1-(4-methoxybenzoyl)pyrrolidin-2-one [Aniracetam] by Asch

Reaxys

PubChem

eMolecules

Reactions (14)

Yield

Substances (3)

Page 1 of 1

Citations (6)

Conditions

References

Synthesize Find similar

Rx-ID: 38733156 Find similar reactions

Stage #1: 4-methoxy-benzoic acid With thionyl chloride

T=76°C; 3 h; Stage #2: pyrrolidin-2-one With triethylamine in toluene

T=50 - 110°C; 2.5 h; Hide Experimental Procedure

Synthesize Find similar

Zaklady Farmaceutyczne Polpharma SA; Szramka, Roman; Sagol, Karol; Poojari, Krishna

Patent: EP2604592 B1, 2014 ; Location in patent: Paragraph 0018 ; Title/Abstract Full Text Show Details

1:A process for the preparation of crude aniracetam.

94 g (0.79 mol) of thionyl chloride and 30 g (0.197) of 4-methoxybenzoic acid was measured into a 250 mL round-bottom flask fitted with a stirrer, thermometer and reflux condenser. Subsequently, the mixture was heated to a boil (76°C) and maintained at that temperature for three hours upon stirring; subsequently, the unreacted thionyl chloride was distilled off in vacuum. The distillation residue was cooled to 50°C and dissolved in 120 mL of toluene. 26.0 g (0.256 mol) of triethylamine and 17.6 g (0.207 mol) of 2-pyrrolidone was added to the toluene solution. The reaction mixture was heated to a boil (110°C) and maintained under reflux for 2.5 hours; subsequently, it was cooled to 20°C and 60 mL of water was added. The precipitate of crude aniracetam was filtered off, washed three times with 50 mL of water and dried. 34.9 g of a crude product was obtained with a yield of 80percent.

Synthesize Find similar

Rx-ID: 40598236 Find similar reactions

89%

Synthesize Find similar

With bis[2-(diphenylphosphino)phenyl] ether; PdI2 in toluene

T=105°C; P=37503.8 Torr; 20 h; Inert atmosphereAutoclave; regioselective reaction;

Li, Haoquan; Dong, Kaiwu; Neumann, Helfried; Beller, Matthias

Angewandte Chemie - International Edition, 2015 , vol. 54, # 35 p. 10239 - 10243 Angew. Chem., 2015 , vol. 127, # 35 p. 10377 - 10381,5 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 8800509 Find similar reactions

83%

Synthesize Find similar

With triethylamine in tetrahydrofuran

T=0 - 20°C;

Karimi; Kihlberg; Langstroem

Journal of the Chemical Society. Perkin Transactions 1, 2001 , # 13 p. 1528 - 1531 Title/Abstract Full Text View citing articles Show Details

With triethylamine in diethyl ether; water

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

1:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 1 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 40.0 g. of p-methoxybenzoyl chloride, 25.0 g. of 2-pyrrolidinone and 110 ml. of absolute diethyl ether are treated at between 0° C. and 10° C. while stirring with 52.5 ml. of triethylamine. The mixture is stirred at room temperature for a further 30 minutes and at reflux for 3 hours, then cooled down and treated at 2° C. with cold water. The insoluble constituents are filtered off under suction and washed with water and diethyl ether. The thus-obtained solid substance is recrystallized from alcohol after drying over phosphorus pentoxide. There is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone which melts at 121°-122° C.

Hide Experimental Procedure

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ; Title/Abstract Full Text Show Details

5:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 5 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 10 g. of 2-pyrrolidinone and 10 g. of p-methoxybenzoyl chloride are heated at 80°-90° C. (internal temperature) in the absence of a solvent for 1 hour. The mixture is then left to cool down and is worked-up as described in Example 3. After recrystallization from alcohol, there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 120°-121° C.

Hide Details With ammonium hydroxide in diethyl ether

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

3:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 3 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 20 g. of p-methoxybenzoyl chloride and 20 g. of 2-pyrrolidinone are boiled at reflux in 20 ml. of diethyl ether for 16 hours and then diethyl ether, ice and 2-N aqueous ammonia are added to the mixture. The insoluble constituents are filtered off and washed ion-free with diethyl ether and water. The filter cake is dried and there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 119.5°-120.5° C.

Synthesize Find similar

Rx-ID: 25113895 Find similar reactions

Synthesize Find similar

With chloro-trimethyl-silane; sodium hydrogencarbonate; triethylamine; carbon palladium in tetrahydrofuran; ethyl acetate

Hide Experimental Procedure

Synthesize Find similar

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ; Title/Abstract Full Text Show Details

9:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 9 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 10.0 g. of 5-oxo-3-pyrrolidinyl acetate and 8.82 ml. of trimethylchlorosilane are dissolved in 100 ml. of absolute tetrahydrofuran and then 9.65 ml. of triethylamine are added at -5° C. to 0° C. The temperature is held at -5° C. to 0° C. for 1 hour, the mixture is then filtered under an argon atmosphere, the filtrate is evaporated and the residue is distilled in vacuo. There is obtained 5-oxo-1-trimethylsilyl-3-pyrrolidinyl acetate, having a boiling point of 110° C./0.07 mmHg. 12.5 g. of 5-oxo-1-trimethylsilyl-3-pyrrolidinyl acetate are placed in 30 ml. of absolute tetrahydrofuran and then 9.90 g. of p-methoxybenzoyl chloride dissolved in 10 ml. of absolute tetrahydrofuran are added dropwise at 0°-10° C. The mixture is stirred at room temperature for 1 hour and at 70° C. for 1 hour and is then evaporated. The residue is dissolved in ethyl acetate and the ethyl acetate solution is washed with sodium chloride and sodium bicarbonate solution, dried over sodium sulfate and evaporated. 20 ml. of tetrahydrofuran and 20 ml. of saturated sodium bicarbonate solution are added to the residual viscous oil and the mixture obtained is then stirred at room temperature for 18 hours. The solvent mixture is decanted off and the residue is partitioned between water and methylene chloride. The organic phase is separated, dried over sodium sulfate and evaporated. The residual brown oil is chromatographed over silica gel (particle size 0.2-0.5 mm). The 1-(p-methoxybenzoyl)pyrrolin-2-one, which is eluted with benzene/diethyl ether (1:1) is recrystallized from alcohol and then has a melting point of 148°-150° C. 150 mg. of 1-(p-methoxybenzoyl)pyrrolin-2-one are dissolved in 100 ml. of ethyl acetate and hydrogenated over 30 mg. of 5percent palladium/carbon with hydrogen at atmospheric pressure and room temperature. After filtering off the catalyst and evaporating the solvent, there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone.

Synthesize Find similar

Rx-ID: 25113901 Find similar reactions

Synthesize Find similar

With lithium hydroxide in water; ethyl acetate; benzene

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

12:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 12 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 276 mg. of lithium hydride (98percent), 40 ml. of benzene and 4.2 g. of 2-methoxypyrroline are boiled at reflux for 2 hours under nitrogen and while stirring well. After cooling to 25° C., 6.6 g. of p-methoxybenzoyl chloride dissolved in 25 ml. of benzene are added and the resulting mixture is stirred under reflux for 2 hours and at room temperature for 16 hours. 100 ml. of ethyl acetate followed by 3.0 g. of lithium hydroxide (98percent) dissolved in 25 ml. of water are added to the mixture at room temperature within 15 minutes. The organic phase is washed neutral with water, dried over sodium sulfate and evaporated under reduced pressure. After recrystallization from ethanol, there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 119°-120° C. Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

in ethanol; ethyl acetate; benzene

Hide Experimental Procedure

Title/Abstract Full Text Show Details

13:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 13 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 4.2 g. of 2-methoxypyrroline are dissolved in 25 ml. of benzene and treated at room temperature with 6.6 g. of p-methoxybenzoyl chloride dissolved in 30 ml. of benzene. The mixture is stirred at room temperature for 60 minutes and at reflux for 4 hours. 30 ml. of benzene are then added and the mixture is boiled at reflux for a further 24 hours. The volatile constituents are distilled off, the residue is taken up in ethanol, the mixture is concentrated, the residue is triturated with diethyl ether, filtered and the filter cake is taken up in ethyl acetate. The ethyl acetate solution is washed with sodium bicarbonate solution and water, dried over sodium sulfate and concentrated. The residue is sublimed in vacuo and there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 119°-120° C.

Synthesize Find similar

Rx-ID: 34023556 Find similar reactions

40%

Synthesize Find similar

With Shvo's Catalyst in toluene

T=100°C; 24 h; Inert atmosphere;

Zhang, Jian; Hong, Soon Hyeok

Organic Letters, 2012 , vol. 14, # 17 p. 4646 - 4649 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 25110901 Find similar reactions

With thionyl chloride in dichloromethane; toluene

Synthesize Find similar

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

11:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 11 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 20.0 g. of 4-(p-methoxybenzoylamino)butyric acid, 50 ml. of toluene and 9.2 ml. of thionyl chloride are heated at reflux for 2 hours and then the mixture is treated with decolorizing charcoal and evaporated. The residue is dissolved in methylene chloride and chromatographed over neutral aluminum oxide. The 1-(p-methoxybenzoyl)-2-pyrrolidinone, which is eluted with methylene chloride, is recrystallized from alcohol and has a melting point of 119°-120° C.

