Name: 181289-23-6|(S)-4-Isobutylpyrrolidin-2-one|97%
Brand: Ambeed
SKU: A223590
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1
(-)-(S)-5-methyl-3-[(3-phenyl-allyloxycarbonylamino)methyl]-hexanoic acid 3-phenyl-allyl ester [ No CAS ]
[ 181289-23-6 ]
[ 148553-50-8 ]

Yield	Reaction Conditions	Operation in experiment
6.0 g	With morpholine; triphenylphosphine In ethanol for 3h; Heating;

Reference： [1]Hamersak, Zdenko; Stipetic, Irena; Avdagic, Amir [Tetrahedron Asymmetry, 2007, vol. 18, # 12, p. 1481 - 1485]

2
[ 944163-24-0 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With lithium In tetrahydrofuran; ammonia at -78℃; for 1h;

Reference： [1]Rodríguez, Verónica; Quintero, Leticia; Sartillo-Piscil, Fernando [Tetrahedron Letters, 2007, vol. 48, # 24, p. 4305 - 4308]

3
[ 181289-23-6 ]
[ 148553-50-8 ]

Yield	Reaction Conditions	Operation in experiment
94.1%	With ethanol; sodium hydroxide at 40℃; for 5h; Green chemistry;	21 Example 21: Preparation of pregabalin 78 g of intermediate 3 ((S)-4-isobutylpyrrolidin-2-one) was dissolved in 300 mL of absolute ethanol. Add 660 mL of 1 mol/L sodium hydroxide solution. Reaction at 40 ° C for 5 hours, The liquid phase detection intermediate 3 is completely converted, Move the reaction to the ice bath, Slowly add 675 mL of 1 mol/L hydrochloric acid. Evaporate the ethanol under reduced pressure, The residue was dissolved in ethyl acetate. Wash the organic phase with saturated brine, The organic phase is concentrated, Get the crude product of Pregabalin, Add 200 mL of an 80 wt% aqueous solution of isopropanol to the crude solid. Stir the mixture to reflux, The solids are all dissolved, Slowly cool to 0 ~ 5 ° C, Insulation for 15h, suction filtration, filter cake drying under reduced pressure, 82.7 g of a white solid were obtained, the yield was 94.1%, the purity was 99.5%, and the ee value was 99.7%.
93.2%	With lipase from Rhizopus delemar; sodium carbonate In water at 35℃; for 5h; Enzymatic reaction;	1.3; 2.3; 3.3; 4.3; 5.3 Step 3: Step 3: 10 g of the compound (D) obtained in step 2 and 300 mL of water were added into a reaction flask, stirred and the temperature was raised to 35° C., the pH value of the system was adjusted to 10 with sodium carbonate solution (with a mass fraction of 10%), 2 g of Lipase from Rhizopus delemar (producer: Guangzhou LES Biological Technology Co., Ltd., purity 98%) was added. The temperature was kept and the reaction solution was stirred for 5 h, after reacting for 1 h, sodium carbonate solution was added every 1 h to maintain the pH value in the range of 9-10. After the reaction was completed, the biological enzyme was removed by filtration, the pH value of the filtrate was adjusted to 6.5-7.5 with hydrochloric acid, cooled to 5-10° C., filtered and dried to obtain 10.5 g of target compound (B) pregabalin with a yield of 93.2%, the product enantiomeric excess value e.e.: 99.22%, and the hydrogen nuclear magnetic resonance spectrum of the product was the same as FIG. 1.
88%	With hydrogenchloride In water at 100 - 106℃; for 10h;	1.2; 1.3; 2.2; 2.3; 3.2; 3.2 (2) Preparation of crude (S)-pregabalin: Mix 70g of (S)-4-isobutylpyrrolidone-2-one prepared in step (1) with 100g of concentrated hydrochloric acid, raise the temperature to 100-106°C and reflux for 10h, then add 50ml of water to dilute after cooling, 30 % Sodium hydroxide solution to adjust the pH value to 5.8-6.2, lower the temperature to 0 , stir for 2h, filter, and wash the filter cake to obtain 77.8g (S)-pregabalin crude product, yield 98.6%, HPLC purity 99.56% .(3) Preparation (S)-Pregabalin boutique:Mix 70g of crude (S)-pregabalin prepared in step (2) with 1000ml of 80% ethanol solution, add 5g of powdered activated carbon, warm to reflux, decolorize at 78-84°C under reflux for 0.5 hours, filter while hot, and filtrate Cool to -5-0°C, filter after 2 hours of incubation, wash the filter cake with 80% ethanol, and dry to constant weight at 60°C to obtain 60.2g (S)-pregabalin boutique with a recrystallization yield of 88% and HPLC purity of 99.92%. (c = 1.06, water), literature reports (c = 1.06, water).In the process of synthesizing and refining (R)-(-)-3-(carbamoylmethyl)-5-methylhexanoic acid as a raw material to obtain high-purity (S)-pregabalin products, the total yield is 83.6 %.

