N-tert-butylpiperidine-4-carboxamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to −5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C. reaction temperature between 0 and 5° C to warm to room temperature The layers were separated the aqueous layer was extracted with dichloromethane (200 mL) The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes The slurry was filtered the filter cake was washed with 100 mL of hexanes dried in a vacuum oven overnight at 50° C.

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to 5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C. reaction temperature between 0 and 5° C to warm to room temperature The layers were separated the aqueous layer was extracted with dichloromethane (200 mL) The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes The slurry was filtered the filter cake was washed with 100 mL of hexanes dried in a vacuum oven overnight at 50° C.

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to 5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C. reaction temperature between 0 and 5° C to warm to room temperature The layers were separated the aqueous layer was extracted with dichloromethane (200 mL) The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes The slurry was filtered the filter cake was washed with 100 mL of hexanes dried in a vacuum oven overnight at 50° C.

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to −5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C. reaction temperature between 0 and 5° C to warm to room temperature The layers were separated the aqueous layer was extracted with dichloromethane (200 mL) The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes The slurry was filtered the filter cake was washed with 100 mL of hexanes dried in a vacuum oven overnight at 50° C.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to −5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C. reaction temperature between 0 and 5° C to warm to room temperature The layers were separated the aqueous layer was extracted with dichloromethane (200 mL) The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes The slurry was filtered the filter cake was washed with 100 mL of hexanes dried in a vacuum oven overnight at 50° C.

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to −5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C. reaction temperature between 0 and 5° C to warm to room temperature The layers were separated the aqueous layer was extracted with dichloromethane (200 mL) The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes The slurry was filtered the filter cake was washed with 100 mL of hexanes dried in a vacuum oven overnight at 50° C.

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

実験手順: The title compound is prepared according to the reactions described above starting from 2-bromo-5-nitro-benzaldehyde and piperidine-4-carboxylic acid tert-butylamide yielding after reductive amination 1-(2-bromo-5-nitro-benzyl)-piperidine-4-carboxylic acid tert-butylamide; LC-MS A: tR=0.62 min; [M+H]+=397.99; followed by alkylation with ethylboronic acid yielding 1-(2-ethyl-5-nitro-benzyl)-piperidine-4-carboxylic acid tert-butylamide; LC-MS A: tR=0.66 min; [M+H]+=348.34, followed by reduction with stannous chloride the title compound; LC-MS A: tR=0.49 min; [M+H]+=318.21.

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

実験手順: The title compound is prepared according to the reactions described for BB-5 above starting from 4-ethyl-3-nitro-benzaldehyde and piperidine-4-carboxylic acid tert-butylamide yielding after reductive amination 1-(4-ethyl-3-nitro-benzyl)-piperidine-4-carboxylic acid tert-butylamide; LC-MS A: tR=0.67 min; [M+H]+=348.18 followed by reduction with stannous chloride the title compound; LC-MS A: tR=0.53 min; [M+H]+=318.22. The title compound is prepared

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

実験手順: The title compound is prepared according to the reactions described for BB-5 above starting from 3-methoxy-5-nitro-benzaldehyde and piperidine-4-carboxylic acid tert-butylamide yielding after reductive amination 1-(3-methoxy-5-nitro-benzyl)-piperidine-4-carboxylic acid tert-butylamide; LC-MS A: tR=0.63 min; [M+H]+=350.14 followed by reduction with stannous chloride the title compound; LC-MS A: tR=0.50 min; [M+H]+=320.19. The title compound is prepared

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

実験手順: The title compound is prepared according to the reactions described for BB-5 above starting from 2-methoxy-3-nitro-benzaldehyde and piperidine-4-carboxylic acid tert-butylamide yielding after reductive amination 1-(2-methoxy-3-nitro-benzyl)-piperidine-4-carboxylic acid tert-butylamide; LC-MS A: tR=0.61 min; [M+H]+=350.22 followed by reduction with stannous chloride the title compound; LC-MS A: tR=0.52 min; [M+H]+=320.27. The title compound is prepared