1-acetylpyrrolidin-2-one

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

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

Procedure: A mixture of 112 g of 2-pyrrolidinone (9) and 249 mL of acetic anhydride was heated at reflux for 2 hours. The resultant mixture was allowed to cool to room temperature, was concentrated in vacuo, and was distilled (0.8 mm Hg, 68° C.) to provide 160 g of N-acetyl-2-pyrrolidinone (4) in 96% yield. was heated at reflux for 2 hours was concentrated in vacuo was distilled (0.8 mm Hg, 68° C.)

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

Procedure: A mixture of 112 g of 2-pyrrolidinone (9) and 249 mL of acetic anhydride was heated at reflux for 2 hours. The resultant mixture was allowed to cool to room temperature, was concentrated in vacuo, and was distilled (0.8 mm Hg, 68° C.) to provide 160 g of N-acetyl-2-pyrrolidinone (4) in 96% yield. was heated at reflux for 2 hours was concentrated in vacuo was distilled (0.8 mm Hg, 68° C.)

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

Procedure: Sodium hydride (16 g) was suspended in tetrahydrofuran (100 ml) and a solution of N-acetylpyrrolidone (25 g) and o-anisaldehyde (26.8 g) in tetrahydrofuran (100 ml) was added dropwise under ice-cooling. After completion of the reaction, the reaction mixture was poured into water. The mixture was acidified with hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to give oily 3-(2′-methoxybenzylidene)-2-pyrrolidone (4.7 g). The oil was dissolved in methylene chloride (60 ml). By demethylation using boron tribromide under ice-cooling, 3-(2′-hydroxybenzylidene)-2-pyrrolidone (4.0 g) was obtained as yellow crystals. To the crystals (1.5 g) were added dimethylformamide (50 ml) and potassium carbonate (2.2 g). (S)-Glycidyl nosylate (2.3 g) was added and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure and water was added. The mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate to give an oily compound (1.8 g). By the reaction of the oil (0.5 g) and 4-(5,6,7,8-tetrahydronaphthalen-2-yl)piperidine (0.5 g) in methanol in the same manner as in Example 307, the title compound (0.4 g) was obtained, melting point 157–159° C. cooling After completion of the reaction extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate After filtration the solvent was evaporated under reduced pressure

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

Procedure: Sodium hydride (16 g) was suspended in tetrahydrofuran (100 ml) and a solution of N-acetylpyrrolidone (25 g) and o-anisaldehyde (26.8 g) in tetrahydrofuran (100 ml) was added dropwise under ice-cooling. After completion of the reaction, the reaction mixture was poured into water. The mixture was acidified with hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to give oily 3-(2′-methoxybenzylidene)-2-pyrrolidone (4.7 g). The oil was dissolved in methylene chloride (60 ml). By demethylation using boron tribromide under ice-cooling, 3-(2′-hydroxybenzylidene)-2-pyrrolidone (4.0 g) was obtained as yellow crystals. To the crystals (1.5 g) were added dimethylformamide (50 ml) and potassium carbonate (2.2 g). (S)-Glycidyl nosylate (2.3 g) was added and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure and water was added. The mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate to give an oily compound (1.8 g). By the reaction of the oil (0.5 g) and 4-(5,6,7,8-tetrahydronaphthalen-2-yl)piperidine (0.5 g) in methanol in the same manner as in Example 307, the title compound (0.4 g) was obtained, melting point 157–159° C. cooling After completion of the reaction extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate After filtration the solvent was evaporated under reduced pressure

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

Procedure: A solution of 5.0 g of N-acetyl-2-pyrrolidone and 5.17 g of 4-cyanobenzaldehyde in 50 ml of tetrahydrofuran is added dropwise to a suspension of 5.36 g of sodium hydride (55% in oil) in 50 ml of tetrahydrofuran at 5°-10° C. and the mixture is then stirred at 0° C. for 1 hour. Excess sodium hydride is eliminated by the addition of some methanol, and the reaction mixture is poured onto ice and neutralized with glacial acetic acid. The precipitate is suction-filtered and dissolved in a methylene chloride/methanol mixture, and the solution is dried and evaporated down. The residue is triturated with ether and suction-filtered. 1.4 g of 3-(4-cyanobenzylidene)-2-pyrrolidone are obtained as a colourless powder of melting point 260° C. The precipitate is suction-filtered dissolved in a methylene chloride/methanol mixture the solution is dried evaporated down The residue is triturated with ether suction-filtered

