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Chemical Structure| 108-27-0
Chemical Structure| 108-27-0
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Product Details of [ 108-27-0 ]

CAS No. :108-27-0 MDL No. :MFCD00005273
Formula : C5H9NO Boiling Point : -
Linear Structure Formula :- InChI Key :YVIVRJLWYJGJTJ-UHFFFAOYSA-N
M.W : 99.13 Pubchem ID :66055
Synonyms :

Safety of [ 108-27-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 108-27-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 108-27-0 ]

[ 108-27-0 ] Synthesis Path-Downstream   1~59

  • 2
  • [ 123-76-2 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
99% Stage #1: levulinic acid With C24H22N4*BF4(1-)*Ru(2+)*Cl(1-)*C10H14; ammonium formate In neat (no solvent) at 80℃; for 4h; Green chemistry; Stage #2: at 120℃; for 20h; Green chemistry;
97% With water; ammonium formate at 160℃; for 3h; Autoclave; Green chemistry;
95.2% With ammonium formate In water at 180℃; for 3h; Autoclave; Inert atmosphere; 1-13 Example 2: General procedure: Take 0.5 g of levulinic acid and 1 g of ammonium formate in a beaker, add 10 mL of water, dissolve, add the solution to a 25 mL autoclave, and add 0.05 g of a Pd-Ni / C catalyst (Pd, Ni mass) The ratio is 1: 1), purged with nitrogen five times, the reaction temperature is 180 ° C, and the reaction is performed for 3 hours to obtain 5-methyl-2-pyrrolidone.The yield was 94.5%.
89% With platinum on carbon; ammonia; hydrogen In methanol at 25℃; for 72h;
85% With ammonium hydroxide; formic acid; diethylene glycol dimethyl ether In water at 130℃; for 16h; Inert atmosphere; Autoclave;
With ammonia; water; nickel at 130 - 160℃; Hydrogenation.Anfangsdruck;
With ammonia; water; nickel at 270℃; Hydrogenation;
With ammonium formate In water at 180℃; for 3h; Autoclave; High pressure; 1.2. General procedure for the reductive amination of levulinic acid to 5-methyl-2-pyrrolidone (2) using ammonium formate and Raney-Ni catalyst under thermal conditions General procedure: A mixture of levulinic acid (116 mg, 1.0 mmol), ammonium formate (1.0 - 4.0 mmol) and Raney -Ni (20 mg), was prepared in a 25 mL stainless steel solvothermal reaction kettle with a Teflon inner sleeve and then 2.0 mL of de-ionized water was added. The reaction kettle was firmly closed and heated in a thermostated convection oven maintained at 120-180 °C for 2-24 h. At the end of the heating period the kettle was removed from the oven and cooled to room temperature. The liquid fraction was diluted with 5 mL of de-ionized water, separated from the catalyst by centrifuging at 1700X g for 5 minutes and the product was extracted to methylene chloride (3x 5 mL). The combined methylene chloride layer was concentrated under reduced pressure to give the products.
96.3 %Chromat. With ammonium hydroxide; 5%-palladium/activated carbon; hydrogen In water at 200℃; Autoclave; Green chemistry;
Multi-step reaction with 2 steps 1: borane-ammonia complex; ammonia; methanol / 12 h / 120 °C / Autoclave; Green chemistry 2: borane-ammonia complex; ammonia; methanol / 120 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry
Multi-step reaction with 2 steps 1: borane-ammonia complex; ammonia; methanol / 2 h / 100 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry 2: borane-ammonia complex; ammonia; methanol / 120 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry
Multi-step reaction with 2 steps 1: borane-ammonia complex; ammonia; methanol / 2 h / 20 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry 2: borane-ammonia complex; ammonia; methanol / 120 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry
Multi-step reaction with 2 steps 1: borane-ammonia complex; ammonia; methanol / 8 h / 120 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry 2: borane-ammonia complex; ammonia; methanol / 120 °C / Inert atmosphere; Schlenk technique; Glovebox; Green chemistry

Reference: [1]Sun, Zheming; Chen, Jiangbo; Tu, Tao [Green Chemistry, 2017, vol. 19, # 3, p. 789 - 794]
[2]Li, Hu; Wu, Hongguo; Zhang, Heng; Su, Yaqiong; Yang, Song; Hensen, Emiel J. M. [ChemSusChem, 2019, vol. 12, # 16, p. 3778 - 3784]
[3]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN110615754, 2019, A Location in patent: Paragraph 0033-0050
[4]Xie, Chao; Song, Jinliang; Wu, Haoran; Hu, Yue; Liu, Huizhen; Zhang, Zhanrong; Zhang, Pei; Chen, Bingfeng; Han, Buxing [Journal of the American Chemical Society, 2019, vol. 141, # 9, p. 4002 - 4009]
[5]Du, Xian-Long; He, Lin; Zhao, She; Liu, Yong-Mei; Cao, Yong; He, He-Yong; Fan, Kang-Nian [Angewandte Chemie - International Edition, 2011, vol. 50, # 34, p. 7815 - 7819]
[6]Hayashi; Hachihama [Kogyo Kagaku zasshi / Journal of the Society of Chemical Industry, 1954, vol. 57, p. 127][Chem.Abstr., 1955, p. 11554] Hachihama; Hayashi [Technology Reports of the Osaka University, 1954, vol. 4, p. 173,176]
[7]Current Patent Assignee: PEPSICO INC - US2681349, 1952, A
[8]Amarasekara, Ananda S.; Lawrence, Yen Maroney [Tetrahedron Letters, 2018, vol. 59, # 19, p. 1832 - 1835]
[9]Haus, Moritz O.; Hofmann, Jan P.; Konrad, Marc; Louven, Yannik; Palkovits, Regina [Green Chemistry, 2020, vol. 22, # 14, p. 4532 - 4540]
[10]Meier, Sebastian; Riisager, Anders; Yang, Song; Zhao, Wenfeng [Green Chemistry, 2020, vol. 22, # 18, p. 5972 - 5977]
[11]Meier, Sebastian; Riisager, Anders; Yang, Song; Zhao, Wenfeng [Green Chemistry, 2020, vol. 22, # 18, p. 5972 - 5977]
[12]Meier, Sebastian; Riisager, Anders; Yang, Song; Zhao, Wenfeng [Green Chemistry, 2020, vol. 22, # 18, p. 5972 - 5977]
[13]Meier, Sebastian; Riisager, Anders; Yang, Song; Zhao, Wenfeng [Green Chemistry, 2020, vol. 22, # 18, p. 5972 - 5977]
  • 3
  • [ 108-27-0 ]
  • [ 349548-27-2 ]
YieldReaction ConditionsOperation in experiment
90% With barium dihydroxide
76% With hydrogenchloride for 8h; Heating;
With hydrogenchloride Heating;
With sodium hydroxide for 6h; Heating;
With hydrogenchloride In water Heating / reflux; 12 A solution of 5-methyl-2-pyrrolidinone (20 g, 0.20 mol) in 6 NHC1 (250mL) was heated to reflux overnight, and concentrated to give crude4-aminopentanoic acid. The crude product was taken up into 1 NNaOH (440mL)/THF (440 mL), and treated with(BOC) 20 (70 g, 0.32 mol). The reaction mixture was left to stir overnight, and concentrated. The residue was washed with Et2O (x 3), acidified with 1 N KHSO4 solution, and extracted withCH2C12 (x 3). The combined organics were dried(Na2SO4), and concentrated to give crude 4-[(tert-butoxycarbonyl) amino] pentanoic acid as a whitesolid. 1H NMR (CDC13,500 MHz) 8 4.43 (br s, 1H), 3.74 (br s,1H), 2.44 (t, 2H), 1.84(m,1H), 1.72(m, 1H), 1.47 (s, 9H), 1.18 (d, 3H).

  • 4
  • [ 75-91-2 ]
  • [ 108-27-0 ]
  • [ 130147-39-6 ]
YieldReaction ConditionsOperation in experiment
80% With tris(triphenylphosphine)ruthenium(II) chloride In benzene Ambient temperature;
  • 5
  • [ 108-27-0 ]
  • [ 98-59-9 ]
  • [ 138816-53-2 ]
YieldReaction ConditionsOperation in experiment
69% Stage #1: 5-methylpyrrolidin-2-one With n-butyllithium; hexamethyldisilazide In tetrahydrofuran; hexane at -20℃; for 1h; Inert atmosphere; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran; hexane at -20 - 20℃; Inert atmosphere;
60% With sodium hydride In tetrahydrofuran at 0℃;
Stage #1: 5-methylpyrrolidin-2-one With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Inert atmosphere; Stage #2: p-toluenesulfonyl chloride In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; Inert atmosphere;
  • 6
  • [ 5457-24-9 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
70% With hydrogen In ethanol at 150℃; for 7h;
  • 7
  • [ 591-12-8 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
75% With ammonia; hydrogen In ethanol at 120 - 150℃;
  • 8
  • [ 108-27-0 ]
  • [ 448-97-5 ]
  • 3,3'-Difluoro-N4,N4'-bis-[5-methyl-pyrrolidin-(2Z)-ylidene]-biphenyl-4,4'-diamine [ No CAS ]
  • 9
  • [ 108-27-0 ]
  • [ 24424-99-5 ]
  • [ 128372-77-0 ]
YieldReaction ConditionsOperation in experiment
90% In acetonitrile at 20℃; for 7h; a a) N-Boc-5-methyl-2-pyrrolidinone; A solution of di-tert-butyl carbonate (12.1 g; 55.5 mmol) in acetonitrile (20 mL) was added dropwise to a solution of 5-methyl-2-pyrrolidinone (5.0 g; 50 mmol) and 4-dimethylamino-pyridine (0.31 g; 5 mol%) in acetonitrile (50 mL) at RT. The mixture was stirred for 7 hrs. The solvent evaporated and the obtained crude dissolved in ethyl acetate and washed with NaHCO3 sat. solution. The organic layer was collected and dried (Na2SO4) and evaporation of the solvent gave the clean product.9.41 g; 90%C10HnNO3 calculated 199; found 126/144Lc Rt (5 min)= 1.73, 99% NMR (400 MHz, dmso-d6): 1.22 (3H, d, J= 6.4 Hz); 1.43 (9H, s);1.50-1.57 (IH, m); 2.04-2.14 (IH, m); 2.26 (IH, ddd, J= 3.2 Hz, 9.2 Hz, 17.2 Hz); 2.56 (IH, ddd, J= 9.2 Hz, 10.42 Hz, 17.2 Hz); 4.07-4.15 (IH, m).
