(4-benzylpiperazin-1-yl)-piperidin-4-ylmethanone

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of l-benzyl-4-[1-(t-butoxycarbonyl)-4-piperidylcarbonyl]piperazine (115.7 g) in dry dichloromethane (222 ml) was added dropwise over 45 minutes to trifluoroacetic acid (575 ml), maintaining the temperature below 25° C. under an atmosphere of argon. The solution was stirred at 23-25° C. for 1 hour. The solution was evaporated using a bath temperature of 30° C. The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C. The aqueous mixture was extracted with dichloromethane (3×575 ml). The dichloromethane extracts were combined, dried (Na2SO4) and evaporated to give 1-benzyl-4-(4-piperidylcarbonyl)piperazine (56.2 g, 65% yield) as a colourless solid; maintaining the temperature below 25° C. under an atmosphere of argon The solution was evaporated temperature of 30° C The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C The aqueous mixture was extracted with dichloromethane (3×575 ml) dried (Na2SO4) evaporated

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of l-benzyl-4-[1-(t-butoxycarbonyl)-4-piperidylcarbonyl]piperazine (115.7 g) in dry dichloromethane (222 ml) was added dropwise over 45 minutes to trifluoroacetic acid (575 ml), maintaining the temperature below 25° C. under an atmosphere of argon. The solution was stirred at 23-25° C. for 1 hour. The solution was evaporated using a bath temperature of 30° C. The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C. The aqueous mixture was extracted with dichloromethane (3×575 ml). The dichloromethane extracts were combined, dried (Na2SO4) and evaporated to give 1-benzyl-4-(4-piperidylcarbonyl)piperazine (56.2 g, 65% yield) as a colourless solid; maintaining the temperature below 25° C. under an atmosphere of argon The solution was evaporated temperature of 30° C The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C The aqueous mixture was extracted with dichloromethane (3×575 ml) dried (Na2SO4) evaporated

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

実験手順: 4-Chloropyrimidine hydrochloride (3.5 g) was added to a stirred suspension of 1-benzyl-4-[4-piperidylcarbonyl]piperazine (6.6 g), triethylamine (12.8 ml) and ethanol (120 ml). The mixture was heated under reflux for four hours and evaporated in vacuo to yield a treacle like substance. The residue was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (Na2SO4) and evaporated. The residue was absorbed onto alumina and purified using dry flash chromatography eluting with increasingly polar mixtures of dichloromethane and methanol (1:0 to 98:2). The material obtained was triturated with diethylether to give 1-(benzyl)-4-[1 -(4-pyrimidinyl)-4-piperidylcarbonyl]piperazine (3.8 g, 45% yield), mp 107-108.5° C.; The mixture was heated under reflux for four hours evaporated in vacuo to yield a treacle like substance The residue was partitioned between ethyl acetate and water The organic phase was washed with brine dried (Na2SO4) evaporated The residue was absorbed onto alumina purified using dry flash chromatography eluting with increasingly polar mixtures of dichloromethane and methanol (1:0 to 98:2) The material obtained was triturated with diethylether

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-benzyl-4-[(1-t-butoxycarbonyl-4-piperidyl)carbonyl]piperazine (115.7 g) in dry dichloromethane (222 ml) was added dropwise over 45 minutes to trifluoroacetic acid (575 ml), maintaining the temperature below 25° C. under an atmosphere of argon. The solution was stirred at 23-25° C. for 1 hour. The solution was evaporated using a bath temperature of 30° C. The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C. The aqueous mixture was extracted with dichloromethane (3×575 ml). The dichloromethane extracts were combined, dried (Na2SO4) and evaporated to give 1-benzyl-4-[(4-piperidyl)carbonyl]piperazine (56.2 g, 65% yield) as a white solid; maintaining the temperature below 25° C. under an atmosphere of argon The solution was evaporated temperature of 30° C The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C The aqueous mixture was extracted with dichloromethane (3×575 ml) dried (Na2SO4) evaporated

反応条件: temp:24.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-benzyl-4-[(1-t-butoxycarbonyl-4-piperidyl)carbonyl]piperazine (115.7 g) in dry dichloromethane (222 ml) was added dropwise over 45 minutes to trifluoroacetic acid (575 ml), maintaining the temperature below 25° C. under an atmosphere of argon. The solution was stirred at 23-25° C. for 1 hour. The solution was evaporated using a bath temperature of 30° C. The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C. The aqueous mixture was extracted with dichloromethane (3×575 ml). The dichloromethane extracts were combined, dried (Na2SO4) and evaporated to give 1-benzyl-4-[(4-piperidyl)carbonyl]piperazine (56.2 g, 65% yield) as a white solid; maintaining the temperature below 25° C. under an atmosphere of argon The solution was evaporated temperature of 30° C The residual oil was poured, in portions, into saturated aqueous sodium carbonate solution (770 ml) while maintaining the temperature below 30° C The aqueous mixture was extracted with dichloromethane (3×575 ml) dried (Na2SO4) evaporated