78%	With potassium hydroxide In methanol for 5h; Heating;
73%	Stage #1: (S)-4-isobutyl-pyrrolidin-2-one With hydrogenchloride; water for 15h; Reflux; Stage #2: With tributyl-amine In water at -10 - 5℃; for 5h;	5 Example- 5 Synthesis of pregabalin: Compound V (12.0 gm, 0.086 mol) was dissolved in 80 mL of 6N HCl and refluxed for15 hours, then cooled to room temperature. Water was removed under vacuum and resultant solid product was dissolved in a solution of isopropyl alcohol (50 mL) and water (25 mL). Tributyl amine (22.3 gm) was added to the above mixture and stirred at -10 to 5° C for 5 hours. Solid material formed filtered and dried to get pregabalin as a colourless solid with yield of 10 gm (73%) isolated. H1NMR (300 MHz, D2O) δ 3.07-3.09 (d, 2H), 2.51-2.54 (t, 2H), 2.28-2.34 (m, 1H), 1.66-1.73 (m, 1H), 1.28-1.33 (t, 2H), 0.92-0.97 (dd, 6H). C13NMR (75 MHz, D2O) δ 21.35, 21.98, 24.38, 30.89, 36.23, 40.18, 43.06, 176.71. Chemical HPLC purity: 99.7%, Chiral HPLC Purity: 99.99%.
73%	Stage #1: (S)-4-isobutyl-pyrrolidin-2-one With hydrogenchloride; water for 15h; Reflux; Stage #2: With tributyl-amine In water; isopropyl alcohol at -10 - 5℃; for 5h;	5 Synthesis of Pregabalin Example-5 Synthesis of Pregabalin Compound V (12.0 gm, 0.086 mol) was dissolved in 80 mL of 6N HCl and refluxed for 15 hours, then cooled to room temperature. Water was removed under vacuum and the resultant solid product was dissolved in a solution of isopropyl alcohol (50 mL) and water (25 mL). Tributyl amine (22.3 gm) was added to the above mixture and stirred at -10 to 5° C. for 5 hours. The solid material formed was filtered and dried to get pregabalin as a colourless solid with yield of 10 gm (73%) isolated. H1NMR (300 MHz, D2O) δ 3.07-3.09 (d, 2H), 2.51-2.54 (t, 2H), 2.28-2.34 (m, 1H), 1.66-1.73 (m, 1H), 1.28-1.33 (t, 2H), 0.92-0.97 (dd, 6H). C13NMR (75 MHz, D2O) δ 21.35, 21.98, 24.38, 30.89, 36.23, 40.18, 43.06, 176.71. Chemical HPLC purity: 99.7%, Chiral HPLC Purity: 99.99%.
	Stage #1: (S)-4-isobutyl-pyrrolidin-2-one With hydrogenchloride; water at 125℃; for 15h; Stage #2: With triethylamine In 2-methyl-propan-1-ol for 0.75h;	7 Example 7: Preparation of (S) Pregabalin from compound 19; 1Og of compound 19 is dissolved in 440 ml 6 N HCl, and the solution is warmed to 125°C for 15 hours. After cooling, the mixture is diluted with water, and extracted three times with dichloromethane, then the aqueous phase is evaporated. After drying under high vacuum, the (S)-Pregabalin hydrochloride is obtained as crystals. (S)-Pregabalin is EPO further resolved by dissolving (S)-Pregabalin hydrochloride in isobutanol, and then adding triethyl amine. The mixture is stirred for 45 minutes, and the product is filtered, washed with isobutanol.
	With hydrogenchloride; water

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A Location in patent: Paragraph 0102-0104
[2]Current Patent Assignee: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.; ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL - US2021/114972, 2021, A1 Location in patent: Paragraph 0045; 0048; 0051; 0054; 0057
[3]Current Patent Assignee: ZHEJIANG BAMBOO PHARMACY - CN110963934, 2020, A Location in patent: Paragraph 0041; 0045-0050; 0054-0059; 0063-0073
[4]Rodríguez, Verónica; Quintero, Leticia; Sartillo-Piscil, Fernando [Tetrahedron Letters, 2007, vol. 48, # 24, p. 4305 - 4308]
[5]Current Patent Assignee: DIVI S LAB; DIVI'S LABORATORIES LIMITED - EP2418194, 2012, A1 Location in patent: Page/Page column 10
[6]Current Patent Assignee: DIVI S LAB; DIVI'S LABORATORIES LIMITED - US2012/41212, 2012, A1 Location in patent: Page/Page column 7
[7]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2006/110783, 2006, A2 Location in patent: Page/Page column 14-15
[8]Li, Xiuxiu; You, Cai; Yang, Yusheng; Yang, Yuhong; Li, Pan; Gu, Guoxian; Chung, Lung Wa; Lv, Hui; Zhang, Xumu [Chemical Science, 2018, vol. 9, # 7, p. 1919 - 1924]

4
C₁₄H₂₁N [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 90 percent / DMAP / tetrahydrofuran / 2 h / 20 °C 2: 68 percent / Et₃B; nBu₃SnH; O₂ / BF₃*OEt₂ / tetrahydrofuran / -78 °C 3: 88 percent / Li / liquid ammonia; tetrahydrofuran / 1 h / -78 °C

