3-Phenylpiperazin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred solution of triphosgene (0.558 g) in DCM (10 ml) pyridine (0.46 mL) was added at 0° C. and, after 10 min, 3-phenyl-piperazine-2-one (1 g). The ice bath was removed and the mixture was stirred at room temperature overnight. The mixture was concentrated and the product was purified by flash chromatography (CH/AcOEt 1:1) to give the title compound (0.253 g) as a foam. The ice bath was removed The mixture was concentrated the product was purified by flash chromatography (CH/AcOEt 1:1)

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

Procedure: To a stirred solution of triphosgene (0.558 g) in DCM (10 ml) pyridine (0.46 mL) was added at 0° C. and, after 10 min, 3-phenyl-piperazine-2-one (1 g). The ice bath was removed and the mixture was stirred at room temperature overnight. The mixture was concentrated and the product was purified by flash chromatography (CH/AcOEt 1:1) to give the title compound (0.253 g) as a foam. The ice bath was removed The mixture was concentrated the product was purified by flash chromatography (CH/AcOEt 1:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To an ice-cooled stirred suspension of 25. g (0.66 mol) of lithium aluminum hydride in 2.6 liters of anhydrous ether was added in portions over 0.5 hour 30 g (0.17 mol) of 3-phenyl-2-piperazinone. The resulting mixture was heated at reflux for 20 hours and then cooled to 0° C. Isolation of the product by standard methods gave 23 g (83%) of 2-phenylpiperazine as an off-white solid (mp. 83°-85° C.). The resulting mixture was heated at reflux for 20 hours

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

Procedure: A stirred mixture of 58.0 g (0.33 mol) of 3-phenyl-2-piperazinone, 85 g (0.62 mol) of blended potassium carbonate, and 76.9 g (0.33 mol) of 4-chlorophenacyl bromide in 400 ml of dichloromethane was heated at reflux for 12 hours. The mixture was cooled to ambient temperature, filtered, and the solid washed thoroughly with dichloromethane. The filtrate was concentrated to dryness, isopropanol added and stirred, the solid collected by filtration, washed thoroughly with isopropanol and dried in a vacuum oven at 50° C. to give 92.5 g (85 %) of 3-phenyl-4-(4-chlorophenacyl)-2-piperazinone. This material was used in Example 2 of the process. Pure material could be obtained by recrystallization from methanol to give a white solid (mp. 157°-158° C. dec.). was heated at reflux for 12 hours filtered the solid washed thoroughly with dichloromethane The filtrate was concentrated to dryness, isopropanol added the solid collected by filtration washed thoroughly with isopropanol dried in a vacuum oven at 50° C.

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

Procedure: To a stirred solution of 1928 g (32.1 mol) of ethylenediamine in 2 liters of absolute ethanol was added a solution of 3130 g (12.8 mol) of ethyl α-bromophenylacetate in 4 liters of absolute ethanol at such a rate so as to maintain reflux (~45 minutes addition time). The mixture was allowed to cool to ambient temperature and then concentrated to a thick yellow slurry. The slurry was stirred with 2 liters of chloroform, filtered, and the solid washed thoroughly with chloroform (total of 8 liters). The filtrate was concentrated to near dryness and the resulting residue stirred for a short time with 2 liters of isopropanol. The solid was collected by filtration, washed with 4 liters of isopropanol, and dried to give 1224 g (54%) of 3-phenyl-2-piperazinone. This material was used as such in the next step. [Pure material could be obtained by recrystallization from benzene and then from acetone to give a white solid (mp. 139.0°-139.5° C. ).] to maintain reflux (~45 minutes addition time) concentrated to a thick yellow slurry filtered the solid washed thoroughly with chloroform (total of 8 liters) The filtrate was concentrated the resulting residue stirred for a short time with 2 liters of isopropanol The solid was collected by filtration washed with 4 liters of isopropanol dried

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

Procedure: To a stirred solution of 1928 g (32.1 mol) of ethylenediamine in 2 liters of absolute ethanol was added a solution of 3130 g (12.8 mol) of ethyl α-bromophenylacetate in 4 liters of absolute ethanol at such a rate so as to maintain reflux (~45 minutes addition time). The mixture was allowed to cool to ambient temperature and then concentrated to a thick yellow slurry. The slurry was stirred with 2 liters of chloroform, filtered, and the solid washed thoroughly with chloroform (total of 8 liters). The filtrate was concentrated to near dryness and the resulting residue stirred for a short time with 2 liters of isopropanol. The solid was collected by filtration, washed with 4 liters of isopropanol, and dried to give 1224 g (54%) of 3-phenyl-2-piperazinone. This material was used as such in the next step. [Pure material could be obtained by recrystallization from benzene and then from acetone to give a white solid (mp. 139.0°-139.5° C. ).] to maintain reflux (~45 minutes addition time) concentrated to a thick yellow slurry filtered the solid washed thoroughly with chloroform (total of 8 liters) The filtrate was concentrated the resulting residue stirred for a short time with 2 liters of isopropanol The solid was collected by filtration washed with 4 liters of isopropanol dried

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

Procedure: 144 g. of 2-phenyl-3-keto piperazine are boiled under reflux with 121 g. of diethylamino ethylchloride, 340 cc. of triethylamine, and 1600 cc. of acetone for 24 hours. The cooled solution is filtered to remove triethylamine hydrochloride and the filtrate is evaporated to dryness. The residue is dissolved in water, 40 % sodium hydroxide solution is added thereto, and the oil which forms as upper layer, is extracted with benzene. The benzene solution is dried over anhydrous potassium carbonate, the benzene is removed by distillation, and the residue is distilled in a vacuum. A light yellow, viscous oil of the boiling point 175° C./0.05 mm. Hg is obtained. The oil is twice recrystallized from n-heptane. 145 g. of the above mentioned compound melting at 53°-56° C. are obtained. The yield is 64 % of the theoretical yield. under reflux with 121 g The cooled solution is filtered to remove triethylamine hydrochloride the filtrate is evaporated to dryness The residue is dissolved in water 40 % sodium hydroxide solution is added is extracted with benzene The benzene solution is dried over anhydrous potassium carbonate the benzene is removed by distillation the residue is distilled in a vacuum A light yellow, viscous oil of the boiling point 175° C./0.05 mm. Hg is obtained The oil is twice recrystallized from n-heptane are obtained

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

Procedure: 140 g. of 2-phenyl-3-keto piperazine are boiled under reflux with 163 g. of 3,4-dichloro benzylchloride in 1,600 cc. of acetone for 6 hours while 330 cc. of triethylamine are added. The hot reaction mixture is filtered to remove precipitated triethyl ammonium chloride and is concentrated by fractional distillation. The resulting crystal fractions are twice recrystallized from 4 l. of 96% ethanol. under reflux with 163 g The hot reaction mixture is filtered to remove precipitated triethyl ammonium chloride is concentrated by fractional distillation The resulting crystal fractions are twice recrystallized from 4 l

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

Procedure: To a stirred solution of triphosgene (0.558 g) in DCM (10 ml) pyridine (0.46 mL) was added at 0° C. and, after 10 min, 3-phenyl-piperazine-2-one (1 g). The ice bath was removed and the mixture was stirred at room temperature overnight. The mixture was concentrated and the product was purified by flash chromatography (CH/AcOEt 1:1) to give the title compound (0.253 g) as a foam. The ice bath was removed The mixture was concentrated the product was purified by flash chromatography (CH/AcOEt 1:1)