86% With lithium diisopropyl amide In tetrahydrofuran at -78℃;
  • 10
  • [ 108-27-0 ]
  • [ 38762-41-3 ]
  • (4-bromo-2-chloro-phenyl)-(5-methyl-4,5-dihydro-3<i>H</i>-pyrrol-2-yl)-amine [ No CAS ]
  • 12
  • [ 123-76-2 ]
  • [ 74-89-5 ]
  • [ 5075-92-3 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
1: 91% 2: 4.6% With ammonia; hydrogen In water at 150℃; for 4h; Batch Reduction of Levulinic Acid-NH4 salt to 1,5-Dimethyl-2-Pyrrolidone A 300 ml stainless steel Autoclave Engineers magnedrive packless autoclave equipped with thermocouple, cooling coils, sample dip tube containing a stainless steel 5 μm Mott filter and Dispersimix turbine type draft tube agitator containing a rotating impeller was employed for the batch hydrogenation of levulinic acid to 1,5-dimethyl-2-pyrrolidone. The autoclave was charged with 50 g (0.42 mole) levulinic acid (98%), 25 g (0.42 mole) of 29% aqueous ammonia and 37 g (0.48 mole) monomethylamine. Three grams of a 5% Pd/C (Engelhard ESCAT 112) slurry catalyst was then added to the vessel. The vessel was closed and purged twice with nitrogen followed by three purges with hydrogen. The reactor was set to 0.34 MPa with hydrogen with slow stirring and heated to 150° C. At temperature, the pressure was raised to 4.14 MPa and maximum stirring commenced. After 4 hr, the reactor was stopped and cooled, followed by filtration of the catalyst from the reaction product. [0095] Analysis of the product mixture was performed by gas chromatography (HP 6890; Agilent, Palo Alto, Calif.) employing a DB1701 megabore column (5% crosslinked phenyl-methyl-silicone; 30 m long, 0.33 m, ID, and 0.25 μm film thickness; J & W Scientific, Folsom, Calif.) and a flame ionization detector. The temperature was initially held at 60° C. for 2 min. and then heated at 8° C./min to 230° C. for 15 min. The column flow rate was 1.5 cc/min He. The injector and detector temperatures were 250° C. and 265° C., respectively. GC analysis showed complete conversion of levulinic acid and selectivities of 91% and 4.6%, respectively of 1,5-dimethyl-2-pyrrolidone and 5-methyl-2-pyrrolidone. Two high boiler amides amounting to 4.4% selectivity were also produced
  • 13
  • levulinic acid ammonium salt [ No CAS ]
  • [ 74-89-5 ]
  • [ 5075-92-3 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
1: 94% 2: 3.9% With hydrogen In water at 150℃; Continuous Reduction of Levulinic Acid-NH4 Salt to 1,5-Dimethyl-2-Pyrrolidone A stainless steel fixed-bed reactor (0.50 ID×36) was charged with 80 ml (64 g) of 0.7% Pd on 2.5 mm carbon granules (Engelhard 859A-1-563-1). Separate feeds of monomethylamine and a 68% aqueous solution of levulinic acid (as the ammonium salt) were fed to the top of the reactor at a rate of 8.3 g/hr and 17.3 g/hr, respectively, together with 76 SCCM hydrogen gas to continuously carry out the amination and cyclization. The reduction was performed continuously at 150° C. and 3.45 MPa for a total of 367 hr with a productivity of 91 g levulinic acid/g catalyst/hr. Samples were taken every 24 hr and analyzed by gas chromatography employing an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a DB1701 megabore column (5% crosslinked phenyl-methyl-silicone; 30 m long, 0.33 m ID, and 0.25 μm film thickness; J & W Scientific, Folsom, Calif.) and a flame ionization detector. The GC temperature program was initially held at 60° C. for 2 min, and then heated at 8° C./min to 230° C. for 15 min. The column flow rate was 1.5 cc/min He. The injector and detector temperatures were 250° C. and 265° C., respectively. Product identification was made by GC/MS on a Finnigan MAT 4510B GC/MS having direct probe capability and employing a mass range of 1000 au (atomic units). GC analysis of a product sample showed a 99% conversion of levulinic acid and 94% yield of 1,5-dimethyl-2-pyrrolidone and 3.9% yield of 5-methyl-2-pyrrolidone
  • 14
  • levulinic acid ammonium salt [ No CAS ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
0.1% With hydrogen In water at 150℃; for 4 - 17h; 1; 2; 7; 8 Examples 1-12; Preparation of 5-Methyl-2-Pyrrolidone (MP) The feedstock used herein was 72% aqueous solution (by weight) of the ammonium salt of levulinic acid (LA/aq. NH4OH(28%)). The temperature and pressure of the reactions were maintained at 150° C. and 6.9 MPa. Water was used as the solvent medium for the reaction. The results are set forth in the following table
0.43% With hydrogen In water at 150℃; for 4 - 17h; 5; 11 Examples 1-12; Preparation of 5-Methyl-2-Pyrrolidone (MP) The feedstock used herein was 72% aqueous solution (by weight) of the ammonium salt of levulinic acid (LA/aq. NH4OH(28%)). The temperature and pressure of the reactions were maintained at 150° C. and 6.9 MPa. Water was used as the solvent medium for the reaction. The results are set forth in the following table
0.15% With hydrogen In water at 150℃; for 4 - 17h; 3; 4; 9; 10 Examples 1-12; Preparation of 5-Methyl-2-Pyrrolidone (MP) The feedstock used herein was 72% aqueous solution (by weight) of the ammonium salt of levulinic acid (LA/aq. NH4OH(28%)). The temperature and pressure of the reactions were maintained at 150° C. and 6.9 MPa. Water was used as the solvent medium for the reaction. The results are set forth in the following table
0.4% With hydrogen In water at 150℃; for 4 - 17h; 6; 12 Examples 1-12; Preparation of 5-Methyl-2-Pyrrolidone (MP) The feedstock used herein was 72% aqueous solution (by weight) of the ammonium salt of levulinic acid (LA/aq. NH4OH(28%)). The temperature and pressure of the reactions were maintained at 150° C. and 6.9 MPa. Water was used as the solvent medium for the reaction. The results are set forth in the following table

  • 15
  • [ 108-91-8 ]
  • [ 539-88-8 ]
  • [ 18518-40-6 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogen In 1,4-dioxane at 150℃; for 4 - 8h; 71; 88 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 77 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 72 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 78 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 83 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 80 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 79 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 81 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 74 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 85 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 82 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 73 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 75 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 76 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 84 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 86 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 87 Examples 71-88; Preparation of 5-Methyl-N-Cyclohexyl-2-Pyrrolidone (MCHP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Cyclohexylamine (CHA) as the Alkyl Amine [0075] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 25% aryl or alkyl amine and 45% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette from the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0085] The reaction temperature was 150° C.; the reactions were carried out for 4 hrs. at a pressure of 5.52 MPa, except for Ex. 88. Ex. 88 was carried out at 150° C. and 6.90 MPa for a period of 8 hrs. The results are set forth in the following table. Abbreviations: Con, conversion; Sel, selectivity.

Reference: [1]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[3]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[4]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[5]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[6]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[7]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[8]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[9]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[10]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[11]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[12]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[13]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[14]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[15]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[16]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
[17]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192938, 2004, A1 Location in patent: Page 10
  • 16
  • [ 539-88-8 ]
  • [ 107-12-0 ]
  • [ 38286-46-3 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogen In 1,4-dioxane at 150℃; for 4h; 13 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 19 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 14 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 20 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 26 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 22 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 21 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 23 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 24 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 16 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 28 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 25 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 15 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 17 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 18 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 27 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 29 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.
With hydrogen In 1,4-dioxane at 150℃; for 4h; 30 Examples 13-30; Preparation of 5-Methyl-N-Propyl-2-Pyrrolidone (PrMP) and 5-Methyl-2-Pyrrolidone (MP) by Batch Reduction of Ethyl Levulinate (EL) Using Propiionitrile (PN) as the Alkyl Cyano Compound [0087] To a 5 ml pressure vessel was added 50 gm of catalyst, and 1 gm of a solution containing 30 wt % ethyl levulinate, 22% aryl cyano compound and 48% dioxane. The vessel was sealed, charged with 5.52 MPa hydrogen and heated to 150° C. for 4 hours. The pressure was maintained at 5.52 MPa during the course of the reaction. At the end of the reaction, the vessel was rapidly cooled in ice, vented and an internal GC standard of methoxyethylether was added. The solution was separated by pipette form the catalyst and analyzed by GC-MS using an HP 6890 (Agilent; Palo Alto, Calif.) equipped with a FFAP 7717 (30 meter) column. The results set forth in the tables below are based on area %.[0090] The reactions were carried out for 4 hours at a temperature and pressure of 150° C. and 5.52 MPa, respectively. The feedstock was ethyl livulinate/propionitrile/dioxane at a ratio (wt. %) of 30/15/55. The results are set forth in the following table.

