2-(2-chloroethoxy)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:

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: 15.13 g of (2-chloroethoxy)acetamide (0.11 mol), 14.6 ml of ethyl piperazine carboxylate (0.1 mol), 23.3 g of sodium carbonate (0.22 mol) and 1.0 g of potassium iodide in 25 ml of toluene are introduced into a round-bottomed flask fitted with a water-cooled condenser and a mechanical stirrer. The mixture is heated at the reflux temperature for 4 hours and is allowed to cool to room temperature. The reaction is continued, still with stirring, for a further 16 hours. 100 ml of isopropanol are added and the solid materials formed are filtered off. The solvent is evaporated from the filtrate under reduced pressure to dryness. The product obtained after evaporation of the solvents is recrystallized from toluene. 21.35 g of ethyl 4-(2-carbamoylmethoxyethyl)piperazine-1-carboxylate are obtained. cooled condenser and a mechanical stirrer The mixture is heated at the reflux temperature for 4 hours the solid materials formed are filtered off The solvent is evaporated from the filtrate under reduced pressure to dryness The product obtained after evaporation of the solvents is recrystallized from toluene

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 164 g (1.04 mol) of ethyl piperazinecarboxylate, 156.9 g (1.14 mol) of (2-chloroethoxy)acetamide, 241.7 g (2.28 mol) of sodium carbonate, 1 g of potassium iodide and 200 ml of toluene are introduced into a 2 1 three-necked round-bottomed flask fitted with a water-cooled condenser and a mechanical stirrer. The mixture is brought at the reflux temperature for 3 hours 30. The mixture is allowed to cool to 50° C., and 200 ml of isopropanol are added. The reaction mixture is filtered and the filtration residue is washed with 150 ml of isopropanol. The filtrate is concentrated on a rotary evaporator under reduced pressure. 272.2 g of crude product are obtained, which product is recrystallized from 500 ml of ethyl acetate. 219.2 g (81.6%) of ethyl (2-carbamoylmethoxyethyl)piperazine-1-carboxylate are obtained in the form of a white solid. cooled condenser and a mechanical stirrer The reaction mixture is filtered the filtration residue is washed with 150 ml of isopropanol The filtrate is concentrated on a rotary evaporator under reduced pressure 272.2 g of crude product are obtained which product is recrystallized from 500 ml of ethyl acetate

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

実験手順: A mixture of 13.15 g of (2-chloroethoxy)acetamide (0.1 mol) and 43 g of anhydrous piperazine (0.5 mol) in 250 ml of toluene is introduced into a round-bottomed flask fitted with a water-cooled condenser and a mechanical stirrer. The mixture is heated at the reflux temperature for 4 hours. The precipitate formed is filtered off while hot and the solvent of the filtrate is evaporated off under reduced pressure to dryness. The evaporation residue is purified by chromatography on silica gel (eluent: 14/5/1 (v/v/v) of dichloromethane/methanol/28% aqueous ammonia solution). 7.4 g of 2-[2-(1-piperazinyl)ethoxy]acetamide are obtained in the form of a yellow oil is introduced into a round-bottomed flask cooled condenser and a mechanical stirrer The mixture is heated at the reflux temperature for 4 hours The precipitate formed is filtered off while hot and the solvent of the filtrate is evaporated off under reduced pressure to dryness The evaporation residue is purified by chromatography on silica gel (eluent: 14/5/1 (v/v/v) of dichloromethane/methanol/28% aqueous ammonia solution)

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

実験手順: 15 g (0.0523 mole) of dextrorotatory (+)-1-[(4-chlorophenyl)phenylmethyl]piperazine (prepared in Example 4.2), 8.3 g (0.0601 mole) of 2-(2-chloroethoxy)acetamide, 12.8 g (0.1203 mole) of sodium carbonate and 0.5 g (0.0030 mole) of potassium iodide are added to a mixture of 100 ml of p-xylene and 150 ml of toluene. The mixture is heated at reflux temperature for 17 hours. A small amount of Norit is added and the mixture is filtered while hot through Dicalite. The residue on the filter is washed with a small amount of toluene and the filtrate and washing solution are combined. The solvents are evaporated and the residue is taken up in 100 ml of toluene. The organic phase is washed successively with 100 ml of water and twice with 100 ml of a saturated aqueous solution of sodium chloride. The organic phase is separated off and the solvent evaporated. At this point, the crude residue obtained could be purified in a manner similar to that described at point 9 above, in order to obtain dextrorotatory (+)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide in the form of the free base. However, if desired, the crude residue may also be converted to the corresponding dihydrochloride in the following manner: the crude residue obtained is taken up in 100 ml of acetone, cooled in an ice bath and 15 ml of concentrated hydrochloric acid are added dropwise thereto. A further 200 ml of acetone are added and the mixture is cooled and stirred on an ice bath for 1 hour. The precipitate is filtered off and dried under vacuum at 50° C. 19 g of the levorotatory dihydrochloride of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide are obtained. The mixture is heated at reflux temperature for 17 hours the mixture is filtered while hot through Dicalite The residue on the filter is washed with a small amount of toluene the filtrate and washing solution The solvents are evaporated The organic phase is washed successively with 100 ml of water and twice with 100 ml of a saturated aqueous solution of sodium chloride The organic phase is separated off the solvent evaporated At this point, the crude residue obtained could be purified in a manner similar to