Reference： [1]Rodríguez, Verónica; Quintero, Leticia; Sartillo-Piscil, Fernando [Tetrahedron Letters, 2007, vol. 48, # 24, p. 4305 - 4308]

5
[ 1019107-67-5 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 68 percent / Et₃B; nBu₃SnH; O₂ / BF₃*OEt₂ / tetrahydrofuran / -78 °C 2: 88 percent / Li / liquid ammonia; tetrahydrofuran / 1 h / -78 °C

Reference： [1]Rodríguez, Verónica; Quintero, Leticia; Sartillo-Piscil, Fernando [Tetrahedron Letters, 2007, vol. 48, # 24, p. 4305 - 4308]

6
[ 949890-69-1 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: triethylamine; diphenylphosphoryl azide / toluene / 20 - 90 °C 1.2: toluene / Heating 2.1: morpholine; triphenylphosphine / Pd(OAc)2 / ethanol / 3 h / Heating

Reference： [1]Hamersak, Zdenko; Stipetic, Irena; Avdagic, Amir [Tetrahedron Asymmetry, 2007, vol. 18, # 12, p. 1481 - 1485]

7
[ 185815-59-2 ]
[ 181289-23-6 ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1481 - 1485

8
4-isobutyl-2-oxopyrrolidine-3-carboxylic acid [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	In toluene at 140℃; for 6h;	6 Example 6: Preparation of (S) 4-isobutylpyrrolidin-2-one, compound 19; 135 ml of 1 N NaOH is added to a solution of 24 g of compound 18 in 350 ml of ethanol at room temperature. After 30 minutes of stirring at that temperature, the reaction mixture is concentrated in vacuo. Then, 250 ml of 6 N HCl in water are added to the residue, and the phases are separated. The aqueous phase is extracted with 120 ML OF CH2Cl2, and then the combined organic layers are dried over MgSO4, filtered, and evaporated under reduced pressure to provide the corresponding carboxylic acid (compound 18, wherein R2 is H). A solution of the carboxylic acid in 120 ml of toluene refluxed at 14O0C for 6 hours, and then the mixture is concentrated under reduced pressure to dryness. The crude compound 19 is purified by column chromatography on silica gel to give desired pure compound 19.
1.71 g	In toluene for 6h; Reflux;	4.3.4. (S)-4-Isobutylpyrrolidin-2-one (6)¹¹ NaOH (1 N, 20 mL) was added to the solution of 5 (2.87 g, 13.5 mmol) in EtOH (60 mL) at room temperature. After stirring for 30 min, the reaction mixture was concentrated in vacuo. To the residue was added H2O and 5 N HCl, and the aqueous phase was extracted with CHCl3 (3×50 mL). The extract was dried over MgSO4, filtrated, and concentrated in vacuo to afford the corresponding carboxylic acid, which was used without further purification. After refluxing in toluene (30 mL) for 6 h, the reaction mixture was purified by column chromatography on silica gel (ethyl acetate/petroleum ether=1:6 as eluent) to afford desired product 6 (1.71 g, 90%). Colorless oil; 98% ee; 1H NMR (400 MHz, CDCl3): δ 6.30 (s, 1H), 3.48 (dd, J=8.8 Hz, 1H), 2.99 (dd, J=7.2, 2.4 Hz, 1H), 2.50-2.58 (m, 1H), 2.42 (dd, J=8.8, 8 Hz, 1H), 1.97 (dd, J=8.8, 8 Hz, 1H), 1.53-1.61 (m, 1H), 1.31-1.37 (m, 2H), 0.89-0.92 (m, 6H); 13C NMR (100 MHz, CDCl3): δ 178.8, 48.3, 43.8, 37.1, 32.8, 26.1, 22.6, 22.4; Chiral HPLC (Daicel Chiralpak AD-H) hexanes/2-propanol=96:4; flow rate: 1.0 mL/min; λ=210 nm; tmajor=12.8 min, tminor=14.6 min.

Reference： [1]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - WO2006/110783, 2006, A2 Location in patent: Page/Page column 14
[2]Location in patent: experimental part Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]

9
[ 181289-23-6 ]
[ 148553-50-8 ]
(R)-pregabalin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60 % ee	With hydrogenchloride In water for 12h; Heating / reflux; Acidic aqueous solution;	9 (4S)-(+)-Isobutylpyrrolidin-2-one (VII), prepared as in Example 8 (1.0 g, 7.1 mmol) was dissolved in 10 mL of 6N HCl and heated to reflux for 12 hours, then cooled to room temperature. The pH was adjusted to 7 by addition of IN NaOH, the solid was filtered, washed with H2O and dried, yielding the title product (1.0 g). HPLC analysis after derivatization with Marfey's reagent and isocratic elution with 0.05M triethylamine (adjusted to pH 3 with phosphoric acid)/acetonitrile on a Spheri-5 RP-18 cartridge column and a wavelength of 340 nm showed 60% enantiomeric excess of Pregabalin.