Reference: [1]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[3]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[4]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[5]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[6]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[7]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[8]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[9]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[10]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[11]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[12]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[13]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[14]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[15]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[16]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[17]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
[18]Current Patent Assignee: DUPONT DE NEMOURS INC - US2004/192935, 2004, A1 Location in patent: Page 7
  • 17
  • [ 720691-59-8 ]
  • [ 108-27-0 ]
  • 1-{6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-5-methyl-2-pyrrolidinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In 1,4-dioxane at 175℃; for 0.25h; microwave reactor; 250 3-CYCLOBUTYL-7- [ (5-IODO-2-PYRIDINYL) oxy] -2,3, 4, 5-TETRAHYDRO-1 H-3-BENZAZEPINE (E207) (294 mg, 0.7 MMOL) 1,10 phenanthroline (38 mg, 0.2 MMOL), 5-METHYL-2-PYRROLIDINONE (139 mg 1.4 MMOL) were dissolved in dioxane (2ml). Copper (L) LODIDE (39 mg, 0.2 MMOL) and caesium carbonate (479 MG, 1.5 MMOL) were added and the mixture heated in a microwave reactor at 175°C for 15 minutes. The mixture was cooled and filtered through celite, washing through with dichloromethane. The filtrate was concentrated in vacuo and the crude material purified by column chromatography, eluting with dichloromethane through to a mixture of. 880 ammonia: methanol : DICHLOROMETHANE (1: 9: 90) to afford the title compound (137 mg); MS (ES+) m/e 392 [M+H] +.
  • 18
  • [ 108-27-0 ]
  • [ 612-12-4 ]
  • [ 155956-98-2 ]
YieldReaction ConditionsOperation in experiment
40% With hydrogenchloride; NaH In tetrahydrofuran; hexane; dimethyl sulfoxide 3 1-[[2-[[1-[2-(1-Methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidin-2-one Hydrochloride (3:2) (CP #3) EXAMPLE 3 1-[[2-[[1-[2-(1-Methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidin-2-one Hydrochloride (3:2) (CP #3) A solution of γ-valerolactam (7 g, 70.5 mmol) in THF (150 mL) and DMSO (20 mL) was treated with NaH (2.83 g of a 60% oil dispersion) at 0° C. under nitrogen atmosphere. After a total of 15 min, α,α'-dichloro-o-xylene (25 g, 140 mmol) was added and the solution was allowed to warm and stir at room temperature. After 4 h, 100 mL of ether and 100 mL of 0.2 N HCl were added. The water was withdrawn, and the organic layer was washed 2* more with water, dried (MgSO4), filtered and concentrated. This material was purified on ca. 400 g of silica gel (flash chromatography; EtOAc/hexane 7:3) to yield N-[2-(chloromethyl)benzyl]-γ-valerolactam (6.6 g, 40%).
  • 19
  • [ 108-27-0 ]
  • [ 626-16-4 ]
  • [ 54013-91-1 ]
  • 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidin-2-one hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% With hydrogenchloride; n-butyllithium; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; hexane; water; isopropyl alcohol; EXAMPLE 1 1-[[3-[[1-[2-(1-Methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidin-2-one Hydrochloride (3:2) (CP #1) A solution of N-[2-(1-methylethoxy)phenyl]piperazine (11.95 g, 54.3 mmol, prepared as described by Martin and Scott, et. al. J. Med. Chem., 1989, 32, 1052-1056), in THF (250 mL) was treated with alpha,alpha'-dichloro-m-xylene (23.7 mL, 0.163 mol) and refluxed. After 4 h, diisopropylethylamine (10.4 mL, 55 mmol) was added and the solution was refluxed an additional 1.5 h. Treatment with 1N HCl (120 mL), water (50 mL), and ether (200 mL) caused a white solid to form which was collected by filtration. This material (7.40 g, 18.73 mmol) was partitioned into saturated aqueous NaHCO3 to give 6.0 g of an oil. A solution of this material in THF (10 mL) was added to a solution of gamma-valerolactam (1.74 g, 17.5 mmol) in THF (80 mL) which had been treated at 0 C. with 2.5 M n-BuLi/hexane (7.0 mL. 1 mol-eqiv). The resulting solution was heated at reflux for 1.5 h, treated with a suspension of gammavalerolactam (500 mg, 5.05 mmol) and 2.5 M n-BuLi/hexane (2.0 mL) in THF (10 mL) and refluxed an additional hour. The solution was cooled and partitioned between water and ether. The ether layer was separated, dried, filtered, and concentrated to give a yellow oil. This material was purified on two Waters Prep-500 silica gel columns (EtOAc/hexane; 8:2), affording 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]-methyl-piperidin-2-one as an oil, 4.80 g. A solution of this oil in i-PrOH (30 mL) was treated with conc HCI (1.15 mL) followed by ether (ca. 500 mL). A white solid was collected by filtration and recrystallized from i-PrOH/ether affording 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidin-2-one hydrochloride (3:2) as a white crystalline solid (3.74 g, 44%), m.p. 206-208 C. Both 1 H-NMR and FAB-MS supported the assigned structure. Elemental Analysis: Calculated for C26 H35 N3 O2.1.5 HCl: C, 65.57; H, 7.72; N, 8.82; Cl, 11.17. Found: C, 65.29; H, 7.78; N, 8.68; Cl, 10.95.
44% With hydrogenchloride; n-butyllithium; conc HCl; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; hexane; water; isopropyl alcohol; EXAMPLE 1 1-[[3-[[1-[2-(1-Methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]piperidin-2-one Hydrochloride (3:2) (CP #1) A solution of N-[2-(1-methylethoxy)phenyl]piperazine (11.95 g, 54.3 mmol, prepared as described by Martin and Scott, et. al. J. Med. Chem., 1989, 32, 1052-1056), in THF (250 mL) was treated with alpha,alpha'-dichloro-m-xylene (23.7 mL, 0.163 mol) and refluxed. After 4 h, diisopropylethylamine (10.4 mL, 55 mmol) was added and the solution was refluxed an additional 1.5 h. Treatment with 1N HCl (120 mL), water (50 mL), and ether (200 mL) caused a white solid to form which was collected by filtration. This material (7.40 g, 18.73 mmol) was partitioned into saturated aqueous NaHCO3 to give 6.0 g of an oil. A solution of this material in THF (10 mL) was added to a solution of gamma-valerolactam (1.74 g, 17.5 mmol) in THF (80 mL) which had been treated at 0 C. with 2.5M n-BuLi/hexane (7.0 mL. 1 mol-eqiv). The resulting solution was heated at reflux for 1.5 h, treated with a suspension of gammavalerolactam (500 mg, 5.05 mmol) and 2.5M n-BuLi/hexane (2.0 mL) in THF (10 mL) and refluxed an additional hour. The solution was cooled and partitioned between water and ether. The ether layer was separated, dried, filtered, and concentrated to give a yellow oil. This material was purified on two Waters Prep-500 silica gel columns (EtOAc/hexane; 8:2), affording 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]-methyl-piperidin-2-one as an oil, 4.80 g. A solution of this oil in i-PrOH (30 mL) was treated with conc HCl (1.15 mL) followed by ether (ca. 500 mL). A white solid was collected by filtration and recrystallized from i-PrOH/ether affording 1-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-piperidin-2-one hydrochloride (3:2) as a white crystalline solid (3.74 g, 44%), m.p. 206-208 C. Both 1 H-NMR and FAB-MS supported the assigned structure. Elemental Analysis: Calculated for C26 H35 N3 O2.1.5 HCl: C, 65.57; H, 7.72 N, 8.82; Cl, 11.17. Found: C, 65.29; H, 7.78; N, 8.68; Cl, 10.95.
  • 20
  • [ 108-27-0 ]
  • [ 1771-18-2 ]
  • [ 59701-43-8 ]
YieldReaction ConditionsOperation in experiment
8.6% With trichlorophosphate; In 1,2-dichloro-ethane; EXAMPLE 5 Reaction of 5-methyl-2-pyrrolidinone, <strong>[1771-18-2]2-methoxyphenothiazine</strong> and phosphorus oxychloride in 1,2-dichloroethane according to the procedure of Example 4 affords 2-METHOXY-10-[5-METHYL-1-(5-METHYL-1-PYRROLIN-2-YL)-2-PYRROLIN-2-YL]PHENOTHIAZINE HYDROCHLORIDE (8.6% yield), m.p. 236.5-238.5 C. (corr.), from ethanol-ether.
  • 21
  • [ 108-27-0 ]
  • [ 100707-08-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In water at 100℃; for 15h; X-900-C 5-Methyl-2-pyrrolidinone (5.09 g, 51.35 mmol) was stirred 15 hours in 6N aqueous hydrochloric acid (75 mL) at 100° C. The solution was concentrated under reduced pressure to yield a white solid that was redissolved in methanol (100 mL) to which thionyl chloride (3.75 mL, 51.54 mmol, 1.00 equiv.) was slowly added. After 1 hour at room temperature, the solution was concentrated under reduced pressure and the resulting crude ester was redissolved in anhydrous dichloromethane (100 mL). Triethylamine (21.5 mL, 154 mmol, 3.00 equiv.) was added, followed by di-tert-butyldicarbonate (16.88 g, 77.3 mmol, 1.51 equiv.), and the resulting solution was stirred 2 days at room temperature. The opaque yellow solution was diluted with water (100 mL), and the two phases were mixed and separated. The aqueous phase was extracted with dichloromethane (2×100 mL), and the combined extracts were washed with brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield an orange oil (11.13 g, 94% yield.)
