1-(2-methylpropyl)piperazine;dihydrochloride

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

Procedure: To 1-isobutylpiperazine dihydrochloride(69.5 g) was added 10% aqueous solution of sodium hydrochloride(100 ml) and the mixture was extracted with ether. After being concentrated, the extract was distilled under a vacuum(bp 172°-174° C./5 mmHg), thereby yielding 43.7 g of 1-isobutylpiperazine. the mixture was extracted with ether After being concentrated the extract was distilled under a vacuum(bp 172°-174° C./5 mmHg)

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

Procedure: As in the case of Example 22 which will be explained later, 1-[4-(4-fluorobenzyloxy)benzoyl]-4-isobutylpiperazine (compound of Example 5) (1.52 g) was converted into the corresponding hydrochloride salt, thereby yielding 1.65 g of the aimed compound.

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

Procedure: To 1-isobutylpiperazine dihydrochloride (69.5 g) was added 10% aqueous sodium hydroxide solution (100 ml) and then the resulting mixture was extracted with ether. After the extract was concentrated, the residue was distilled under reduced pressure (bp: 172° to 174° C./5 mmHg), thereby yielding 43.7 g of the aimed compound. the resulting mixture was extracted with ether After the extract was concentrated the residue was distilled under reduced pressure (bp: 172° to 174° C./5 mmHg)

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

Procedure: A mixture of 125 ml of nitromethane, 35 ml of toluene, 20 ml of ethanol, and 1 ml of concentrated hydrochloric acid was mixed together with 18.6 g of 4'-methylpropiophenone, 27.0 g of N-isobutylpiperazine dihydrochloride and 8.5 g of trioxane. The mixture was heated with stirring under reflux for 4 hrs. while distilling off water generated through the reaction. After cooling, the reaction mixture was added with ether, and the precipitate was filtered, which was dissolved in water. The solution was adjusted to pH 6 with 5N sodium hydroxide, washed with ether, and further adjusted to pH 7 with 5N sodium hydroxide. The obtained solution was extracted with ether and the extract was dried, and white crystals generated by introducing dry hydrogen chloride were filtered and dried. The product was recrystallized from an ethanol-acetone mixed solvent, yielding 2,4'-dimethyl-3-(4-isobutylpiperazino)propiophenone dihydrochloride. (yield 46.5%), m.p. 215°-220° C. The mixture was heated under reflux for 4 hrs while distilling off water generated through the reaction After cooling the precipitate was filtered which was dissolved in water washed with ether The obtained solution was extracted with ether the extract was dried by introducing dry hydrogen chloride were filtered dried The product was recrystallized from an ethanol-acetone mixed solvent

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

Procedure: A mixture of 125 ml of nitromethane, 35 ml of toluene, 20 ml of ethanol, and 1 ml of concentrated hydrochloric acid was mixed together with 18.6 g of 4'-methylpropiophenone, 27.0 g of N-isobutylpiperazine dihydrochloride and 8.5 g of trioxane. The mixture was heated with stirring under reflux for 4 hrs. while distilling off water generated through the reaction. After cooling, the reaction mixture was added with ether, and the precipitate was filtered, which was dissolved in water. The solution was adjusted to pH 6 with 5 N sodium hydroxide, washed with ether, and furtheradjusted to pH 7 with 5 N sodium hydroxide. The obtained solution was extracted with ether and the extract was dried, and white crystals generated by introducing dry hydrogen chloride were filtered and dried. The product was recrystallized from an ethanol-acetone mixed solvent, yielding 2,4'-dimethyl-3-(4-isobutylpiperazino)propiophenone dihydrochloride. (yield 46.5%), m.p. 215°-220° C. The mixture was heated under reflux for 4 hrs while distilling off water generated through the reaction After cooling the precipitate was filtered which was dissolved in water washed with ether The obtained solution was extracted with ether the extract was dried by introducing dry hydrogen chloride were filtered dried The product was recrystallized from an ethanol-acetone mixed solvent