Reference： [1]Current Patent Assignee: GRUPO INSUD - WO2009/53446, 2009, A2 Location in patent: Page/Page column 31

10
[ 1144854-32-9 ]
[ 1144854-31-8 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With methanesulfonic acid In toluene for 14h; Heating / reflux;	8 A 50-mL round bottomed flask fitted with a reflux condenser was loaded with 4-isobutyl- l-((lR)-phenylethyl)-pyrrolidin-2-one (Via) (78:22 diastereoisomeric mixture) (2.0 g, 8.1 mmol), prepared as in Example 7, methanesulfonic acid (4.0 g, 41.6 mmol) and toluene (5 mL). The mixture was vigorously stirred and heated at reflux for 14 hours. The progress of the reaction was monitored by TLC eluting with ethyl acetate and staining with KMn(V After complete deprotection the mixture was cooled and carefully quenched into aqueous bicarbonate and extracted into ethyl acetate after pH adjustment to 8-9 . The organic layer was washed twice with water, brine and concentrated to residue under reduced pressure. The resulting oil was purified by silica gel chromatography eluting with ethyl acetate, yielding the title compound (VII) (1.10 g) as a colourless oil.Yield: 96%.H NMR and C NMR spectra were identical to those of the racemic material reported above (Example 6)[GC]D=+ 1 .6° (C=2.77, MeOH)For comparison an analytical sample of (4S)-(+)-Isobutylpyrrolidin-2-one was prepared from enantiomerically pure Pregabalin.[α]D=+2.4o (c=l .08, MeOH)

Reference： [1]Current Patent Assignee: GRUPO INSUD - WO2009/53446, 2009, A2 Location in patent: Page/Page column 30

11
[ 181289-23-6 ]
(+)-(3S)-3-(aminomethyl)-5-methylhexanoic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride; water at 100℃; for 10h;	4.3.5. (S)-3-Aminomethyl-5-methyl-hexanoic acid (Pregabalin) hydrochloride (1·HCl)^2a The product could also be obtained from 6: the solution of 6 (107 mg, 0.55 mmol) in 6 N HCl (2.7 mL) was refluxed at 100 °C for 10 h. The reaction mixture was concentrated in vacuo to afford hydrochloride of Pregabalin 1·HCl (129 mg, 95%). White solid; [α]D20 +7.15(c 1.1, H2O) (Ref. 2a [α]D20 +7.0(c 1.1, H2O)); 1H NMR (400 MHz, CD3OD): δ 2.96-2.98 (m, 1H), 2.37-2.48 (m, 1H), 2.18-2.24 (m, 1H), 1.66-1.73 (m, 1H), 1.25-1.29 (m, 1H), 0.92-0.96 (m, 6H); 13C NMR (CD3OD, 100 MHz): δ=175.7, 44.4, 41.9, 37.2,32.4, 26.0, 23.1, 22.6.
92%	With hydrogenchloride; water at 90℃; for 18h;	7.3 synthesis of pregabalin hydrochloride (S) -4- isobutyl-2-one (1.13g, 8.0mmol), added with 5M HCl (20mL), and reacted at 90°C 18 hours, cooled and ethyl acetate (4 × 50mL ) was extracted, the aqueous phase was concentrated to give pregabalin hydrochloride (1.17g, yield 92%).

Reference： [1]Location in patent: experimental part Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]
[2]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN104557583, 2016, B Location in patent: Paragraph 0074; 0084

12
ethyl 4-isobutyl-2-oxopyrrolidine-3-carboxylate [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: water; sodium hydroxide / ethanol / 0.5 h / 20 °C 2: toluene / 6 h / Reflux

Reference： [1]Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]

13
[ 34209-90-0 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1-{3,5-bis(trifluoromethyl)phenyl}-3-{(1R,2R)-2-(dimethylamino)cyclohexyl}thiourea / 24 h / -20 °C / Neat (no solvent) 2: hydrogen / tetrahydrofuran; ethanol / 24 h / 20 °C / 3040.2 Torr 3: water; sodium hydroxide / ethanol / 0.5 h / 20 °C 4: toluene / 6 h / Reflux

Reference： [1]Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]

14
[ 102014-44-8 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: dicyclohexyl-carbodiimide; copper(l) chloride / diethyl ether / 20 °C 1.2: 0 - 20 °C 2.1: 1-{3,5-bis(trifluoromethyl)phenyl}-3-{(1R,2R)-2-(dimethylamino)cyclohexyl}thiourea / 24 h / -20 °C / Neat (no solvent) 3.1: hydrogen / tetrahydrofuran; ethanol / 24 h / 20 °C / 3040.2 Torr 4.1: water; sodium hydroxide / ethanol / 0.5 h / 20 °C 5.1: toluene / 6 h / Reflux

Reference： [1]Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]