  • 22
  • [ 108-27-0 ]
  • [ 100-39-0 ]
  • 5-methyl-1-(phenylmethyl)-2-pyrrolidinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: 5-methylpyrrolidin-2-one With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.25h; Stage #2: benzyl bromide In N,N-dimethyl-formamide; mineral oil at 20℃; for 16h; PREPARATION OF INTERMEDIATE 45 NaH (60% dispersion in mineral oil) (444 mg, 11.10 mmol) was added to a stirred solution of 5-methylpyrrolidin-2-one (CAS: 108-27-0; 1 g, 10.09 mmol) in DMF (15 mL) at rt. The mixture was stirred at rt for 15 min and then nenzyl bromide (1.32 mL, 11.10 mmol) was added. The mixture was stirred at rt for 16 h. Then NH4CI aq. sat. sltn. was added and the mixture was extracted with Et20. The organic layer was separated, dried (MgS04), filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica; 7M ammonia solution in methanol in DCM 0/100 to 5/95). The desired fractions were collected and concentrated in vacuo to yield intermediate 45 (1.72 g, 90%) as an oil.
88% With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; Inert atmosphere; 7.1 Step 1:
Synthesis of I-Benzyl-5-methyl-pyrrolidin-2-one (7a)
To a suspension of 5-methylpyrrolidin-2-one (4.6 g, 46.4 mmol) in DMF (30 mL) under a nitrogen atmosphere at 0°C, sodium hydride (60% in oil, 2.8 g, 70 mmol) and benzyl bromide (6.6 mL, 55.7 mmol) were added. After 16 hours of stirring at room temperature, the reaction was quenched with a saturated solution of ammonium chloride. Ethyl acetate was added and the organic layer was extracted twice with ethyl acetate, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc 7/3) to give compound (7a) as yellow oil (7.56 g, 40.0 mmol, 88%). 1H NMR (400 MHz, CDCl3) δ 1.20 (d, 3H), 1.60 (m, 1H), 2.15 (m, 1H), 2.40 (m, 1H), 2.55 (m, 1H), 3.50 (m, 1H), 4.00 (d, 1H), 5.00 (d, 1H), 7.40-7.20 (m, 5H). MS m/z ([M+H]+) 190.
88% With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 16h; Inert atmosphere; 39.1 Synthesis of l-Benzyl-5-methyl-pyrrolidin-2-one To a suspension of 5-methylpyrrolidin-2-one (4.6 g, 46.4 mmol) in DMF (30 mL) under a nitrogen atmosphere at 0°C, sodium hydride (60% in oil, 2.8 g, 70 mmol) and benzyl bromide (6.6 mL, 55.7 mmol) were added. After 16 hours of stirring at room temperature, the reaction was quenched with a saturated solution of ammonium chloride. Ethyl acetate was added and the organic layer was extracted twice with ethyl acetate, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (cyclohexane/EtOAc 7/3) to give compound (39a) as yellow oil (7.56 g, 40.0 mmol, 88%). lH NMR (400 MHz, CDC13) δ 1.20 (d, 3H), 1.60 (m, 1H), 2.15 (m, 1H), 2.40 (m, 1H), 2.55 (m, 1H), 3.50 (m, 1H), 4.00 (d, 1H), 5.00 (d, 1H), 7.40-7.20 (m, 5H). MS m/z ([M+H]+) 190.
86% With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 16h; 12.A j228j Part A. Preparation of 1-benzyl-5-methylpyrrolidin-2-one. Sodium hydride (60% suspension in mineral oil) (2.54 g, 63.6 mmol) was added to a solution of 5-methylpyrrolidin-2-one (4.2 g, 42.4 mmol) in N,N-dimethylformamidemL) at 0°C. Benzyl bromide (6.05 mL, 50.8 mmol) was then added and the resulting mixture was stirred for 16 h, while letting the temperature rise from 0°C to roomtemperature. A saturated aqueous solution of ammonium chloride (50 mL) was then slowly added and the product was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with a 5% aqueous solution of sodium hydrogen carbonate (100 mL), dried with magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a 100 g silica gel cartridge using agradient of 5 to 75% of EtOAc in hexanes to provide 1-benzyl-5-methylpyrrolidin-2-one (6.88 g, 86%) as an oil. ‘H NMR (300 MHz, CDC13): ppm 1.16 (d, J 6.25 Hz, 3 H),1.53 - 1.64 (m, 1 H), 2.04 -2.21 (m, 1 H), 2.34 - 2.56 (m, 2 H), 3.46 - 3.58 (m, 1 H), 3.98 (d, J 15.02 Hz, 1 H), 4.97 (d, J 15.02 Hz, 1 H), 7.21 - 7.35 (m, 5 H).
52.4% With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3h; Step 1. Synthesis of l-benzyl-5-methylpyrrolidin-2-one. To a stirred solution of 5-methylpyrrolidin-2-one (200 g, 2.02 mol, 1.0 eq) in DMF (1.5 L), sodium hydride (60% suspension on mineral oil, 131 g, 3.3 mol, 1.5 eq) was slowly added at 0 °C, followed by benzyl bromide (292 mL, 2.42 mol, 1.2 eq) and the mixture was allowed stir at room temperature for 3h. After completion of the reaction (monitored by TLC, 20%) ethyl acetate-hexane, KMn04, R = 0.45), the reaction was quenched by adding ice cubes and the mixture was extracted with ethyl acetate (500 mL). The organic extract was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluting with 10% ethyl acetate in hexanes to afford l-benzyl-5-methylpyrrolidin-2-one in two fractions. The first fraction contained 200 g of l-benzyl-5-methylpyrrolidin-2-one (yield 52.4 %, LC-MS: purity: 95%) and the second fraction contained an additional 100 g (yield 26.2 %, LC-MS: purity: 83%) as an oily liquid. (ES+): m/z 190.1 (M+H+); tr = 1.21, 1.61 min.
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; A A solution of 5-methylpyrrolidin-2-one (4.6 g, 46.4 mmol) at O0C in DMF (30 ml) was treated with 2.8 g (70 mmol) of NaH (60% dispersion in oil) and then 6.6 mL (55.7 mmol) of benzyl brominde. The solution was warmed to room temperature and allowed to stir overnight. The reaction was quenched with saturated aqueous NH4Cl, and extracted twice with EtOAc. The combined organic extracts were washed with saturated aqueous NaHCO3, then brine and dried over Na2SO4. The residue was purified on silica gel with EtOAc in hexanes to provide AJ. as a colorless oil. Data for AA : NMR (500 MHz, CDCl3): δ 7.4 - 7.2 (M, 5H), 5.0 (d, IH), 4.0(d, IH), 3.5 (m, IH), 2.55 (m, IH), 2.4 (m, IH), 2.15 (m, IH), 1.6 (m, IH), 1.2 (d, 3H) ppm.
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3h; 1 Reactions step 1: Synthesis of 1 -benzyl-5-methylpyrrolidin-2-one Reactions step 1: Synthesis of 1-benzyl-5-methylpyrrolidin-2-one To a stirred solution of 5-methylpyrrolidin-2-one (200 g, 2.02 mol, 1.0 eq) in DMF (1.5 L), sodium hydride (60% suspension on mineral oil, 131 g, 3.03 mol, 1.5 eq) was slowly added at 0° C., followed by benzyl bromide (292 mL, 2.42 mol, 1.2 eq) and the mixture was allowed stir at room temperature for 3 h. After completion of the reaction (monitored by TLC, 20% ethyl acetate-hexane, KMnO4, Rf=0.45), the reaction was quenched by adding ice cubes and the mixture was extracted with ethyl acetate (500 mL). The organic extract was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluting with 10% ethyl acetate in hexanes to afford 1 -benzyl-5-methylpyrrolidin-2-one in two fractions. The first fraction contained 200 g of 1 -benzyl-5-methylpyrrolidin-2- one (yield 52.4%, EC-MS: purity: 95%) and the second fraction contained an additional 100 g (yield 26%, EC-MS:purity: 83%) as an oily liquid. (ES): mlz 190.1 (M+H); tr=i.21, 1.61 mm.
