ethyl 1-benzyl-3-methyl-4-oxopiperidine-3-carboxylate

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl-1-benzyl-3-methyl-4-oxo-piperidine-3-carboxylate (85 g, 0.31 mol) was dissolved in conc HCl (82 ml, 0.77 mol) and the reaction mixture was heated to 100° C. for 32 hrs. Solvent was removed under reduced pressure and the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to this under stirring to provide a solid. The solid was filter and was dissolved in 400 ml ethyl acetate and organic layer was washed with 10% NaOH aqueous solution. Layers were separated and concentration of organic layer afforded 48 g (75%) oil as a titled product. Solvent was removed under reduced pressure the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to to provide a solid The solid was filter was dissolved in 400 ml ethyl acetate organic layer was washed with 10% NaOH aqueous solution Layers were separated

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl-1-benzyl-3-methyl-4-oxo-piperidine-3-carboxylate (85 g, 0.31 mol) was dissolved in conc HCl (82 ml, 0.77 mol) and the reaction mixture was heated to 100° C. for 32 hrs. Solvent was removed under reduced pressure and the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to this under stirring to provide a solid. The solid was filter and was dissolved in 400 ml ethyl acetate and organic layer was washed with 10% NaOH aqueous solution. Layers were separated and concentration of organic layer afforded 48 g (75%) oil as a titled product. Solvent was removed under reduced pressure the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to to provide a solid The solid was filter was dissolved in 400 ml ethyl acetate organic layer was washed with 10% NaOH aqueous solution Layers were separated

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

実験手順: Ethyl-1-benzyl-4-oxo-piperidine-3-carboxylate hydrochloride (150 g, 0.504 mol) was suspended in a solvent mixture of 750 ml THF and 750 ml DMF at room temperature. Addition of powdered KOH (56 g, 1.0 mol) was made in two equal lots keeping half an hour interval between two additions. To a clear reaction mixture methyl iodide (78 g, 0.55 mol) was added over period of 10 minutes and it was stirred for three hours at room temperature. The reaction was quenched by adding 4 ltr water followed by 1.5 ltr diethyl ether. Layers were separated. Organic layer was washed with water and dried over Na2SO4. Evaporation of organic solvent afforded a liquid, which was passed through a silica gel column to give 86 g (61%), titled compound. keeping half an hour The reaction was quenched by adding 4 ltr water Layers were separated Organic layer was washed with water dried over Na2SO4 Evaporation of organic solvent afforded a liquid, which

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl-1-benzyl-3-methyl-4-oxo-piperidine-3-carboxylate (85 g, 0.31 mol) was dissolved in conc HCl (82 ml, 0.77 mol) and the reaction mixture was heated to 100° C. for 32 hrs. Solvent was removed under reduced pressure and the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to this under stirring to provide a solid. The solid was filter and was dissolved in 400 ml ethyl acetate and organic layer was washed with 10% NaOH aqueous solution. Layers were separated and concentration of organic layer afforded 48 g (75%) oil as a titled product. Solvent was removed under reduced pressure the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to to provide a solid The solid was filter was dissolved in 400 ml ethyl acetate organic layer was washed with 10% NaOH aqueous solution Layers were separated

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

実験手順: Ethyl -1-benzyl-4-oxo-piperidine-3-carboxylate hydrochloride (150 g, 0.504 mol) was suspended in a solvent mixture of 750 ml THF and 750 ml DMF at room temperature. Addition of powdered KOH (56 g, 1.0 mol) was made in two equal lots keeping half an hour interval between two additions. To a clear reaction mixture methyl iodide (78 g, 0.55 mol) was added over period of 10 minutes and it was stirred for three hours at room temperature. The reaction was quenched by adding 4 ltr water followed by 1.5 ltr diethyl ether. Layers were separated. Organic layer was washed with water and dried over Na2SO4. Evaporation of organic solvent afforded a liquid, which was passed through a silica gel column to give 86 g (61%), titled compound. keeping half an hour The reaction was quenched by adding 4 ltr water Layers were separated Organic layer was washed with water dried over Na2SO4 Evaporation of organic solvent afforded a liquid, which

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

実験手順: Ethyl -1-benzyl-4-oxo-piperidine-3-carboxylate hydrochloride (150 g, 0.504 mol) was suspended in a solvent mixture of 750 ml THF and 750 ml DMF at room temperature. Addition of powdered KOH (56 g, 1.0 mol) was made in two equal lots keeping half an hour interval between two additions. To a clear reaction mixture methyl iodide (78 g, 0.55 mol) was added over period of 10 minutes and it was stirred for three hours at room temperature. The reaction was quenched by adding 4 ltr water followed by 1.5 ltr diethyl ether. Layers were separated. Organic layer was washed with water and dried over Na2SO4. Evaporation of organic solvent afforded a liquid, which was passed through a silica gel column to give 86 g (61%), titled compound. keeping half an hour The reaction was quenched by adding 4 ltr water Layers were separated Organic layer was washed with water dried over Na2SO4 Evaporation of organic solvent afforded a liquid, which