15
[ 590-86-3 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: sodium hydroxide / ethanol; water / 0 - 20 °C 2.1: dicyclohexyl-carbodiimide; copper(l) chloride / diethyl ether / 20 °C 2.2: 0 - 20 °C 3.1: 1-{3,5-bis(trifluoromethyl)phenyl}-3-{(1R,2R)-2-(dimethylamino)cyclohexyl}thiourea / 24 h / -20 °C / Neat (no solvent) 4.1: hydrogen / tetrahydrofuran; ethanol / 24 h / 20 °C / 3040.2 Torr 5.1: water; sodium hydroxide / ethanol / 0.5 h / 20 °C 6.1: toluene / 6 h / Reflux
	Multi-step reaction with 3 steps 1: potassium <i>tert</i>-butylate / tert-butyl methyl ether / 13 h / 25 °C / Green chemistry 2: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / toluene / 30 h / 25 °C / Green chemistry 3: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry
	Multi-step reaction with 3 steps 1: sodium methylate / methanol / 7 h / 25 °C / Green chemistry 2: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / water; cyclohexane / 12 h / 25 °C / Green chemistry 3: 5%-palladium/activated carbon; hydrogen / ethanol / 4 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry

	Multi-step reaction with 3 steps 1: caesium carbonate / toluene / 10 h / 50 °C / Green chemistry 2: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / ethanol / 30 h / 25 °C / Green chemistry 3: hydrogen; 5% Pd(OH)₂/C / methanol / 12 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry
	Multi-step reaction with 3 steps 1: sodium ethanolate / ethanol / 10 h / 25 °C / Green chemistry 2: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / toluene; water / 12 h / 25 °C / Green chemistry 3: 5%-palladium/activated carbon; hydrogen / ethanol / 4 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry

Reference： [1]Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]
[2]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A
[3]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A
[4]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A
[5]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A

16
[ 620960-36-3 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrogen / tetrahydrofuran; ethanol / 24 h / 20 °C / 3040.2 Torr 2: water; sodium hydroxide / ethanol / 0.5 h / 20 °C 3: toluene / 6 h / Reflux

Reference： [1]Liu, Jin-Ming; Wang, Xin; Ge, Ze-Mei; Sun, Qi; Cheng, Tie-Ming; Li, Run-Tao [Tetrahedron, 2011, vol. 67, # 3, p. 636 - 640]

17
[ 1101167-76-3 ]
[ 1272663-99-6 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydrogen In methanol for 12h;	4 Example - 4 Synthesis of (4S)-4-isobutylpyrrolidin-2-one V: To a mixture of compounds IVa and IVb (5 gm, 0.0352 mol) in methanol (100 mL), a 10% Palladium on carbon (0.5 gm) was added and stirred in a hydrogenation unit for about 12 hours. Palladium on carbon was removed by filtering under cellite, and solvent was evaporated under reduced pressure to obtain compound V as a low melting solid in 99% yield. H1NMR (300 MHz, CDCl3) δ 3.48-3.53 (dd, 1H), 3.02 (t, 1H), 2.37-2.57 (m, 2H), 1.97-2.02 (m, 1H), 1.53-1.60 (m, 1H), 1.33-1.38 (t, 2H), 0.9-0.92 (dd, 6H). C13NMR (75 MHz, CDCl3) δ 22.48, 22.67, 26.14, 32.93, 37.5, 43.86, 48.4, 179.0.
99%	With hydrogen In methanol for 12h;	4 Synthesis of (4S)-4-isobutylpyrrolidin-2-one V Example-4 Synthesis of (4S)-4-isobutylpyrrolidin-2-one V To a mixture of compounds IVa and IVb (5 gm, 0.0352 mol) in methanol (100 mL), a 10% Palladium on carbon (0.5 gm) was added and stirred in a hydrogenation unit for about 12 hours. Palladium on carbon was removed by filtering under cellite, and the solvent was evaporated under reduced pressure to obtain compound V as a low melting solid in 99% yield. H1NMR (300 MHz, CDCl3) δ 3.48-3.53 (dd, 1H), 3.02 (t, 1H), 2.37-2.57 (m, 2H), 1.97-2.02 (m, 1H), 1.53-1.60 (m, 1H), 1.33-1.38 (t, 2H), 0.9-0.92 (dd, 6H). C13NMR (75 MHz, CDCl3) δ 22.48, 22.67, 26.14, 32.93, 37.5, 43.86, 48.4, 179.0.

Reference： [1]Current Patent Assignee: DIVI S LAB; DIVI'S LABORATORIES LIMITED - EP2418194, 2012, A1 Location in patent: Page/Page column 10
[2]Current Patent Assignee: DIVI S LAB; DIVI'S LABORATORIES LIMITED - US2012/41212, 2012, A1 Location in patent: Page/Page column 7

18
[ 1374336-27-2 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With hydrogen; acetic acid; trifluoroacetic acid	1 For reduction step, pyrrolidinone (Illb, 19.5 g) was dissolved in acetic acid (150 ml) and after addition of 10% Pd-C (1 g) and trifluoroacetic acid (1 ml), the reaction mixture was under vigorous stirring hydrogenated under normal pressure until starting material disappeared. The slurry was filtered to remove the catalyst, the filtrate evaporated under reduced pressure to give 10.2 g (83% isolated yield) (S)-4-isobutyl-pyrrolidin-2-one (lib) with identical analytical data as reported in Helv. Chim. Acta 1999, 82, 2365 on page 2375 or in Tetrahedron Letters 2007, 48, 4305 or in Org. Proc. Res.&Develop. 1997, 1 , 26.The (S)-4-isobutyl-pyrrolidin-2-one was then hydrolyzed either with 4N-HCI to (S)- Pregabalin as reported in e.g. Synlett 2006, 10, 1589 or with aqueous KOH solution as given in Tetrahedron Letters 2007, 48, 4305.