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 3h; 1 Reaction step 1. Synthesis of 1-benzyl-5-methylpyrrolidin-2-one To a solution of 5-methylpyrrolidin-2-one (15 g, 152 mmol, 1.0 eq) in DMF (115 mL), was slowly added NaH (5.4 g, 230 mmol, 1.5 eq) followed by benzyl bromide (21.7 mL, 182 mmol, 1.2 eq) at 0 °C and the reaction mixture was allowed to warm to room temperature over 3h. After completion of reaction (monitored by TLC, 20% ethyl acetate-hexane, KMnO4, Rf = 0.45), the reaction was quenched by the addition of ice cubes and was extracted with ethyl acetate (500 mL). The organic extract was dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluting with 10% ethyl acetate in hexanes to afford 25 g of 1- benzyl-5-methylpyrrolidin-2-one as oil. LC-MS (ES+) m/z: 190.1 (M+1); purity = 92.5%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3h; Reaction step 1. Synthesis of 1-benzyl-5-methylpyrrolidin-2-one Reaction step 1. Synthesis of 1-benzyl-5-methylpyrrolidin-2-oneTo a solution of 5-methylpyrrolidin-2-one (15 g, 152 mmol, 1.0 eq) in DMF (115 mL), was slowly added NaH (5.4 g, 230 mmol, 1.5 eq) followed by benzyl bromide (21.7 mL, 182 mmol, 1.2 eq) at 0 °C and the reaction mixture was allowed to warm to room temperature over 3h. After completion of reaction (monitored by TLC, 20% ethyl acetate-hexane, KMnO4, Rf = 0.45), the reaction was quenched by the addition of ice cubes and was extracted with ethyl acetate (500 mL). The organic extract was dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluting with 10% ethyl acetate in hexanes to afford 25 g of 1-benzyl- 5-methylpyrrolidin-2-one as oil. LC-MS (ES+) m/z: 190.1 (M+1); purity = 92.5%
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3h; 1 Synthesis of 1-benzyl-5-methylpyrrolidin-3-yl)methyl 4-methylbenzenesulfonate To a solution of 5-methylpyrrolidin-2-one (15 g, 152 mmol, 1.0 eq) in DMF (115 mL), was slowly added NaH (5.4 g, 230 mmol, 1.5 eq) followed by benzyl bromide (21.7 mL, 182 mmol, 1.2 eq) at 0° C. and the reaction mixture was allowed to warm to room temperature over 3 hr. After completion of reaction (monitored by TLC, 20% ethyl acetate-hexane, KMnO4, Rf=0.45), the reaction was quenched by the addition of ice cubes and was extracted with ethyl acetate (500 mL). The organic extract was dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluting with 10% ethyl acetate in hexanes to afford 25 g of 1-benzyl-5-methylpyrrolidin-2-one as oil. LC-MS (ES+) m/z: 190.1 (M+1); purity=92.5%.
300 g With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; 1 Synthesis of 1-benzyl-5-methylpyrrolidin-2-one Step 1 Synthesis of 1-benzyl-5-methylpyrrolidin-2-one To a stirred solution of 5-methylpyrrolidin-2-one (200 g, 2.02 mol, 1.0 eq) in DMF (1.5 L), sodium hydride (60% suspension on mineral oil, 131 g, 3.03 mol, 1.5 eq) was slowly added at 0° C., followed by benzyl bromide (292 mL, 2.42 mol, 1.2 eq) and the mixture was allowed stir at room temperature for 3 h. After completion of the reaction (monitored by TLC, 20% ethyl acetate-hexane, KMnO4, Rf=0.45), the reaction was quenched by adding ice cubes and the mixture was extracted with ethyl acetate (500 mL). The organic extract was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluting with 10% ethyl acetate in hexanes to afford 1-benzyl-5-methylpyrrolidin-2-one in two fractions. The first fraction contained 200 g of 1-benzyl-5-methylpyrrolidin-2-one (yield 52.4%, LC-MS: purity: 95%) and the second fraction contained an additional 100 g (yield 26%, LC-MS: purity: 83%) as an oily liquid. (ES+): m/z 190.1 (M+H+); tr=1.21, 1.61 min.

  • 23
  • [ 108-27-0 ]
  • [ 626-01-7 ]
  • [ 1033693-04-7 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; caesium carbonate In 1,4-dioxane at 100℃; 1-(3-Aminophenyl)-5-methylpyrrolidin-2-one (cf. Scheme 17); A mixture of 10.1 g (100 mmol) of 5-methylpyrrolidin-2-one, 15 g (67 mmol) of 3-iodoaniline, 2.56 g (13.4 mmol) of copper(I) iodide, 0.25 g (26 mmol) of N,N'-dimethylenethyldiamine and 43.7 g (134 mmol) of caesium carbonate is taken up in 180 ml of dioxane and stirred at 100° C. overnight. After cooling, the reaction mixture is filtered through a silica gel cartridge, the cartridge is washed with ethyl acetate and the filtrate is concentrated under reduced pressure. The crude product is purified by column chromatography on silica gel (cyclohexane/ethyl acetate). This gives 7.5 g of the desired product (log P (pH 2.3): 0.52). 1H NMR (400 MHz, DMSO-d) δ=6.99 (t, 1H), 6.67 (t, 1H), 6.56-6.48 (m, 1H), 6.43-6.37 (m, 1H), 4.94 (s, 2H), 4.24-4.15 (m, 1H), 2.50-2.00 (m, 3H), 1.70-1.55 (m, 1H), 1.12 (d, 3H)
  • 24
  • [ 108-27-0 ]
  • [ 623-00-7 ]
  • [ 1352448-48-6 ]
YieldReaction ConditionsOperation in experiment
99% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;
  • 25
  • [ 108-27-0 ]
  • [ 619-42-1 ]
  • [ 1352448-46-4 ]
YieldReaction ConditionsOperation in experiment
91% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;
  • 26
  • [ 108-27-0 ]
  • [ 402-43-7 ]
  • [ 1352448-47-5 ]
YieldReaction ConditionsOperation in experiment
99% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;
  • 27
  • [ 108-27-0 ]
  • [ 139102-34-4 ]
  • [ 1352448-49-7 ]
  • 28
  • [ 108-27-0 ]
  • [ 586-78-7 ]
  • [ 13691-23-1 ]
YieldReaction ConditionsOperation in experiment
99% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; Inert atmosphere;
  • 29
  • [ 108-27-0 ]
  • [ 17229-17-3 ]
  • [ 1374247-37-6 ]
YieldReaction ConditionsOperation in experiment
2.15 g With tetrabutylammomium bromide; potassium hydroxide In tetrahydrofuran for 2.5h; Inert atmosphere; Reflux;
  • 30
  • [ 108-27-0 ]
  • [ 42016-93-3 ]
  • (2-chloro-4-iodo-phenyl)-(5-methyl-4,5-dihydro-3H-pyrrol-2-yl)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% Stage #1: 5-methylpyrrolidin-2-one; 2-chloro-4-iodoaniline With trichlorophosphate In 1,2-dichloro-ethane at 60℃; for 4h; Inert atmosphere; Stage #2: With potassium carbonate In water; 1,2-dichloro-ethane at 20℃; 5.2.6. (2-Chloro-phenyl)-(5-methyl-4,5-dihydro-3H-pyrrol-2-yl)-amine (10·HCl) General procedure: To a solution of 5-methyl-2-pyrrolidinone (1.71 g, 17.27 mmol) and 2-chloro-aniline 8 (2.2 g, 17.26 mmol) in 1,2-dichloroethane (35 mL) was added POCl3 (2.65 g, 17.27 mmol). The mixture was stirred at 60 °C for 4 h under a nitrogen atmosphere. After cooling to room temperature, H2O (30 mL) was added and the mixture was made basic by addition of saturated aqueous K2CO3. This solution was extracted with CH2Cl2 (3 × 50 mL) and the organic layer was washed, dried and evaporated. The residual oil was purified by column chromatography on silica gel using 5% Et3N in EtOAc as eluant and then crystallized from cyclohexane to give compound 10 (2.28 g, 65%) as a white solid: mp 92-93 °C. The hydrochloride salt, obtained by treatment with ethanolic HCl, was crystallized from 2-PrOH-Et2O:
  • 31
  • [ 108-27-0 ]
  • [ 95-51-2 ]
  • [ 1393348-67-8 ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: 5-methylpyrrolidin-2-one; o-chloroaniline With trichlorophosphate In 1,2-dichloro-ethane at 60℃; for 4h; Inert atmosphere; Stage #2: With potassium carbonate In water; 1,2-dichloro-ethane at 20℃; 5.2.6. (2-Chloro-phenyl)-(5-methyl-4,5-dihydro-3H-pyrrol-2-yl)-amine (10·HCl) To a solution of 5-methyl-2-pyrrolidinone (1.71 g, 17.27 mmol) and 2-chloro-aniline 8 (2.2 g, 17.26 mmol) in 1,2-dichloroethane (35 mL) was added POCl3 (2.65 g, 17.27 mmol). The mixture was stirred at 60 °C for 4 h under a nitrogen atmosphere. After cooling to room temperature, H2O (30 mL) was added and the mixture was made basic by addition of saturated aqueous K2CO3. This solution was extracted with CH2Cl2 (3 × 50 mL) and the organic layer was washed, dried and evaporated. The residual oil was purified by column chromatography on silica gel using 5% Et3N in EtOAc as eluant and then crystallized from cyclohexane to give compound 10 (2.28 g, 65%) as a white solid: mp 92-93 °C. The hydrochloride salt, obtained by treatment with ethanolic HCl, was crystallized from 2-PrOH-Et2O:
  • 32
  • [ 108-27-0 ]
  • [ 1809-20-7 ]
  • [ 1417780-50-7 ]
YieldReaction ConditionsOperation in experiment
75% With copper diacetate; potassium carbonate In toluene at 80℃; for 0.666667h; Molecular sieve;
  • 33
  • [ 5460-29-7 ]
  • [ 108-27-0 ]
  • 2-[3-(3-methyl-2-oxo-pyrrolidin-1-yl)-propyl]-isoindole-1,3-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
41% With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 25℃; for 16.5h; 8.1 STEP 1To an ice-cold solution of NaH (0.505 g, 12.6 mmol) in DMF (20 mL) 5-methyl-pyrrolidin-2-one (1.0 g, 10.1 mmol) in DMF (10.0 mL) was added slowly. This was stirred for 30 min at 0-25°C. 2-(3-Bromo-propyl)-isoindole-1 ,3-dione (2.47 g, 9.0 mmol) was added and the reaction was stin'ed at room temperature for 16 h. A solution of saturated NH CI (10.0 mL) was added and extracted with ethyl acetate. Organic layer was washed with LiCI solution and concentrated. The crude was purified on silica gel using CH2CI2/MeOH (10%) as eluent to give 2-[3-(3- methyl-2-oxo-pyrrolidin-1-yl)-propyl]-isoindole-1 ,3-dione (1.2 g, 41%).
