1-[(4-bromophenyl)methyl]piperidin-4-amine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo benzylbromide (1.0 g, 4.1 mmol) in dichloromethane (20 ml) and diisopropyletylamine (1 ml) was added tert-butyl 4-piperidinylcarbamate (1.0 g, 5.0 mmol). The solution was then stirred at room temperature over night. The solvent was evaporated and 25 ml of 50% TFA in dichloromethane was added to the resulting white solid. The mixture was then stirred at room temperature for 2 h and then evaporated to dryness. The resulting solid was dissolved in water and extracted with toluene. After removal of the toluene the water phase was made basic with 1M NaOH giving a pH of 13. The water phase was then extracted with dichloromethane 3 times and the combined extracts were dried and then evaporated to give the pure product as a slightly yellow oil (0.96 g, 3.6 mmol) The solvent was evaporated 25 ml of 50% TFA in dichloromethane was added to the resulting white solid The mixture was then stirred at room temperature for 2 h evaporated to dryness The resulting solid was dissolved in water extracted with toluene After removal of the toluene the water phase The water phase was then extracted with dichloromethane 3 times the combined extracts were dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo benzylbromide (1.0 g, 4.1 mmol) in dichloromethane (20 ml) and diisopropyletylamine (1 ml) was added tert-butyl 4-piperidinylcarbamate (1.0 g, 5.0 mmol). The solution was then stirred at room temperature over night. The solvent was evaporated and 25 ml of 50% TFA in dichloromethane was added to the resulting white solid. The mixture was then stirred at room temperature for 2 h and then evaporated to dryness. The resulting solid was dissolved in water and extracted with toluene. After removal of the toluene the water phase was made basic with 1M NaOH giving a pH of 13. The water phase was then extracted with dichloromethane 3 times and the combined extracts were dried and then evaporated to give the pure product as a slightly yellow oil (0.96 g, 3.6 mmol) The solvent was evaporated 25 ml of 50% TFA in dichloromethane was added to the resulting white solid The mixture was then stirred at room temperature for 2 h evaporated to dryness The resulting solid was dissolved in water extracted with toluene After removal of the toluene the water phase The water phase was then extracted with dichloromethane 3 times the combined extracts were dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Reaction of a mixture of 4-chloro-5-sulfamoylphthalimide (6.48 g., 0.025 mole) and 4-amino-1-(4-bromobenzyl)piperidine (6.7 g., 0.025 mole) in n-pentanol according to the procedure of Example 1(a) afforded the 1,3-dioxoisoindole product. Purification of the crude product by triturating with n-heptane and crystallization from DMF-methanol afforded 6.9 g. (54%) of 2-[1-[(4-bromophenyl)methyl]-4-piperidinyl]-6-chloro-2,3-dihydro-1,3-dioxo-1H-isoindole-5-sulfonamide, m.p. 246°-247° (dec.).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Reaction of a mixture of 4-chloro-5-sulfamoylphthalimide (6.48 g., 0.025 mole) and 4-amino-1-(4-bromobenzyl)piperidine (6.7 g., 0.025 mole) in n-pentanol according to the procedure of Example 1(a) afforded the 1,3-dioxoisoindole product. Purification of the crude product by triturating with n-heptane and crystallization from DMF-methanol afforded 6.9 g. (54%) of 2-[1-[(4-bromophenyl)methyl]-4-piperidinyl]-6-chloro-2,3-dihydro-1,3-dioxo-1H-isoindole-5-sulfonamide, m.p. 246°-247° (dec.).