Reference： [1]Current Patent Assignee: DRUG PROCESS LICENSING ASSOCIATES, LLC - WO2012/59830, 2012, A1 Location in patent: Page/Page column 13-14

19
[ 148553-50-8 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With acidic kaolin In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Reflux;	1-8 Example 7 Add 10 g of pregabalin to 100 mL of xylene and add 5 g of acidic kaolin.Then connect the water separator and heat the reflux reaction for 6 hours.The water produced during the reaction is separated in real time; after the reaction is finished, it is slowly cooled to room temperature.Filtration, removal of insoluble matter, and the obtained filtrate was evaporated to remove the solvent by a rotary evaporator.The obtained solid was further crystallized from ethyl acetate: cyclohexane (1:1).Target productS-preparin lactam8.60g, HPLC purity 99.3%,The yield was 97%.
	With diazomethyl-trimethyl-silane In methanol; hexane for 0.5h;	2 (S)-4-lsobutylpyrrolidin-2-one ((S)-13) (S)Pregabalin (50 mg, 0.3 mmol) was disolved in MeOH (5 mL) and TMS-diazomethane (900mL, 2 M solution in hexane) was added dropwise until the solution stayed yellow. Then the solution was stirred for 30 mm and the solvent was removed under vacuum to give a brown oil (50 mg). The products (not pure) were identified by GO-MS analysis.
	at 80℃; for 336h;	The cyclisation rate constants are detailed in Table 3 and show that decomposition of both drugs is significantly retarded through intercalation into LDHs, both at ambient and elevated temperatures. At 80 °C, decomposition of the pristine drugs in solution was significant over a two week period, whereas decomposition of the drugs within the intercalation compounds was only just measurable within experimental error, the cyclisation rate constant being reduced by a factor of 15.0 in the case of GBP, and 16.6 in the case of PGB. Similarly, at 20 °C measurable decomposition of the pristine drugs occurred within a four week period, whereas decomposition of the drugs within the nanohybrids was not sufficiently significant to be measurable.

	With diazomethyl-trimethyl-silane In methanol; hexane for 0.5h;
	Multi-step reaction with 2 steps 1: oxalyl dichloride / 18 h / -10 - 20 °C 2: acetonitrile / 6 h / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride / 10 h / -20 - 20 °C 2: tetrahydrofuran / 2 h / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride / 20 h / -10 - 20 °C 2: tetrahydrofuran / 2 h / Reflux

Reference： [1]Current Patent Assignee: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.; ZHEJIANG HUAHAI LICHENG PHARMACEUTICAL - CN109851543, 2019, A Location in patent: Paragraph 0022-0037
[2]Current Patent Assignee: NOVARTIS AG; Sandoz (in: Novartis) - WO2016/75082, 2016, A1 Location in patent: Page/Page column 102; 103
[3]Current Patent Assignee: UNIVERSITY OF OXFORD; Oxford University Innovation (in: Oxford University) - WO2017/89804, 2017, A1 Location in patent: Paragraph 00133-00135
[4]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]
[5]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A
[6]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A
[7]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A

20
[ 74611-85-1 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 9-O-allyl-6'-demethylquinidine / tetrahydrofuran / 24 h / 20 °C 2: hydrogen / ethanol / 18 h / 80 °C / 2280.15 Torr
	Multi-step reaction with 2 steps 1: 9-O-allyl-6'-demethylquinidine; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 24 h / 20 °C 2: hydrogen / ethanol / 18 h / 80 °C / 2280.15 Torr

Reference： [1]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN104557583, 2016, B
[2]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN104557583, 2016, B

21
[ 100401-40-9 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogen In ethanol at 80℃; for 18h;	7.2 in which the hydrogenation reaction vessel was added (R) -2- (4- nitro-methyl-pentyl) maleate (2.60g, 10.0mmol), Raney nickel (2.0mg) and ethanol ( 10 mL), purged with hydrogen three times, and three at 80 deg.] C under atmospheric pressure for 18 hours. The reaction mixture was then filtered through Celite and washed with ethanol to give (S) -4- isobutyl-2-one (1.27g, yield 90%).