  • 34
  • [ 1613-37-2 ]
  • [ 108-27-0 ]
  • 5-methyl-1-(quinolin-N-oxide-2-yl)pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With copper diacetate; silver carbonate In benzene at 110℃; for 24h; Sealed tube;
  • 35
  • [ 3764-01-0 ]
  • [ 108-27-0 ]
  • 1-(2,6-dichloropyrimidin-4-yl)-5-methylpyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% With sodium hydride In N,N-dimethyl-formamide at 20℃; Cooling with ice; 47; 48 In a lOOmL round-bottomed flask was added 2,4,6-trichloropyrimidine (1.03 g, 5.62 mmol) and 5-methyl-2-pyrrolidinone (0.58 g, 5.90 mmol) in DMF (12 mL) which was cooled with an icebath. NaH (95%, 0.204 g, 8.50 mmol) was added in 1 portion (bubbling occurred), and the reaction turned bright yellow. The reaction was stirred for 20 mm, and then the ice bath was removed. The reaction stirred overnight at room temperature. The reaction mixture was quenched slowly with water. The reaction mixture was poured into water and EtOAc. The phases were separated, and the aqueous layer extracted with EtOAc. The combined organiclayers were washed with diluted brine, dried over Na2SO4, filtered, and concentrated to abrown oil. The crude material was purified by silica gel chromatography (eluent 0-100%EtOAc/heptane) to give 1 -(2,6-dichloropyrimidin-4-yl)-5-methylpyrrolidin-2-one (245.9 mg, 18%yield) as an off white solid. LCMS: m/z 246.0 (M + H), Rt 0.87 mm. The enantiomers wereseparated via chiral HPLC on an AD column (20 mI/mm, 21 x 250 mm) eluting 95/5heptane/EtOH (v/v) to give (S)- 1 -(2,6-dichloropyrimidin-4-yl)-5-methylpyrrolidin-2-one and (R)1 -(2 ,6-dichloropyrimidin-4-yl)-5-methylpyrrol idi n-2-one.Peak 1: 81.9 mg. Retention time on analytical chiral column: 3.378 mm (8 mm run time).Peak 2: 73.1 mg. Retention time on analytical chiral column: 4.652 mm (8 mm run time).
  • 36
  • [ 333969-32-7 ]
  • [ 108-27-0 ]
  • 5-methyl-1-(1-(pyridin-2-yl)propyl)pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: 5-methylpyrrolidin-2-one With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.333333h; Inert atmosphere; Stage #2: 2-(1-bromopropyl)pyridine In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 3h; Inert atmosphere; General procedure: To an oven dried 25 mL round flask charged with stir bar under N2 atmosphere was added 1b (3.0 mmol, 1.0 equiv) followed by DMF(6.0 mL). The reaction flask was placed into a 0 C ice bath. To the solution under N2 was added NaH (3.9 mmol, 1.3 equiv, 60%dispersed in mineral oil). After 20 min, to the solution was added 2d (3.6 equiv, 1.2 equiv). The reaction flask was then removed fromthe ice bath and allowed to stir at ambient temperature for1.0-15.0 h. Reaction aliquot samples were taken for LCMS analysisto monitor the reaction to completion. The reaction mixture was slowly poured into a saturated aqueous NH4Cl solution (5 mL) under N2, diluted with water (10 mL), and extracted with EtOAc(15 mL 2). The organic layers were combined, washed with water (10 mL), brine (5 mL), and dried over MgSO4. After the removal of the organic solvents under reduced pressure, the resulting residue was purified by flash chromatography on 24 g silica gelcolumn using 0-60% EtOAc/hexanes as eluent to provide the desired product 3d.
  • 37
  • [ 108-27-0 ]
  • 4-(2-cyclopropyl-4-iodo-1H-benzo [d]imidazol-6-yl)-3,5-dimethylisoxazole [ No CAS ]
  • 1-(2-cyclopropyl-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-5-methylpyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine In 1,4-dioxane at 140℃; for 0.666667h; Inert atmosphere; Microwave irradiation; 136 1-(2-Cyclopropyl-6-(3,5-dimethylisoxazol-4-yl)-1H-benzo[d]imidazol-4-yl)-5-methylpyrrolidin-2-one (1020-136) To a mixture of 4-(2-cyclopropyl-4-iodo-1H-benzo[d]imidazol-6-yl)-3,5-dimethylisoxazole (30 mg, 0.08 mmol) (Example 8, Step 4), 5-methylpyrrolidin-2-one (100 mg, 1.00 mmol), copper(I) iodide (15 mg, 0.08 mmol), cesium carbonate (163 mg, 0.50 mmol) in 1,4-dioxane (2 mL) under nitrogen was added N,N-dimethylethane-1,2-diamine (14 mg, 0.16 mmol). The reaction mixture in a microwave vial was purged with dry nitrogen, capped, heated to 140° C. in a microwave reactor for about 40 minutes. The mixture was cooled, diluted with ethyl acetate (10 mL), filtered through a layer of celite, then partitioned between water and ethyl acetate, the aqueous phase was extracted with ethyl acetate twice, and the combined organic phase was washed with 1M aqueous K2CO3, 30% aqueous ammonium chloride, brine, dried and concentrated. The crude product was purified by reverse phase HPLC eluting with 0.1% TFA-containing acetonitrile/water to afford the title compound. C20H22N4O2. 351.2 (M+1). 1H NMR (DMSO-d6) δ 7.54 (s, 1H), 7.32 (s, 1H), 4.55 (m, 1H), 2.59 (m, 2H), 2.40-2.51 (m, 6H), 2.28 (s, 3H), 1.83 (m, 1H), 1.39 (m, 4H), 1.14 (d, J=6.2 Hz, 3H)
  • 38
  • [ 108-27-0 ]
  • [ 32202-61-2 ]
  • N-(2,3-dihydro-1H-inden-4-yl)-5-methylpyrrolidin-2-imine hydrochloride [ No CAS ]
  • 39
  • [ 108-27-0 ]
  • [ 452-84-6 ]
  • N-(2-fluoro-5-methylphenyl)-5-methylpyrrolidin-2-imine hydrochloride [ No CAS ]
  • 40
  • [ 108-27-0 ]
  • [ 95-81-8 ]
  • N-(2-chloro-5-methylphenyl)-5-methylpyrrolidin-2-imine hydrochloride [ No CAS ]
  • 41
  • [ 15854-87-2 ]
  • [ 108-27-0 ]
  • 5-methyl-1-(pyridin-4-yl)pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With copper(l) iodide; (R,R)-N,N'-dimethyl-1,2-diaminocyclohexane; potassium carbonate In 1,4-dioxane at 150℃; Sealed tube; Inert atmosphere; A mixture of 5-methylpyrrolidin-2-one (0.050 g, 0.50 mmcl), 4-iodopyridine (0.103 g, 0.50mmol), (trans)-N,N’-dimethylcyclohexane-1,2-diamine (0.016 mL, 0.10 mmcl), Cul (0.019 g,0.10 mmol) and K2C03 (0.209 g, 1.5 mmcl) in dioxane (2 mL) was sealed in a nitrogen flushedglass tube and heated with stirring at 150 °C overnight. The cooled reaction mixture wasconcentrated onto flash silica (5 mL). The resulting powder was purified by columnchromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 lm, 60 A], 30 mL per mm, 0 to 5% Solvent A in DCM, where Solvent A is 10% of (7 M NH3MeOH) in MeOH) to give 5-methyl-1-(pyridmn-4-yl)pyrrolidin-2-one (0.088 g, 99%) as an oil.LCMS (Method C): m/z 177 (M+H) (ES’), at 0.69 mm, UVactive
  • 42
  • [ 29266-73-7 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
64% With palladium 10% on activated carbon; hydrogen; sodium carbonate In ethanol for 16h; 48 Preparation 48: (R)-5-methylpyrrolidin-2-one (S)-5-(Iodomethyl)pyrrolidin-2-one (2.0 g, 8.9 mmol, 1.0 equiv.) was dissolved in ethanol (60 mL), sodium carbonate (1.036 g, 9.8 mmol, 1.1 equiv.) and 10% palladium on carbon (0.4 g) were added, and the mixture stirred for 16 hrs under a hydrogen atmosphere. The mixture was filtered through Celite and the filtrate concentrated under reduced pressure to afford an orange semi-solid. To the obtained residue was added 5% aqueous sodium thiosulfate, and the mixture extracted with ethyl acetate. The organic layer was dried (anhydrous sodium sulfate), filtered and concentrated in vacuo to give the title compound as a pale yellow oil (0.564 g, 64%). 1H NMR (300 MHz, CDCl3): δ 6.61 (br s, 1H), 3.82-3.72 (sext, 1H, J=6.6 Hz), 2.45-2.22 (m, 3H), 1.71-1.59 (m, 1H), 1.23-1.21 (d, 3H, J=6.6 Hz).