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl-1-benzyl-3-methyl-4-oxo-piperidine-3-carboxylate (85 g, 0.31 mol) was dissolved in conc HCl (82 ml, 0.77 mol) and the reaction mixture was heated to 100° C. for 32 hrs. Solvent was removed under reduced pressure and the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to this under stirring to provide a solid. The solid was filter and was dissolved in 400 ml ethyl acetate and organic layer was washed with 10% NaOH aqueous solution. Layers were separated and concentration of organic layer afforded 48 g (75%) oil as a titled product. Solvent was removed under reduced pressure the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to to provide a solid The solid was filter was dissolved in 400 ml ethyl acetate organic layer was washed with 10% NaOH aqueous solution Layers were separated

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

実験手順: Ethyl-1-benzyl-4-oxo-piperidine-3-carboxylate hydrochloride (150 g, 0.504 mol) was suspended in a solvent mixture of 750 ml THF and 750 ml DMF at room temperature. Addition of powdered KOH (56 g, 1.0 mol) was made in two equal lots keeping half an hour interval between two additions. To a clear reaction mixture methyl iodide (78 g, 0.55 mol) was added over period of 10 minutes and it was stirred for three hours at room temperature. The reaction was quenched by adding 4 ltr water followed by 1.5 ltr diethyl ether. Layers were separated. Organic layer was washed with water and dried over Na2SO4. Evaporation of organic solvent afforded a liquid, which was passed through a silica gel column to give 86 g (61%), titled compound. keeping half an hour The reaction was quenched by adding 4 ltr water Layers were separated Organic layer was washed with water dried over Na2SO4 Evaporation of organic solvent afforded a liquid, which

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

実験手順: To a suspension of ethyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride (20 g, 67.2 mmol) in THF (130 mL)/DMF (130 mL) was added KOH (powder, 7.64 g, 136 mmol) at room temperature. The reaction mixture was stirred for 5-10 min, then added iodomethane (4.62 mL, 73.9 mmol) dropwise. The reaction mixture was further stirred for 3 h at room temperature and then quenched with water. The aqueous phase was extracted with diethyl ether twice. The organic phases were combined and washed with water, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (0-20% EtOAc/heptanes) to provide ethyl 1-benzyl-3-methyl-4-oxopiperidine-3-carboxylate. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.15-7.45 (m, 5H), 4.00-4.21 (m, 2H), 3.66 (d, J=13.39 Hz, 1H), 3.47 (d, J=13.39 Hz, 1H), 3.30 (dd, J=2.78, 11.62 Hz, 1H), 2.96-3.08 (m, 1H), 2.77 (ddd, J=6.69, 11.68, 14.46 Hz, 1H), 2.36-2.45 (m, 1H), 2.27-2.35 (m, 1H), 2.14 (d, J=11.37 Hz, 1H), 1.15 (t, J=7.07 Hz, 3H), 1.09 (s, 3H). The reaction mixture was further stirred for 3 h at room temperature quenched with water The aqueous phase was extracted with diethyl ether twice washed with water dried over Na2SO4 filtered concentrated The resulting residue was purified by silica gel flash chromatography (0-20% EtOAc/heptanes)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl-1-benzyl-3-methyl-4-oxo-piperidine-3-carboxylate (85 g, 0.31 mol) was dissolved in conc HCl (82 ml, 0.77 mol) and the reaction mixture was heated to 100° C. for 32 hrs. Solvent was removed under reduced pressure and the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to this under stirring to provide a solid. The solid was filter and was dissolved in 400 ml ethyl acetate and organic layer was washed with 10% NaOH aqueous solution. Layers were separated and concentration of organic layer afforded 48 g (75%) oil as a titled product. Solvent was removed under reduced pressure the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to to provide a solid The solid was filter was dissolved in 400 ml ethyl acetate organic layer was washed with 10% NaOH aqueous solution Layers were separated

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

実験手順: Ethyl-1-benzyl-4-oxo-piperidine-3-carboxylate hydrochloride (150 g, 0.504 mol) was suspended in a solvent mixture of 750 ml THF and 750 ml DMF at room temperature. Addition of powdered KOH (56 g, 1.0 mol) was made in two equal lots keeping half an hour interval between two additions. To a clear reaction mixture methyl iodide (78 g, 0.55 mol) was added over period of 10 minutes and it was stirred for three hours at room temperature. The reaction was quenched by adding 4 ltr water followed by 1.5 ltr diethyl ether. Layers were separated. Organic layer was washed with water and dried over Na2SO4. Evaporation of organic solvent afforded a liquid, which was passed through a silica gel column to give 86 g (61%), titled compound. keeping half an hour The reaction was quenched by adding 4 ltr water Layers were separated Organic layer was washed with water dried over Na2SO4 Evaporation of organic solvent afforded a liquid, which

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl-1-benzyl-3-methyl-4-oxo-piperidine-3-carboxylate (85 g, 0.31 mol) was dissolved in conc HCl (82 ml, 0.77 mol) and the reaction mixture was heated to 100° C. for 32 hrs. Solvent was removed under reduced pressure and the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to this under stirring to provide a solid. The solid was filter and was dissolved in 400 ml ethyl acetate and organic layer was washed with 10% NaOH aqueous solution. Layers were separated and concentration of organic layer afforded 48 g (75%) oil as a titled product. Solvent was removed under reduced pressure the resulting solid was dissolved in the 300 ml CHCl3 and 400 ml pet ether was added to to provide a solid The solid was filter was dissolved in 400 ml ethyl acetate organic layer was washed with 10% NaOH aqueous solution Layers were separated