N-(1-azabicyclo[2.2.2]octan-3-yl)-3-chlorobenzamide

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

Procedure: N-(3-Quinuclidinyl)-3-chlorobenzamide (52.5 g) dissolved in methanol is added to a solution of D-tartaric acid (29.7 g) in methanol. The precipitate obtained is collected by filtration and treated twice with methanol under reflux. The salt thus purified (20 g) is decomposed with aqueous sodium hydroxide solution and the product extracted with chloroform. After the organic phase has been dried and evaporated, the base obtained is treated in acetone with ethanolic hydrogen chloride solution. The hydrochloride which precipitates is collected by filtration and recrystallized in ethanol. 9.4 g of optically pure (S)-(-)-N-(3-quinuclidinyl)-3-chlorobenzamide hydrochloride are obtained. The precipitate obtained is collected by filtration treated twice with methanol under reflux The salt thus purified (20 g) the product extracted with chloroform After the organic phase has been dried evaporated the base obtained The hydrochloride which precipitates is collected by filtration recrystallized in ethanol

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

Procedure: N-(3-Quinuclidinyl)-3-chlorobenzamide (52.5 g) dissolved in methanol is added to a solution of D-tartaric acid (29.7 g) in methanol. The precipitate obtained is collected by filtration and treated twice with methanol under reflux. The salt thus purified (20 g) is decomposed with aqueous sodium hydroxide solution and the product extracted with chloroform. After the organic phase has been dried and evaporated, the base obtained is treated in acetone with ethanolic hydrogen chloride solution. The hydrochloride which precipitates is collected by filtration and recrystallized in ethanol. 9.4 g of optically pure (S)-(-)-N-(3-quinuclidinyl)-3-chlorobenzamide hydrochloride are obtained. The precipitate obtained is collected by filtration treated twice with methanol under reflux The salt thus purified (20 g) the product extracted with chloroform After the organic phase has been dried evaporated the base obtained The hydrochloride which precipitates is collected by filtration recrystallized in ethanol

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

Procedure: N-(3-Quinuclidinyl)-3-chlorobenzamide (52.5 g) dissolved in methanol is added to a solution of D-tartaric acid (29.7 g) in methanol. The precipitate obtained is collected by filtration and treated twice with methanol under reflux. The salt thus purified (20 g) is decomposed with aqueous sodium hydroxide solution and the product extracted with chloroform. After the organic phase has been dried and evaporated, the base obtained is treated in acetone with ethanolic hydrogen chloride solution. The hydrochloride which precipitates is collected by filtration and recrystallized in ethanol. 9.4 g of optically pure (S)-(-)-N-(3-quinuclidinyl)-3-chlorobenzamide hydrochloride are obtained. The precipitate obtained is collected by filtration treated twice with methanol under reflux The salt thus purified (20 g) the product extracted with chloroform After the organic phase has been dried evaporated the base obtained The hydrochloride which precipitates is collected by filtration recrystallized in ethanol

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

Procedure: In 60 ml of methanol was dissolved 23 g of N-(3-quinuclidinyl)-3-chlorobenzamide followed by addition of a solution of D-(-)-tartaric acid (13 g) in 40 ml of methanol. The mixture was ice-cooled and the resulting crystals were recovered by filtration. To the crystals was added 350 ml of methanol and the mixture was refluxed for a while. After cooling, the crystals were collected by filtration. The above operation was repeated twice and the crystals obtained were dissolved in water and sodium hydroxide solution was added. This mixture was extracted with chloroform and the extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was then evaporated off to obtain a colorless oil. This oil was treated with ethanolic hydrochloric acid in acetone and the precipitated hydrochloride was recovered by filtration to give 11.4 g of the desired compound as white crystals. m.p. 244°-246° C. cooled the resulting crystals were recovered by filtration To the crystals was added 350 ml of methanol the mixture was refluxed for a while After cooling the crystals were collected by filtration the crystals obtained This mixture was extracted with chloroform the extract was washed with water dried over anhydrous magnesium sulfate The solvent was then evaporated off to obtain a colorless oil the precipitated hydrochloride was recovered by filtration

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

Procedure: In 400 ml of acetonitrile was suspended 25 g of m-chlorobenzoic acid and while the suspension was stirred with ice-cooling, 39.5 g of N,N'-dicyclohexylcarbodiimide and 27.0 g of 1-hydroxybenzotriazole monohydrate were added. The mixture was stirred for 2 hours. Then, 20.2 g of 3-aminoquinuclidine was added and the mixture was further stirred with ice-cooling for 2 hours and, then, at room temperature for 20 hours. The reaction mixture was filtered to remove insolubles and the solvent was evaporated off. The residue was dissolved by addition of diluted hydrochloric acid and washed twice with ethyl acetate. The aqueous layer was neutralized with aqueous solution of sodium hydroxide and extracted with chloroform. The extract was washed with water and dried over anhydrous magnesium sulfate and the chloroform was evaporated off to give 42.1 g of the desired compound as white crystals. cooling The mixture was stirred for 2 hours the mixture was further stirred with ice- cooling for 2 hours The reaction mixture was filtered to remove insolubles the solvent was evaporated off The residue was dissolved by addition of diluted hydrochloric acid washed twice with ethyl acetate extracted with chloroform The extract was washed with water dried over anhydrous magnesium sulfate the chloroform was evaporated off