1-benzyl-3,5-dimethylpiperidin-4-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-benzyl-3-methyl-4-piperidone (2.0 g, 9.8 mmol) in THF at about −78° C. under argon, was added Lithium diisopropylamide (7.35 mL, 14.7 mmol, 2 M in heptane/THF/ethylbenzene). After stirring for about 1 hour at about −78° C., iodomethane (0.73 mL, 11.8 mmol) was added. The reaction mixture was stirred for about 1 hour at about −78° C., then warmed to room temperature. Stirring was continued overnight at room temperature. The reaction was quenched with saturated ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with water, then brine and dried over magnesium sulfate. The crude product was chromatographed on silica gel, eluting with EtOAc/hexane (3:10) to give a yellow oil of the title compound. The reaction mixture was stirred for about 1 hour at about −78° C. warmed to room temperature Stirring was continued overnight at room temperature The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The organic layer was washed with water brine and dried over magnesium sulfate The crude product was chromatographed on silica gel eluting with EtOAc/hexane (3:10)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-benzyl-3-methyl-4-piperidone (2.0 g, 9.8 mmol) in THF at about −78° C. under argon, was added Lithium diisopropylamide (7.35 mL, 14.7 mmol, 2 M in heptane/THF/ethylbenzene). After stirring for about 1 hour at about −78° C., iodomethane (0.73 mL, 11.8 mmol) was added. The reaction mixture was stirred for about 1 hour at about −78° C., then warmed to room temperature. Stirring was continued overnight at room temperature. The reaction was quenched with saturated ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with water, then brine and dried over magnesium sulfate. The crude product was chromatographed on silica gel, eluting with EtOAc/hexane (3:10) to give a yellow oil of the title compound. The reaction mixture was stirred for about 1 hour at about −78° C. warmed to room temperature Stirring was continued overnight at room temperature The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The organic layer was washed with water brine and dried over magnesium sulfate The crude product was chromatographed on silica gel eluting with EtOAc/hexane (3:10)

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

実験手順: Ethyl chloroformate (10.0 g, 90 mmol) was added to a stirred solution of 1-benzyl-3,5-dimethyl-4-piperidinone (5.0 g, 24 mmol) in benzene (20 ml), refluxed with stirring for 6 hr and concentrated to dryness to give 1-carbethoxy-3,5-dimethyl-4-piperidinone as oil. refluxed concentrated to dryness

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-benzyl-3-methyl-4-piperidone (2.0 g, 9.8 mmol) in THF at about −78° C. under argon, was added Lithium diisopropylamide (7.35 mL, 14.7 mmol, 2 M in heptane/THF/ethylbenzene). After stirring for about 1 hour at about −78° C., iodomethane (0.73 mL, 11.8 mmol) was added. The reaction mixture was stirred for about 1 hour at about −78° C., then warmed to room temperature. Stirring was continued overnight at room temperature. The reaction was quenched with saturated ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with water, then brine and dried over magnesium sulfate. The crude product was chromatographed on silica gel, eluting with EtOAc/hexane (3:10) to give a yellow oil of the title compound. The reaction mixture was stirred for about 1 hour at about −78° C. warmed to room temperature Stirring was continued overnight at room temperature The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The organic layer was washed with water brine and dried over magnesium sulfate The crude product was chromatographed on silica gel eluting with EtOAc/hexane (3:10)

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

実験手順: Ethyl chloroformate (10.0 g, 90 mmol) was added to a stirred solution of 1-benzyl-3,5-dimethyl-4-piperidinone (5.0 g, 24 mmol) in benzene (20 ml), refluxed with stirring for 6 hr and concentrated to dryness to give 1-carbethoxy-3,5-dimethyl-4-piperidinone as oil. Yield 4.51 g (90%), C10H17NO3, m/z 200 (M+1). refluxed concentrated to dryness

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a −78° C. solution of 1-benzyl-3-methyl-piperidin-4-one (4.06 g, 20 mmol) in anhydrous THF (20 mL) was added lithium hexamethyldisilazide (21 mL, 21 mmol of a 1.0 M solution THF). After being stirred at −78° C. for 30 min, a solution of iodomethane (1.31 mL, 21 mmol) in THF (5 mL) was added into the reaction mixture. The resultant solution was stirred at 25° C. for 2 h and quenched with water. The aqueous layer was extracted with CH2Cl2. The organic extracts were combined, washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude product. The crude material was purified by flash column chromatography (hexane/EtOAc) to provide 1.37 g (31.5% yield) of 1-benzyl-3,5-dimethyl-piperidin-4-one. quenched with water The aqueous layer was extracted with CH2Cl2 washed with brine dried over MgSO4 The solution was filtered concentrated in vacuo to give the crude product The crude material was purified by flash column chromatography (hexane/EtOAc)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a −78° C. solution of 1-benzyl-3-methyl-piperidin-4-one (4.06 g, 20 mmol) in anhydrous THF (20 mL) was added lithium hexamethyldisilazide (21 mL, 21 mmol of a 1.0 M solution THF). After being stirred at −78° C. for 30 min, a solution of iodomethane (1.31 mL, 21 mmol) in THF (5 mL) was added into the reaction mixture. The resultant solution was stirred at 25° C. for 2 h and quenched with water. The aqueous layer was extracted with CH2Cl2. The organic extracts were combined, washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude product. The crude material was purified by flash column chromatography (hexane/EtOAc) to provide 1.37 g (31.5% yield) of 1-benzyl-3,5-dimethyl-piperidin-4-one. quenched with water The aqueous layer was extracted with CH2Cl2 washed with brine dried over MgSO4 The solution was filtered concentrated in vacuo to give the crude product The crude material was purified by flash column chromatography (hexane/EtOAc)