N-(1-benzyl-4-methylpiperidin-4-yl)acetamide

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:; See reaction.notes.procedure_details.

実験手順: 39.4 g of 4-acetylamino-1-benzyl-4-methylpiperidine are heated to boiling in 400 ml of concentrated hydrochloric acid for 3 days. After evaporation to half the volume in a rotary evaporator, the pH is adjusted to 12 with 50% strength sodium hydroxide solution while cooling. The mixture is extracted three times with methylene chloride. The combined organic phases are then dried over sodium sulphate, and the solvent is distilled off in a rotary evaporator. The residue is employed without further purification in the next reaction. After evaporation to half the volume in a rotary evaporator while cooling The mixture is extracted three times with methylene chloride The combined organic phases are then dried over sodium sulphate the solvent is distilled off in a rotary evaporator The residue is employed without further purification in the next reaction

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

実験手順: A mixture of N-(1-benzyl-4-methyl-4-piperidinyl)acetamide obtained in Example 10-2 (3.45 g) and conc. HCl (41 mL) was heated under reflux with stirring for 72 hrs. After cooling, the mixture was quenched by adding 3N potassium hydroxide solution, and the resulting solution (pH11) was extracted with chloroform. The organic layer was washed with brine, dried over MgSO4, and concentrated to give the title compound as a pale brown oil (2.86 g). was heated under reflux After cooling the mixture was quenched by adding 3N potassium hydroxide solution the resulting solution (pH11) was extracted with chloroform The organic layer was washed with brine dried over MgSO4 concentrated

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-benzyl-4-methyl-4-piperidinol obtained in Example 10-1 (3.34 g) in acetonitrile (19 mL) was added dropwise conc. sulfuric acid (16 mL) with cooling on an ice bath. The mixture was warmed to 20° C. and stirred for 15 hrs. After cooling, the reaction mixture was quenched by adding 3N potassium hydroxide solution, and the resulting solution (pH9) was extracted with ethyl acetate three times. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated. The residual solid was triturated with ether to give the title compound as a white powder (3.55 g). with cooling on an ice bath After cooling the reaction mixture was quenched by adding 3N potassium hydroxide solution the resulting solution (pH9) was extracted with ethyl acetate three times The combined organic extracts were washed with brine dried over MgSO4 concentrated The residual solid was triturated with ether

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

実験手順: 39.4 g of 4-acetylamino-1-benzyl-4-methylpiperidine are heated to boiling in 400 ml of concentrated hydrochloric acid for 3 days. After evaporation to half the volume in a rotary evaporator, the pH is adjusted to 12 with 50% strength sodium hydroxide solution while cooling. The mixture is extracted three times with methylene chloride. The combined organic phases are then dried over sodium sulphate, and the solvent is distilled off in a rotary evaporator. The residue is employed without further purification in the next reaction. After evaporation to half the volume in a rotary evaporator while cooling The mixture is extracted three times with methylene chloride The combined organic phases are then dried over sodium sulphate the solvent is distilled off in a rotary evaporator The residue is employed without further purification in the next reaction

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

実験手順: 39.4 g of 4-acetylamino-1-benzyl-4-methylpiperidine are heated to boiling in 400 ml of concentrated hydrochloric acid for 3 days. After evaporation to half the volume in a rotary evaporator, the pH is adjusted to 12 with 50% strength sodium hydroxide solution while cooling. The mixture is extracted three times with methylene chloride. The combined organic phases are then dried over sodium sulphate, and the solvent is distilled off in a rotary evaporator. The residue is employed without further purification in the next reaction. After evaporation to half the volume in a rotary evaporator while cooling The mixture is extracted three times with methylene chloride The combined organic phases are then dried over sodium sulphate the solvent is distilled off in a rotary evaporator The residue is employed without further purification in the next reaction

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:; See reaction.notes.procedure_details.

実験手順: Concentrated sulphuric acid (3 ml) was added dropwise to a solution of 1-benzyl-4-methyl-4-piperidinol (640 mg, 2.56 mmol) in acetonitrile (4 ml) at 0° C. After 1 hour the reaction was cautiously poured onto 2N sodium hydroxide (20 ml), the layers separated and the aqueous extracted with dichloromethane (3×). The combined organic extracts were washed with water, brine, dried (K2CO3), filtered and evaporated under reduced pressure to afford the title compound as a clear oil, 600 mg. the layers separated the aqueous extracted with dichloromethane (3×) The combined organic extracts were washed with water, brine dried (K2CO3) filtered evaporated under reduced pressure

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

実験手順: A mixture of N-(1-benzyl-4-methyl-4-piperidinyl)acetamide obtained in Example 10-2 (3.45 g) and conc. HCl (41 mL) was heated under reflux with stirring for 72 hrs. After cooling, the mixture was quenched by adding 3N potassium hydroxide solution, and the resulting solution (pH11) was extracted with chloroform. The organic layer was washed with brine, dried over MgSO4, and concentrated to give the title compound as a pale brown oil (2.86 g). was heated under reflux After cooling the mixture was quenched by adding 3N potassium hydroxide solution the resulting solution (pH11) was extracted with chloroform The organic layer was washed with brine dried over MgSO4 concentrated

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-benzyl-4-methyl-4-piperidinol obtained in Example 10-1 (3.34 g) in acetonitrile (19 mL) was added dropwise conc. sulfuric acid (16 mL) with cooling on an ice bath. The mixture was warmed to 20° C. and stirred for 15 hrs. After cooling, the reaction mixture was quenched by adding 3N potassium hydroxide solution, and the resulting solution (pH9) was extracted with ethyl acetate three times. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated. The residual solid was triturated with ether to give the title compound as a white powder (3.55 g). with cooling on an ice bath After cooling the reaction mixture was quenched by adding 3N potassium hydroxide solution the resulting solution (pH9) was extracted with ethyl acetate three times The combined organic extracts were washed with brine dried over MgSO4 concentrated The residual solid was triturated with ether