1-propylpiperidin-2-one

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography

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

実験手順: A solution of 1-propyl-2-piperidone (50 mM) in benzene (40 ml) was added dropwise to a solution of lithium di-isopropylamide [ex n-butyl lithium in hexane (32.3 ml, 50 mM), di-isopropylamine (7 ml, 50 mM) and THF (33 ml)]. A solution of 2-bromo-3-methoxycyclohex-2-en-1-one (10.25 g, 50 mM) in THF (40 ml) was added, and after 5 minutes the mixture was quenched by pouring on to excess aqueous hydrochloric acid. Ether extraction followed by passage through a short silica pad using ethyl acetate as eluant gave the title compound as a colourless oil (10.75 g). after 5 minutes the mixture was quenched by pouring on to excess aqueous hydrochloric acid Ether extraction

反応条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To N-propyl-2-piperidone (1.92 g) was added a 4 N aqueous sodium hydroxide solution (6.8 ml), and the mixture was refluxed at 115° C. for 5 hours. Thereto was added concentrated hydrochloric acid (2.27 ml) at 0° C. to neutralize the resulting mixture. Then, sodium carbonate (2.88 g), water (11.5 ml) and DMSO (18.2 ml) were added thereto. After the mixture was heated to 90° C., a solution of 5-bromo-2-chloronicotinaldehyde (1.5 g) in DMSO (23 ml) was added dropwise thereto and the mixture was stirred as it is for 2 hours. After cooling to 0° C., water was added thereto. 6 N Hydrochloric acid (9 ml) was then added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the residue as it is was dissolved in DMF (50 ml), and then potassium carbonate (2.31 g) and iodomethane (1.04 ml) were added thereto. The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. Water was added thereto and the mixture was then extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→hexane:ethyl acetate=4:1) to give methyl 5-[(5-bromo-3-formylpyridin-2-yl)(propyl)amino]pentanoate (909 mg) as a yellow oily material. After the mixture was heated to 90° C. After cooling to 0° C. the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was distilled off under reduced pressure the residue as it is was dissolved in DMF (50 ml) potassium carbonate (2.31 g) and iodomethane (1.04 ml) were added The mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours Water was added the mixture was then extracted with ethyl acetate The organic layer was washed with saturated brine dried over magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→hexane:ethyl acetate=4:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-propyl-2-piperidone (7.5 g) and 4N sodium hydroxide (26.6 ml) was refluxed for 4 hours. The mixture was cooled to 0° C. and conc. hydrochloric acid (8.85 ml) was added thereto. To the mixture were added sodium carbonate (11.3 g), 5-bromo-2-fluorobenzaldehyde (5.4 g) and DMSO (70 ml), and the resulting mixture was heated at 135° C. for 6 hours. The mixture was allowed to cool. Water was added and the mixture was extracted with THF-ethyl acetate. The organic layer was washed with water and saturated saline, and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain brown oil of 5-(4-bromo-2-formyl-N-propylanilino)pentanoic acid (8.8 g) was refluxed for 4 hours the resulting mixture was heated at 135° C. for 6 hours to cool the mixture was extracted with THF-ethyl acetate The organic layer was washed with water and saturated saline dried over magnesium sulfate After distilling off the solvent under reduced pressure the residue was purified by silica gel column chromatography