting crystals were washed three times with n-hexane dissolved in 35 ml of ethyl acetate to stand overnight in a refrigerator Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate concentrated under reduced pressure The residue was purified by silica gel column chromatography (silica gel: 40 g, CHCl3 and CHCl3 /CH3OH (30:1))

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

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

Procedure: To a suspension of 866 mg (5.0 mmol.) of quinaldinic acid and 576 mg (5.0 mmol.) of 1-hydroxysuccinimide in 20 ml of ethyl acetate was dropwise added over a period of 5-10 min. under chilling with ice a solution of 1.09 g (5.0 mmol.) of N,N'-dicyclohexylcarbodiimide. After the addition was complete, the mixture was stirred for 2 hours at room temperature. To this mixture was dropwise added a solution of 1.09 g (5.0 mmol.) of 1-(3-amino-3-phenylpropyl)piperidine in 5 ml of ethyl acetate. After the addition was complete, the mixture was stirred overnight at room temperature. Precipitated insolubles were filtered off and then the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution. The mixture was then dried over sodium sulfate, and was evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (silica gel: 20 g, CHCl3 and CHCl3 /CH3OH (30:1)) to obtain 1.72 g (yield: 92%) of the subject compound as a pale yellow crystalline product. was dropwise added over a period of 5-10 min. After the addition After the addition the mixture was stirred overnight at room temperature Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution The mixture was then dried over sodium sulfate was evaporated under reduced pressure to remove the solvent The residue was purified by silica gel column chromatography (silica gel: 20 g, CHCl3 and CHCl3 /CH3OH (30:1))

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

Procedure: To a solution of 1.73 g (10 mmol.) of quinaldinic acid and 1.53 g (10 mmol.) of 1-hydroxybenzotriazole monohydrate in 50 ml of ethyl acetate was dropwise added over a period of 20 min. under chilling with ice a solution of 2.06 g (10 mmol.) of N,N'-dicyclohexylcarbodiimide in 10 ml of ethyl acetate. After the addition was complete, the resulting mixture was stirred for 2 hours at room temperature and chilled with ice. To the chilled mixture was dropwise added over a period of 30 min. a solution of 2.18 g (10 mmol.) of 1-(3-amino-3-phenylpropyl)piperidine in 8 ml of ethyl acetate. After the addition was complete, the mixture was stirred overnight at room temperature. Precipitated insolubles were filtered off and then the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution. The mixture was then dried over sodium sulfate, and was evaporated under reduced pressure to remove the solvent. The residue was crystallized after addition of n-hexane. The resulting crystals were washed three times with n-hexane and dissolved in 35 ml of ethyl acetate. The resulting solution was allowed to stand overnight in a refrigerator. Precipitated insolubles were filtered off and the insolubles were washed with ethyl acetate. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (silica gel: 40 g, CHCl3 and CHCl3 /CH3OH (30:1)) to obtain 3.07 g (yield: 82%) of the subject compound as a pale yellow crystalline product. After the addition chilled with ice After the addition the mixture was stirred overnight at room temperature Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate washed twice with a saturated aqueous sodium hydrogencarbonate solution and once with a saturated aqueous sodium chloride solution The mixture was then dried over sodium sulfate was evaporated under reduced pressure to remove the solvent The residue was crystallized after addition of n-hexane The resulting crystals were washed three times with n-hexane dissolved in 35 ml of ethyl acetate to stand overnight in a refrigerator Precipitated insolubles were filtered off the insolubles were washed with ethyl acetate concentrated under reduced pressure The residue was purified by silica gel column chromatography (silica gel: 40 g, CHCl3 and CHCl3 /CH3OH (30:1))

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

Procedure: The procedure given in Example 2 except for the formation of salts was followed using 3-bromo-1-(tert-butoxycarbonyl)amino-1-phenyl propane and piperidine as reactants, instead of d-1-bromo-2-(tert-butoxycarbonyl)amino-3-phenyl propane and hexamethyleneimine to give 1-Phenyl-3-(1-piperidinyl)-n-propylamine.