  • 43
  • [ 108-27-0 ]
  • [ 1221232-29-6 ]
  • 1-(4-chloroisoquinolin-6-yl)-5-methylpyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 100℃; for 3h; Inert atmosphere; 12.1 12.11 -(4-chloroisoquinolin-6-yl)-5-methylpyrroli- din-2-one 12.1 1-(4-chloroisoquinolin-6-yl)-5-methylpyrrolidin-2-one Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen were placed 6-bromo-4-chloroisoquinoline (161 mg, 0.66 mmol), 5-methylpyrrolidin-2-one (81.0 mg, 0.82 mmol), potassium phosphate (394 mg, 1.86 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform complex (32.1 mg, 0.03 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 35.7 mg, 0.06 mmol) and toluene (15 mL). The mixture was stirred for 3 h at 100° C. The reaction mixture was concentrated to dryness, redissolved in 20 mL of dichloromethane and washed with water (10 mL) and brine (10 mL). The organic phase was dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by silica gel chromatography (petrol ether/ethyl acetate). This resulted in 165 mg (73%) of the title compound as a light yellow solid.
  • 44
  • [ 108-27-0 ]
  • [ 106-45-6 ]
  • 5-methyl-N-(p-tolylthio)-2-pyrrolidone [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% With potassium fluoride; oxygen In 1,3,5-trimethyl-benzene at 100℃; for 1h; Autoclave; Catalytic reaction General procedure: The catalytic reaction was typically carried out according to the following procedure. Into a Pyrex glass reactor (volume: ca. 20 mL) were successively placed Cu(OH)x/Al2O3(Cu: 2 mol%), potassium fluoride (1 mmol), p-toluenethiol (1a, 0.5 mmol), 2-pyrrolidone (2a, 2 mmol), naphthalene (0.1 mmol, internal standard), mesitylene (2 mL), and a Teflon-coated magnetic stir bar, and then the mixture was stirred at 100 °C under O2 (1 atm). The conversions and product yields were determined by GC analysis using naphthalene as an internal standard. As forisolation of products, an internal standard was not added. After the reaction, the catalyst wasr emoved by simple filtration, and then the filtrate was concentrated by evaporation of mesitylene.The crude product was subjected to column chromatography on silica gel (typically usinghexane/ethyl acetate as an eluent), giving the pure N-acylsulfenamide. The products were identified by GC-MS and NMR (1H and 13C) analyses (see below).
  • 45
  • [ 108-27-0 ]
  • [ 67567-26-4 ]
  • (Z)-N-(4-bromo-2,6-difluorophenyl)-5-methylpyrrolidin-2-imine [ No CAS ]
YieldReaction ConditionsOperation in experiment
43% With triethylamine; trichlorophosphate In toluene for 3h; Reflux; 2.1 Step 1: (Z) -N- (4-Bromo-2,6-difluorophenyl) -5-methylpyrrolidin-2-imine 4-bromo-2,6-difluorobenzene (5 g, 24 mmol), 5-methylpyrrolidin-2-one (4.8 g, 48 mol) was added to the reaction flask, Triethylamine (7.2 g, 72 mmol), phosphorus oxychloride (11 g, 72 mmol) and toluene (50 mL) The reaction was stirred at reflux for 3 hours. Cooled to room temperature, concentrated under reduced pressure, dichloromethane (100 mL) was added, Saturated aqueous sodium carbonate solution (50 mL x 2) .The organic layer was dried over anhydrous sodium sulfate, The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel column chromatography (DCM / MeOH = 50/1) To give the title compound (3 g, yellow solid) in 43% yield.
  • 46
  • [ 108-27-0 ]
  • 3-ethyl-6-(hydroxymethyl)-5-methyl-1-(3,3,3-trifluoropropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione [ No CAS ]
  • 3-ethyl-5-methyl-6-[(2-methyl-5-oxopyrrolidin-1-yl)methyl]-1-(3,3,3-trifluoropropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
10% Stage #1: 3-ethyl-6-(hydroxymethyl)-5-methyl-1-(3,3,3-trifluoropropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione With thionyl chloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.333333h; Stage #2: 5-methylpyrrolidin-2-one With thionyl chloride; sodium hydride In tetrahydrofuran; dichloromethane; mineral oil at 20 - 60℃; for 108h; 10 3-Ethyl-5-methyl-6-[(2-oxoazetidin-1-yl)methyl]-1-(3,3,3-trifluoropropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione General procedure: Example 2 3-Ethyl-5-methyl-6-[(2-oxoazetidin-1-yl)methyl]-1-(3,3,3-trifluoropropyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione To a solution of 85 mg (1.19 mmol) of 2-azetidinone in 1.6 ml of THF were added 48 mg (1.19 mmol) of sodium hydride (60% suspension in mineral oil), then the mixture was heated to 60° C. for 60 min and subsequently cooled back down to RT ("Solution 1"). To a solution of 80 mg (0.238 mmol) of the compound from Ex. 140A in 1.6 ml of dichloromethane in another reaction vessel were added, at 0° C., 83 μl (0.476 mmol) of N,N-diisopropylethylamine and 18 μl (0.250 mmol) of thionyl chloride. After 20 min at 0° C., Solution 1 was added and the cooling bath was removed. The reaction mixture was stirred at RT for about 18 h. All the volatile constituents were then removed on a rotary evaporator. The remaining residue was separated into its components by means of preparative HPLC (Method 10). After concentration of the product fractions and drying under high vacuum, 5 mg (5% of theory, 92% purity) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6, δ/ppm): 4.69 (d, 1H), 4.29 (d, 1H), 4.08 (td, 2H), 3.90 (q, 2H), 3.59-3.52 (m, 1H), 2.84-2.68 (m, 2H), 2.42 (s, 3H), 2.39-2.28 (m, 1H), 2.27-2.16 (m, 1H), 2.15-2.03 (m, 1H), 1.59-1.44 (m, 1H), 1.16 (d, 3H), 1.11 (t, 3H). LC/MS (Method 1, ESIpos): Rt=0.97 min, m/z=418 [M+H]+.
  • 47
  • [ 60971-83-7 ]
  • [ 108-27-0 ]
  • C15H21N5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% Stage #1: 5-methylpyrrolidin-2-one With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #2: 1-(3-iodopropyl)-3,7-dimethyl-2,3,6,7-tetrahydro-1H-2,6-purinedione In N,N-dimethyl-formamide at 0 - 20℃; for 12h; 4 3,7-Dimethyl-1-(3-(2-oxooxazolidin-3-yl)propyl)-1H-purine-2,6(3H,7H)-dione Sodium hydride (27.6 mg, 0.690 mmol) was added to a solution of oxazolidin-2-one (68.3 mg, 0.690 mmol) in N,N-dimethylformamide (1 mL) at 0°C. The reaction solution was stirred at 20°C for 1 hour. A solution of 1-(3-iodopropyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione in N,N-dimethylformamide (1 mL) was added dropwise to the reaction solution at 0°C. The reaction solution was stirred at 20°C for 12 hours and then cooled to 0°C. The reaction was quenched by addition of saturated ammonium chloride solution (10 mL) and extracted with ethyl acetate (10 mL x 3). The organic phases were combined and washed with brine (10 mL x 3), dried over anhydrous sodium sulfate and concentrated under reduced pressure. 3,7-Dimethyl-1-(3-(2-oxooxazolidin-3-yl)propyl)-1H-purine-2,6(3H,7H)-dione (50.0 mg) was obtained after purification by preparative HPLC with a yield of 27%. 1H NMR: (400MHz, Methanol-d4) δ 7.85(s, 1H), 3.95(s, 3H), 3.92(s, 3H), 3.61-3.57(m, 2H), 3.09-3.08(m, 2H), 2.40-2.34(m, 2H), 2.28-2.25(m, 2H), 1.87-1.78(m, 2H), 1.63-1.60(m, 1H), 1.24-1.23(m, 3H). MS-ESI calcd. [M + H]+ 320, found 320.
  • 48
  • [ 108-27-0 ]
  • C5H8ClN [ No CAS ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate In dichloromethane at 40℃; for 1h; 11.1; 160.1 Step 1: Example lib [0339] A mixture of Example 11a (10.0 g, 100.0 mmol) and POCl3 (32.0 g, 200.0 mmol) in DCM (50 mL) was stirred at 40°C for 1 hour. The mixture concentrated to give the crude desired product Example lib (21.6 g, crude yield >100%) as colorless oil, which was used in the next step without further purification.
  • 49
  • [ 108-27-0 ]
  • (S)-tert-butyl 3-((4-(2-((5-amino-2-methylnaphthalen-1-yl)oxy)pyridin-3-yl)pyrimidin-2-yl)amino)piperidine-1-carboxylate [ No CAS ]
  • (3S)-tert-butyl 3-((4-(2-((2-methyl-5-(2-methyl-5-oxopyrrolidin-1-yl)naphthalen-1-yl)oxy)pyridin-3-yl)pyrimidin-2-yl)amino)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; for 12h; Inert atmosphere; 237.1 Step 1: (3S)-tert-Butyl 3 -((4-(2-((2-methyl-5 -(2-methyl-5-oxopyrrolidin- 1- yl)naphthalen- 1 -yl)oxy)pyridin-3 -yl)pyrimidin-2-yl)amino)piperidine- 1 -carboxylate To a solution of tert-butyl (3S)-3- [[4- [2- [(5 -iodo-2-methyl- 1 -naphthyl)oxy]-3 - pyridyl]pyrimidin-2-yl]amino]piperidine-1-carboxylate (110 mg, 0.17 mmol) in 1,4-dioxane (2 mL) was added copper (I) iodide (3 mg, 0.02 mmol), potassium carbonate (65 mg, 0.47 mmol), 5-methyl-2-pyrrolidinone (31 mg, 0.31 mmol) and N, N’-dimethyl- 1 ,2-ethanediamine (2.77 mg, 0.03 mmol). The mixture was purged with N2 and stirred at 110 °C for 12 h. After cooling, the mixture was filtered, concentrated and dissolved in ethyl acetate (60 mL), and subsequently washed with H20 (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate and filtered and the filtrate was concentrated and purified by prep-TLC (50% ethyl acetate in petroleum ether, Rf= 0.1) to yield 80 mg (83% yield) of the title compound as a white solid. LCMS (ESI) [M+H]= 609.1.