Synthesize Find similar

Rx-ID: 25113899 Find similar reactions

Synthesize Find similar

With hydrogenchloride; sodium hydroxide; phosphoric acid in P2O5; water; acetone; Petroleum ether; [14C]-4-Aminobutyric acid

Hide Experimental Procedure

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ; Title/Abstract Full Text Show Details

10:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 10 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 10.2 g. of p-methoxybenzoyl chloride are added at 30° C. in one portion while stirring well to 30.9 g. of 4-amino-butyric acid, 24.0 g. of sodium hydroxide and 300 ml. of ion-free water. After 2 hours, the mixture is acidified with 75 ml. of concentrated hydrochloric acid at a temperature below 10° C. The precipitate is filtered off, washed ion-free with water, dried in a drying oven at 65° C. over phosphorus pentoxide and then recrystallized from 45 ml. of acetone/low-boiling petroleum ether (3:1). There is obtained 4-(p-methoxybenzoylamino)butyric acid having a melting point of 120.5°-122° C. 10 g. of phosphorus pentoxide and 6 ml. of orthophosphoric acid (at least 85percent) are warmed with one another. 2.0 g. of 4-(p-methoxybenzoylamino)butyric acid are added at room temperature to the resulting solution. The mixture is warmed to 50° C. for 60 minutes, subsequently treated with ice and extracted with ethyl acetate. The organic phase is washed first with cold water, then with cold sodium bicarbonate solution and finally again with water and dried over sodium sulfate. The residue is triturated with diethyl ether and there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 120°-122° C.

Synthesize Find similar

Rx-ID: 25118868 Find similar reactions

With acetic acid in N-methyl-acetamide; ethanol

Hide Experimental Procedure

7:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 7

Synthesize Find similar

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ; Title/Abstract Full Text Show Details

Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 7.0 g. of the sodium salt of 2-pyrrolidinone (prepared using sodium hydride) suspended in 120 ml. of dimethylformamide are added at -10° C. to a solution of 20.0 g. of p-methoxybenzoic acid pentachlorophenyl ester in 100 ml. of dimethylformamide. Subsequently, the mixture is stirred at room temperature for 1 hour and at 55° C. for 8 hours. The solvent is evaporated, the residue is treated with cold aqueous acetic acid solution and the mixture is extracted with ethyl acetate. The organic phase is washed with cold sodium bicarbonate solution and water, dried over sodium sulfate, filtered and evaporated. The residue is taken up in ethanol and stirred in an ice bath. The separated crystals are filtered off and there is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 119°-120° C.

Synthesize Find similar 70%

Synthesize Find similar

Rx-ID: 4880574 Find similar reactions

With CrO3-3.5-dimethylpyrazole in dichloromethane

24 h; Ambient temperature;

Blay, Gonzalo; Cardona, Luz; Garcia, Begona; Garcia, Cristina L.; Pedro, Jose R.

Tetrahedron Letters, 1997 , vol. 38, # 47 p. 8257 - 8260 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 25132052 Find similar reactions

Synthesize Find similar

in tetrahydrofuran

Hide Experimental Procedure

8:Preparation of 1-(p-benzyloxybenzoyl)-2-pyrrolidinone

150 mg. of 1-(p-hydroxybenzoyl)-2-pyrrolidinone are dissolved in 7 ml. of absolute tetrahydrofuran and then etheric diazomethane solution is added. The solvents are distilled off, the residue is triturated with diethyl ether and the mixture is filtered. There is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone which melts at 117.5°-119° C. after sublimation.

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ; Title/Abstract Full Text Show Details

Synthesize Find similar

Rx-ID: 25113891 Find similar reactions

Synthesize Find similar

in N-methyl-acetamide; P2O5; diethyl ether

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

2:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 2 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 20.2 g. of the sodium salt of 2-pyrrolidinone (prepared using sodium hydride) suspended in 270 ml. of dimethylformamide are added in four portions at -10° C. to a solution of 37.0 g. of p-methoxybenzoyl chloride in 50 ml. of dimethylformamide. Subsequently, the mixture is stirred at room temperature for 1 hour and then at 40° C. for 4 hours. The solvent is evaporated and the residue is treated with diethyl ether and with cold sodium bicarbonate solution. The insoluble crystalline constituents are filtered off, washed with water and diethyl ether and dried in vacuo over phosphorus pentoxide. There is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 120°-121° C.

Synthesize Find similar

Rx-ID: 25113900 Find similar reactions

Synthesize Find similar

Hoffmann-La Roche Inc.

Patent: US4369139 A1, 1983 ;

in diethyl ether

Hide Experimental Procedure

Title/Abstract Full Text Show Details

6:Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone

EXAMPLE 6 Preparation of 1-(p-methoxybenzoyl)-2-pyrrolidinone 24.4 g. of p-methoxybenzoyl chloride and 22.5 g. of 1-trimethylsilyl-2-pyrrolidinone are mixed and the mixture is stirred at room temperature for 10 minutes. Then, the resulting trimethylchlorosilane is distilled off under reduced pressure in an oil bath at 80° C. The residue is triturated with 100 ml. of diethyl ether. The mixture is filtered and the filter cake is recrystallized from ethanol. There is obtained 1-(p-methoxybenzoyl)-2-pyrrolidinone having a melting point of 120°-121° C.

Synthesize Find similar

Rx-ID: 8800508 Find similar reactions

Synthesize Find similar

With tetrakis(triphenylphosphine) palladium(0) in tetrahydrofuran

T=200°C; 0.0833333 h;

Synthesize Find similar

Karimi; Kihlberg; Langstroem

Journal of the Chemical Society. Perkin Transactions 1, 2001 , # 13 p. 1528 - 1531 Title/Abstract Full Text View citing articles Show Details