Reference： [1]Current Patent Assignee: SUN YAT-SEN UNIVERSITY (CHINA) - CN104557583, 2016, B Location in patent: Paragraph 0074; 0080

22
0.333NO₃^(1-)*1.8Mg⁽²⁺⁾*Al⁽³⁺⁾*5.6HO^(1-)*0.667C₈H₁₆NO₂^(1-) [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	at 80℃; for 336h;	The cyclisation rate constants are detailed in Table 3 and show that decomposition of both drugs is significantly retarded through intercalation into LDHs, both at ambient and elevated temperatures. At 80 °C, decomposition of the pristine drugs in solution was significant over a two week period, whereas decomposition of the drugs within the intercalation compounds was only just measurable within experimental error, the cyclisation rate constant being reduced by a factor of 15.0 in the case of GBP, and 16.6 in the case of PGB. Similarly, at 20 °C measurable decomposition of the pristine drugs occurred within a four week period, whereas decomposition of the drugs within the nanohybrids was not sufficiently significant to be measurable.

Reference： [1]Current Patent Assignee: UNIVERSITY OF OXFORD; Oxford University Innovation (in: Oxford University) - WO2017/89804, 2017, A1 Location in patent: Paragraph 00133-00135

23
[ 1119-16-0 ]
[ 181289-23-6 ]
C₁₅H₂₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: dichloromethane / 27 h / Molecular sieve 2: toluene / 5 h / Reflux 3: water; sodium acetate; acetic acid / 1 h / 20 °C 4: pyridoxal 5'-phosphate; ammonium formate / aq. phosphate buffer; N,N-dimethyl-formamide / 24 h / pH 7 / Heating; Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

24
[ 1119-16-0 ]
[ 181289-23-6 ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: dichloromethane / 27 h / Molecular sieve 2: toluene / 5 h / Reflux 3: water; sodium acetate; acetic acid / 1 h / 20 °C 4: pyridoxal 5'-phosphate; Bacillus subtilis AlaDH; FDH; ammonium formate; D-Alanine; NAD / aq. phosphate buffer / 24 h / 30 °C / pH 7 / Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

25
[ 626-89-1 ]
[ 181289-23-6 ]
C₁₅H₂₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium acetate; pyridinium chlorochromate; aluminum oxide / dichloromethane / 4 h / 0 - 20 °C 2: dichloromethane / 27 h / Molecular sieve 3: toluene / 5 h / Reflux 4: water; sodium acetate; acetic acid / 1 h / 20 °C 5: pyridoxal 5'-phosphate; ammonium formate / aq. phosphate buffer; N,N-dimethyl-formamide / 24 h / pH 7 / Heating; Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

26
[ 626-89-1 ]
[ 181289-23-6 ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: sodium acetate; pyridinium chlorochromate; aluminum oxide / dichloromethane / 4 h / 0 - 20 °C 2: dichloromethane / 27 h / Molecular sieve 3: toluene / 5 h / Reflux 4: water; sodium acetate; acetic acid / 1 h / 20 °C 5: pyridoxal 5'-phosphate; Bacillus subtilis AlaDH; FDH; ammonium formate; D-Alanine; NAD / aq. phosphate buffer / 24 h / 30 °C / pH 7 / Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

27
[ 5362-56-1 ]
[ 181289-23-6 ]
C₁₅H₂₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: palladium 10% on activated carbon; hydrogen / toluene / 24 h / 20 °C 2: dichloromethane / 27 h / Molecular sieve 3: toluene / 5 h / Reflux 4: water; sodium acetate; acetic acid / 1 h / 20 °C 5: pyridoxal 5'-phosphate; ammonium formate / aq. phosphate buffer; N,N-dimethyl-formamide / 24 h / pH 7 / Heating; Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

28
[ 5362-56-1 ]
[ 181289-23-6 ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: palladium 10% on activated carbon; hydrogen / toluene / 24 h / 20 °C 2: dichloromethane / 27 h / Molecular sieve 3: toluene / 5 h / Reflux 4: water; sodium acetate; acetic acid / 1 h / 20 °C 5: pyridoxal 5'-phosphate; Bacillus subtilis AlaDH; FDH; ammonium formate; D-Alanine; NAD / aq. phosphate buffer / 24 h / 30 °C / pH 7 / Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

29
Diisobutyl-((E)-4-methyl-pent-1-enyl)-amine [ No CAS ]
[ 181289-23-6 ]
C₁₅H₂₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: toluene / 5 h / Reflux 2: water; sodium acetate; acetic acid / 1 h / 20 °C 3: pyridoxal 5'-phosphate; ammonium formate / aq. phosphate buffer; N,N-dimethyl-formamide / 24 h / pH 7 / Heating; Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

30
Diisobutyl-((E)-4-methyl-pent-1-enyl)-amine [ No CAS ]
[ 181289-23-6 ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: toluene / 5 h / Reflux 2: water; sodium acetate; acetic acid / 1 h / 20 °C 3: pyridoxal 5'-phosphate; Bacillus subtilis AlaDH; FDH; ammonium formate; D-Alanine; NAD / aq. phosphate buffer / 24 h / 30 °C / pH 7 / Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