  • 50
  • [ 108-27-0 ]
  • (1S,2S)-N-(6-bromo-8-chloro-3-isoquinolyl)-2-fluorocyclopropanecarboxamide [ No CAS ]
  • (1S,2S)-N-(8-chloro-6-(2-methyl-5-oxopyrrolidin-1-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 90℃; for 3h; Inert atmosphere; 66.1 Step 1: (1S,2S)-N-(8-chloro-6-(2-methyl-5-oxopyrrolidin-1-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide A mixture of 5-methyl-2-pyrrolidinone (87 mg, 0.88 mmol), (1S,2S)-N-(6-bromo-8-chloro-3-isoquinolyl)-2-fluoro-cyclopropanecarboxamide (250 mg, 0.73 mmol), Xantphos (43 mg, 0.07 mmol), Pd2(dba)3 (67 mg, 0.07 mmol), and K3PO4 (462 mg, 2.18 mmol) in 1,4-dioxane (10 mL) was heated at 90° C. for 3 h under Ar. The reaction was concentrated to dryness. The residue was purified by silica gel column chromatography (EA:PE=1:1 to EA: DCM=2:1) to give the title compound as a yellow solid (200 mg, 76% yeild). LCMS (ESI) [M+H]+=362.1
  • 51
  • [ 156682-52-9 ]
  • [ 108-27-0 ]
  • 1-(4-bromo-2,3-difluorophenyl)-5-methylpyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; for 6h; To a solution of racemic 5-methylpyrrolidin-2-one (1.0 g, 10 mmol) in 1,4-dioxane (10 mL) at rt, were added <strong>[156682-52-9]1,4-dibromo-2,3-difluorobenzene</strong> (3.3 g, 12 mmol), K3PO4 (4.3 g, 20 mmol) and N,N'-dimethylethylenediamine (0.18 g, 2.0 mmol). The reaction mixture was purged with nitrogen for 5 min and then charged with copper (I) iodide (0.19 g, 1.0 mmol). The reaction mixture was again purged with nitrogen for 3 min and heated at 80 C. for 6 h. The reaction mixture was cooled, filtered through a Celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography (pet. ether-EtOAc) to give Intermediate 34 (0.90 g, 3.1 mmol, 31% yield) as brown liquid. MS(ESI) m/z: 291.0 [M+H]+. 1H NMR (400 MHz, CDCl3) delta=7.38-7.01 (m, 1H), 6.99-6.96 (m, 1H), 4.24-4.20 (m, 1H), 2.62-2.51 (m, 2H), 2.50-2.38 (m, 1H), 1.81-1.76 (m, 1H), 1.17 (d, J=6.4 Hz, 3H).
  • 52
  • [ 123-76-2 ]
  • [ 57-13-6 ]
  • [ 108-27-0 ]
YieldReaction ConditionsOperation in experiment
90.9% With formic acid at 180℃; for 8h; Autoclave; 1-7; 12; 17-25; 30-32 Example 31 Take 0.05 mol of levulinic acid, 0.5 mol of formic acid, 0.25 mol of urea, 0.29g of ruthenium carbon/copper oxide catalyst was placed in an autoclave and mixed evenly. Sealing the reaction kettle, Heat to 180 ° C under magnetic stirring for 8 h. The reaction was cooled to room temperature and the catalyst was recovered by filtration. Qualitative and quantitative testing using GC-MS (Shimadzu) and GC (Agilent), The test results are listed in Table 1 with the serial number 31.
  • 53
  • [ 108-27-0 ]
  • [ 19099-54-8 ]
  • 5-methyl-N-(2-isopropylphenyl)-2-pyrrolidone [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With potassium phosphate; copper(l) iodide; diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; C13H12F3NO In dimethyl sulfoxide at 90℃; for 24h; Inert atmosphere; Molecular sieve;
  • 54
  • [ 108-27-0 ]
  • [ 2113-51-1 ]
  • 1-([1,1'-biphenyl]-2-yl)-5-methylpyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With potassium phosphate; copper(l) iodide; diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; C13H12F3NO In dimethyl sulfoxide at 90℃; for 24h; Inert atmosphere; Molecular sieve;
  • 55
  • [ 108-27-0 ]
  • [ 74-86-2 ]
  • [ 4854-35-7 ]
YieldReaction ConditionsOperation in experiment
52.7% With potassium hydroxide In neat (no solvent) at 150℃; for 2h; Autoclave;
  • 56
  • [ 108-27-0 ]
  • C5H11NO2*(x)ClH [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In water at 0 - 80℃; Inert atmosphere; 11.1 Step 1: Into a 250 mL round-bottom flask were added 10.0 g( 101 mmol) of 5-methylpyrrolidin-2- one and 100 mL of concentrated HCI at 0 °C. The mixture was stirred at 80 °C overnight under nitrogen atmosphere and concentrated. The residue was diluted with ACN to yield precipitates, which were collected by filtration and washed with ACN. The solid was dried under vacuum to afford compound 46A hydrochloride salt. LC-MS: m/e = 118 [M+H]+.
  • 57
  • [ 108-27-0 ]
  • [ 96-32-2 ]
  • [ 70821-47-5 ]
YieldReaction ConditionsOperation in experiment
56% Stage #1: 5-methylpyrrolidin-2-one With sodium hydride In tetrahydrofuran; mineral oil at 7℃; for 1h; Stage #2: bromoacetic acid methyl ester In tetrahydrofuran; mineral oil at 7 - 20℃; for 1.5h; INTERMEDIATE 101 methyl 2-(2-methyl-5-oxopyrrolidin-1-yl)acetate To an ice-cold solution of anhydrous THF (60 mL) was added sodium hydride (60 % in mineral oil, 2.22 g, 55.4 mmol, 1.1 eq) portionwise. To the grey slurry was added a solution of 5-methylpyrrolidin-2-one (5.00 g, 50.4 mmol, 1.0 eq) in dry THF (20 mL) dropwise over 10 min, keeping the temperature below 7 °C. After a further 5 min, additional THF (40 mL) was added and the reaction stirred for a further 45 min before addition of methyl bromoacetate (5.7 mL, 60.5 mmol, 1.2 eq) in THF (10 mL). The reaction was allowed to warm to rt and stirred for 1.5 h. The reaction was poured into NH4Cl aq. sat. solution (100 mL), extracted with EtOAc (3 × 80 mL), washed with water (2 x 100mL), aq. NH4Cl (2 x 100 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the title compound (4.81 g, 56 %) as a colourless oil. UPLC (Method A): 1.86 min, 66 %, [M+H]+ = 172.1.
  • 58
  • [ 86-98-6 ]
  • [ 108-27-0 ]
  • 1-(7-Chloro-quinolin-4-yl)-5-methyl-pyrrolidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane Inert atmosphere; Reflux; 1-3 Example 1 Preparation of compound of formula III At room temperature, the formula 4,7-dichloroquinoline (19.8g, 100.0mmol), 5-methyl-2-pyrrolidone (14.9g, 150.0mmol), 4,5-bisdiphenylphosphine-9,9 -Dimethylxanthene (578mg, 1.0mmol), palladium acetate (224 mg, 1.0mmol) and cesium carbonate (48.8g, 150.0mmol) are mixed in 1,4-dioxane (150ml) and replaced with nitrogen Three times, the temperature was raised to reflux and stirred under the protection of nitrogen.TLC detects that the raw materials are consumed, the reaction is stopped, and the temperature is lowered to room temperature.Add ethyl acetate (300ml) and water (300ml) to the system, stir for a while, separate the layers, extract the aqueous phase with ethyl acetate (150ml) again, and combine the organic phases.The organic phase was washed with water (200ml) and saturated sodium chloride (200ml) successively, and concentrated under reduced pressure to dryness to obtain a yellow viscous liquid.The obtained viscous liquid was recrystallized with dichloromethane (20ml) and n-hexane (40ml) to obtain 16.2g of a yellow solid with a yield of 62%, namely the compound of formula III.
  • 59
  • [ 591-50-4 ]
  • [ 108-27-0 ]
  • [ 6724-71-6 ]
YieldReaction ConditionsOperation in experiment
74% With copper carbonate hydroxide; Cs2CO3; Ethane-1,2-diamine In 2-methyltetrahydrofuran at 110℃; for 24h; Sealed tube; 4.2 General procedure for the preparationof N-arylamides 3 General procedure: The corresponding aryl halide (1, 3.00 mmol) and amide(2, 3.60 mmol) were dissolved in 2-MeTHF (6 mL) in a40-mL vial, then 1,2-ethylenediamine (EDA, 3.00 mmol),Cs2CO3(7.50 mmol) and malachite (50.0 mg, 13.0 mol%)were added to this solution. The vial was then sealed with astopper and the reaction was stirred for 24 h at 110 °C. Themixture was then filtered, then washed with EtOAc (60 mL).After evaporation of the filtrate, the residue was purifiedby flash column chromatography. An analytical sample wasrecrystallized from the solvent given below after the meltingpoint. Compounds 3a-g, 3i-l and 3o-an are known in theliterature, while compounds 3h,m,n are new.
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