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

実験手順: 15 g (0.0523 mole) of dextrorotatory (+)-1-[(4-chlorophenyl)phenylmethyl]piperazine (prepared in Example 4.2), 8.3 g (0.0601 mole) of 2-(2-chloroethoxy)acetamide, 12.8 g (0.1203 mole) of sodium carbonate and 0.5 g (0.0030 mole) of potassium iodide are added to a mixture of 100 ml of p-xylene and 150 ml of toluene. The mixture is heated at reflux temperature for 17 hours. A small amount of Norit is added and the mixture is filtered while hot through Dicalite. The residue on the filter is washed with a small amount of toluene and the filtrate and washing solution are combined. The solvents are evaporated and the residue is taken up in 100 ml of toluene. The organic phase is washed successively with 100 ml of water and twice with 100 ml of a saturated aqueous solution of sodium chloride. The organic phase is separated off and the solvent evaporated. At this point, the crude residue obtained could be purified in a manner similar to that described at point 9 above, in order to obtain dextrorotatory (+)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide in the form of the free base. However, if desired, the crude residue may also be converted to the corresponding dihydrochloride in the following manner: the crude residue obtained is taken up in 100 ml of acetone, cooled in an ice bath and 15 ml of concentrated hydrochloric acid are added dropwise thereto. A further 200 ml of acetone are added and the mixture is cooled and stirred on an ice bath for 1 hour. The precipitate is filtered off and dried under vacuum at 50° C. 19 g of the levorotatory dihydrochloride of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide are obtained. The mixture is heated at reflux temperature for 17 hours the mixture is filtered while hot through Dicalite The residue on the filter is washed with a small amount of toluene the filtrate and washing solution The solvents are evaporated The organic phase is washed successively with 100 ml of water and twice with 100 ml of a saturated aqueous solution of sodium chloride The organic phase is separated off the solvent evaporated At this point, the crude residue obtained could be purified in a manner similar to

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

実験手順: 77 g (0.2685 mole) of levorotatory (-)-1-[(4-chlorophenyl)phenylmethyl]piperazine (prepared in Example 4.1), 40.5 g (0.2932 mole) of 2-(2-chloroethoxy)acetamide, 62.8 g (0.591 mole) of sodium carbonate and 2 g (0.0120 mole) of potassium iodide are added to 700 ml of toluene. The mixture is heated at reflux temperature for 24 hours. 10 g of Norit are then added and the mixture is filtered while hot through Dicalite. The filtrate is washed with 500 ml of water and then with 500 ml of a saturated aqueous solution of sodium chloride. The organic phase is separated and dried over 250 g of sodium sulfate. It is then filtered and the solvent is evaporated. The residual oil is taken up in 1500 ml of hot diisopropyl oxide. The solution is heated under reflux and allowed to crystallize by cooling in an ice bath. The crystals are filtered, washed with a small amount of diisopropyl oxide and dried under vacuum at 40° C. 82.91 g of levorotatory (-)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide are obtained. The mixture is heated at reflux temperature for 24 hours the mixture is filtered while hot through Dicalite The filtrate is washed with 500 ml of water The organic phase is separated dried over 250 g of sodium sulfate It is then filtered the solvent is evaporated The solution is heated under reflux to crystallize by cooling in an ice bath The crystals are filtered washed with a small amount of diisopropyl oxide dried under vacuum at 40° C

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

実験手順: 15.13 g of (2-chloroethoxy)acetamide (0.11 mol), 14.6 ml of ethyl piperazine carboxylate (0.1 mol), 23.3 g of sodium carbonate (0.22 mol) and 1.0 g of potassium iodide in 25 ml of toluene are introduced into a round-bottomed flask fitted with a water-cooled condenser and a mechanical stirrer. The mixture is heated at the reflux temperature for 4 hours and is allowed to cool to room temperature. The reaction is continued, still with stirring, for a further 16 hours. 100 ml of isopropanol are added and the solid materials formed are filtered off. The solvent is evaporated from the filtrate under reduced pressure to dryness. The product obtained after evaporation of the solvents is recrystallized from toluene. 21.35 g of ethyl 4-(2-carbamoylmethoxyethyl)piperazine-1-carboxylate are obtained. cooled condenser and a mechanical stirrer The mixture is heated at the reflux temperature for 4 hours the solid materials formed are filtered off The solvent is evaporated from the filtrate under reduced pressure to dryness The product obtained after evaporation of the solvents is recrystallized from toluene

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 164 g (1.04 mol) of ethyl piperazinecarboxylate, 156.9 g (1.14 mol) of (2-chloroethoxy)acetamide, 241.7 g (2.28 mol) of sodium carbonate, 1 g of potassium iodide and 200 ml of toluene are introduced into a 2 1 three-necked round-bottomed flask fitted with a water-cooled condenser and a mechanical stirrer. The mixture is brought at the reflux temperature for 3 hours 30. The mixture is allowed to cool to 50° C., and 200 ml of isopropanol are added. The reaction mixture is filtered and the filtration residue is washed with 150 ml of isopropanol. The filtrate is concentrated on a rotary evaporator under reduced pressure. 272.2 g of crude product are obtained, which product is recrystallized from 500 ml of ethyl acetate. 219.2 g (81.6%) of ethyl (2-carbamoylmethoxyethyl)piperazine-1-carboxylate are obtained in the form of a white solid. cooled condenser and a mechanical stirrer The reaction mixture is filtered the filtration residue is washed with 150 ml of isopropanol The filtrate is concentrated on a rotary evaporator under reduced pressure 272.2 g of crude product are obtained which product is recrystallized from 500 ml of ethyl acetate