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo benzylbromide (1.0 g, 4.1 mmol) in dichloromethane (20 ml) and diisopropyletylamine (1 ml) was added tert-butyl 4-piperidinylcarbamate (1.0 g, 5.0 mmol). The solution was then stirred at room temperature over night. The solvent was evaporated and 25 ml of 50% TFA in dichloromethane was added to the resulting white solid. The mixture was then stirred at room temperature for 2 h and then evaporated to dryness. The resulting solid was dissolved in water and extracted with toluene. After removal of the toluene the water phase was made basic with 1M NaOH giving a pH of 13. The water phase was then extracted with dichloromethane 3 times and the combined extracts were dried and then evaporated to give the pure product as a slightly yellow oil (0.96 g, 3.6 mmol) The solvent was evaporated 25 ml of 50% TFA in dichloromethane was added to the resulting white solid The mixture was then stirred at room temperature for 2 h evaporated to dryness The resulting solid was dissolved in water extracted with toluene After removal of the toluene the water phase The water phase was then extracted with dichloromethane 3 times the combined extracts were dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo benzylbromide (1.0 g, 4.1 mmol) in dichloromethane (20 ml) and diisopropyletylamine (1 ml) was added tert-butyl 4-piperidinylcarbamate (1.0 g, 5.0 mmol). The solution was then stirred at room temperature over night. The solvent was evaporated and 25 ml of 50% TFA in dichloromethane was added to the resulting white solid. The mixture was then stirred at room temperature for 2 h and then evaporated to dryness. The resulting solid was dissolved in water and extracted with toluene. After removal of the toluene the water phase was made basic with 1M NaOH giving a pH of 13. The water phase was then extracted with dichloromethane 3 times and the combined extracts were dried and then evaporated to give the pure product as a slightly yellow oil (0.96 g, 3.6 mmol) The solvent was evaporated 25 ml of 50% TFA in dichloromethane was added to the resulting white solid The mixture was then stirred at room temperature for 2 h evaporated to dryness The resulting solid was dissolved in water extracted with toluene After removal of the toluene the water phase The water phase was then extracted with dichloromethane 3 times the combined extracts were dried evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Reaction of a mixture of 4-chloro-5-sulfamoylphthalimide (6.48 g., 0.025 mole) and 4-amino-1-(4-bromobenzyl)piperidine (6.7 g., 0.025 mole) in n-pentanol according to the procedure of Example 1(a) afforded the 1,3-dioxoisoindole product. Purification of the crude product by triturating with n-heptane and crystallization from DMF-methanol afforded 6.9 g. (54%) of 2-[1-[(4-bromophenyl)methyl]-4-piperidinyl]-6-chloro-2,3-dihydro-1,3-dioxo-1H-isoindole-5-sulfonamide, m.p. 246°-247° (dec.).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Reaction of a mixture of 4-chloro-5-sulfamoylphthalimide (6.48 g., 0.025 mole) and 4-amino-1-(4-bromobenzyl)piperidine (6.7 g., 0.025 mole) in n-pentanol according to the procedure of Example 1(a) afforded the 1,3-dioxoisoindole product. Purification of the crude product by triturating with n-heptane and crystallization from DMF-methanol afforded 6.9 g. (54%) of 2-[1-[(4-bromophenyl)methyl]-4-piperidinyl]-6-chloro-2,3-dihydro-1,3-dioxo-1H-isoindole-5-sulfonamide, m.p. 246°-247° (dec.).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo benzylbromide (1.0 g, 4.1 mmol) in dichloromethane (20 ml) and diisopropyletylamine (1 ml) was added tert-butyl 4-piperidinylcarbamate (1.0 g, 5.0 mmol). The solution was then stirred at room temperature over night. The solvent was evaporated and 25 ml of 50% TFA in dichloromethane was added to the resulting white solid. The mixture was then stirred at room temperature for 2 h and then evaporated to dryness. The resulting solid was dissolved in water and extracted with toluene. After removal of the toluene the water phase was made basic with 1M NaOH giving a pH of 13. The water phase was then extracted with dichloromethane 3 times and the combined extracts were dried and then evaporated to give the pure product as a slightly yellow oil (0.96 g, 3.6 mmol) The solvent was evaporated 25 ml of 50% TFA in dichloromethane was added to the resulting white solid The mixture was then stirred at room temperature for 2 h evaporated to dryness The resulting solid was dissolved in water extracted with toluene After removal of the toluene the water phase The water phase was then extracted with dichloromethane 3 times the combined extracts were dried evaporated