1-(3-phenylpropyl)piperidin-4-amine

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: While 39.11 g (0.1792 mol) of 5-thia-1,8b-diazaacenaphthylene-4-carboxylic acid and 21.7 g (0.188 mol) of N-hydroxysuccinimide were stirred together in 500 ml of acetonitrile, 36.1 g (0.188 mol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added, and the mixture was stirred at room temperature overnight. To this reaction mixture was added 30.0 ml (0.215 mol) of triethylamine and, then, a solution of 39.1 g (0.179 mol) of 4-amino-1-(3-phenylpropan-1-yl)piperidine in acetonitrile (100 ml)-chloroform (50 ml) was added. The mixture was stirred at room temperature for 1 hour and the resulting orange-colored precipitate was recovered by filtration and rinsed with acetonitrile (yield 55.75 g). This crude product was purified by silica gel column chromatography (ethyl acetate to ethyl acetate/methanol : 4/1˜1/1) and recrystallization from chloroform-ethanol to provide the title compound. The mixture was stirred at room temperature for 1 hour the resulting orange-colored precipitate was recovered by filtration rinsed with acetonitrile (yield 55.75 g) This crude product was purified by silica gel column chromatography (ethyl acetate to ethyl acetate/methanol : 4/1˜1/1) and recrystallization from chloroform-ethanol

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

Procedure: To a mixture of 3.2 g of 5-hydroxy-2-methylindole-3-carboxylic acid and 3.7 g of 4-amino-1-(3-phenylpropyl)piperidine in 60 ml of tetrahydrofuran was added 3.8 g of dicyclohexylcarbodiimide, and the whole mixture was refluxed for 2 hours. After cooling, the precipitated dicyclohexylurea was filtered off and the filtrate was concentrated. The residue was crystallized from ethyl acetate. The crystals were filtered with suction, and recrystallized from a mixture of ethyl acetate and methanol to give 5-hydroxy-2-methyl-N-[1-(3-phenylpropyl)-4-piperidyl]indole-3-carboxamide, melting at 181°-184° C. The compound was precipitated as a monohydrate at first, but the water of crystallization was evaporated by vacuum drying over 3 hours at 90° C. the whole mixture was refluxed for 2 hours After cooling the precipitated dicyclohexylurea was filtered off the filtrate was concentrated The residue was crystallized from ethyl acetate The crystals were filtered with suction recrystallized from a mixture of ethyl acetate and methanol