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

Procedure: A solution of 5.0 g of N-acetyl-2-pyrrolidone and 5.17 g of 4-cyanobenzaldehyde in 50 ml of tetrahydrofuran is added dropwise to a suspension of 5.36 g of sodium hydride (55% in oil) in 50 ml of tetrahydrofuran at 5°-10° C. and the mixture is then stirred at 0° C. for 1 hour. Excess sodium hydride is eliminated by the addition of some methanol, and the reaction mixture is poured onto ice and neutralized with glacial acetic acid. The precipitate is suction-filtered and dissolved in a methylene chloride/methanol mixture, and the solution is dried and evaporated down. The residue is triturated with ether and suction-filtered. 1.4 g of 3-(4-cyanobenzylidene)-2-pyrrolidone are obtained as a colourless powder of melting point 260° C. The precipitate is suction-filtered dissolved in a methylene chloride/methanol mixture the solution is dried evaporated down The residue is triturated with ether suction-filtered

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

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

Procedure: Sodium hydride (16 g) was suspended in tetrahydrofuran (100 ml) and a solution of N-acetylpyrrolidone (25 g) and o -anisaldehyde (26.8 g) in tetrahydrofuran (100 ml) was added dropwise under ice-cooling. After completion of the reaction, the reaction mixture was poured into water. The mixture was acidified with hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to give oily 3-(2′-methoxybenzylidene)-2-pyrrolidone (4.7 g). The oil was dissolved in methylene chloride (60 ml). By demethylation using boron tribromide under ice-cooling, 3-(2′-hydroxybenzylidene)-2-pyrrolidone (4.0 g) was obtained as yellow crystals. To the crystals (1.5 g) were added dimethylformamide (50 ml) and potassium carbonate (2.2 g). (S)-Glycidyl nosylate (2.3 g) was added and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure and water was added. The mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate to give an oily compound (1.8 g). By the reaction of the oil (0.5 g) and 4-(5,6,7,8-tetrahydronaphthalen-2-yl)piperidine (0.5 g) in methanol in the same manner as in Example 307, the title compound (0.4 g) was obtained, melting point 157-159° C. cooling After completion of the reaction extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate After filtration the solvent was evaporated under reduced pressure

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

Procedure: The title compound was prepared via reaction between 2-pyridin-4-yl-benzaldehyde and N-acetylpyrrolidinone using General Aldol Procedure 1. 13C NMR (100 MHz, CDCl3) d 172.6, 149.9, 148.5, 140.0, 133.7, 132.8, 130.3, 128.9, 128.7, 128.4, 124.8, 40.0, 26.4; MS (AP/Cl) 252.1 (M+H)+.

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

Procedure: A solution of 9.0 g (40.5 mmol) of 5-Fluoro-2-(4-methyl-piperazin-1-yl)-benzaldehyde and 5.1 g (40.5 mmol) of N-acetylpyrrolidinone in 80 mL of tetrahydrofuran is slowly added to a 0° C. solution of 5.4 g (133.6 mmol) of sodium hydride in 80 mL of tetrahydrofuran over a 2 hour period. After 2.5 hour at 0° C., the reaction is quenched with sat. ammonium chloride and extracted with methylene chloride. The organic layer is dried with magnesium sulfate and concentrated to provide a yellow solid. Recrystallization from ethyl acetate and diispropyl ether provided 3.92 g (33%) of 3-[5-Fluoro-2-(4-methyl-piperazin-1-yl)-benzylidene]-pyrrolidin-2-one as a white solid. Diagnostic C13 NMR (100 MHz, CDCl3) 26.4, 39.9, 46.1, 52.9, 55.3, 115.2, 115.5, 115.8, 116.0, 120.2, 120.3, 126.7, 131.1, 148.9, 157.3, 159.7, 172.8; MS m/z 290.3 (M+1). the reaction is quenched with sat. ammonium chloride extracted with methylene chloride The organic layer is dried with magnesium sulfate concentrated to provide a yellow solid Recrystallization from ethyl acetate and diispropyl ether

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

Procedure: A mixture of 112 g of 2-pyrrolidinone (9) and 249 mL of acetic anhydride was heated at reflux for 2 hours. The resultant mixture was allowed to cool to room temperature, was concentrated in vacuo, and was distilled (0.8 mm Hg, 68° C.) to provide 160 g of N-acetyl-2-pyrrolidinone (4) in 96% yield. was heated at reflux for 2 hours was concentrated in vacuo was distilled (0.8 mm Hg, 68° C.)