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.