31
C₂₀H₄₀NO₂⁽¹⁺⁾*Br^(1-) [ No CAS ]
[ 181289-23-6 ]
C₁₅H₂₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: water; sodium acetate; acetic acid / 1 h / 20 °C 2: pyridoxal 5'-phosphate; ammonium formate / aq. phosphate buffer; N,N-dimethyl-formamide / 24 h / pH 7 / Heating; Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

32
C₂₀H₄₀NO₂⁽¹⁺⁾*Br^(1-) [ No CAS ]
[ 181289-23-6 ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: water; sodium acetate; acetic acid / 1 h / 20 °C 2: pyridoxal 5'-phosphate; Bacillus subtilis AlaDH; FDH; ammonium formate; D-Alanine; NAD / aq. phosphate buffer / 24 h / 30 °C / pH 7 / Enzymatic reaction

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

33
tert-butyl 3-formyl-5-methylhexanoate [ No CAS ]
[ 181289-23-6 ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
80 % ee	Stage #1: tert-butyl 3-formyl-5-methylhexanoate With D-Alanine; FDH; pyridoxal 5'-phosphate; Bacillus subtilis AlaDH; NAD; ammonium formate In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; Stage #2: With water; sodium hydroxide enantioselective reaction;

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

34
tert-butyl 3-formyl-5-methylhexanoate [ No CAS ]
[ 75-31-0 ]
[ 181289-23-6 ]
C₁₅H₂₉NO₂ [ No CAS ]
C₂₄H₄₅NO₄ [ No CAS ]
[ 181289-22-5 ]

Yield	Reaction Conditions	Operation in experiment
76 % ee	Stage #1: tert-butyl 3-formyl-5-methylhexanoate; isopropylamine With pyridoxal 5'-phosphate; ammonium formate In aq. phosphate buffer; N,N-dimethyl-formamide for 24h; Heating; Enzymatic reaction; Stage #2: With water; sodium hydroxide enantioselective reaction;

Reference： [1]Fuchs, Christine S.; Farnberger, Judith E.; Steinkellner, Georg; Sattler, Johann H.; Pickl, Mathias; Simon, Robert C.; Zepeck, Ferdinand; Gruber, Karl; Kroutil, Wolfgang [Advanced Synthesis and Catalysis, 2018, vol. 360, # 4, p. 768 - 778]

35
[ 1239856-82-6 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
92.2%	In acetonitrile for 6h; Reflux;	3 Example 3 500 ml of acetonitrile was added to the oil and the mixture was warmed under stirring and refluxed for 6 h. The mixture was concentrated to a colorless oil and cooled to give 40.9 g of a white solid, namely 4-(S)-isobutyl-2-pyrrolidone. Yield: 92.2%

Reference： [1]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A Location in patent: Paragraph 0043

36
(S)-t-butyl 3-(aminomethyl)-5-methylhexanoate [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
92.5%	In acetonitrile for 5h; Reflux;	5 Example 5 500 ml of tetrahydrofuran was added to the oil and the mixture was warmed and stirred for 5 hours under reflux. The mixture was concentrated to give a colorless oil, which was cooled to give 41.0 g of a white solid, namely 4-(S)-isobutyl-2-pyrrolidone. Yield: 92.5% .

Reference： [1]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A Location in patent: Paragraph 0049

37
[ 779325-26-7 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
93.8%	In tetrahydrofuran for 2h; Reflux;	1 Example 1 400 ml of tetrahydrofuran was added to the oil, and the mixture was warmed with stirring and refluxed for 2 h. The mixture was concentrated to a colorless oil and cooled to give 41.6 g of a white solid, namely 4-(S)-isobutyl-2-pyrrolidone. Yield: 93.8%. .

Reference： [1]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A Location in patent: Paragraph 0028

38
C₁₀H₂₁NO₂ [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
91.2%	In tetrahydrofuran for 2h; Reflux;	2 Example 2 500 ml of tetrahydrofuran was added to the oil and the mixture was warmed and stirred for 2 hours under reflux. The mixture was concentrated to a colorless oil and cooled to give 40.4 g of a white solid, which was 4-(S)-isobutyl-2-pyrrolidone. Yield: 91.2% .

Reference： [1]Current Patent Assignee: JIANGXI KEWEI COLLABORATIVE INNOVATION PHARMACEUTI - CN107641093, 2018, A Location in patent: Paragraph 0041

39
C₉H₁₃NO₂ [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogen; bis(norbornadiene)rhodium(l)tetrafluoroborate; C₄₆H₃₈F₆FeN₂P₂S / 2,2,2-trifluoroethanol / 48 h / 30 °C / 60804.1 Torr 2: nickel dichloride; sodium tetrahydroborate; methanol

Reference： [1]Li, Xiuxiu; You, Cai; Yang, Yusheng; Yang, Yuhong; Li, Pan; Gu, Guoxian; Chung, Lung Wa; Lv, Hui; Zhang, Xumu [Chemical Science, 2018, vol. 9, # 7, p. 1919 - 1924]

40
methyl (S)-3-cyano-5-methyl-hexanoate [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	With methanol; sodium tetrahydroborate; nickel dichloride

Reference： [1]Li, Xiuxiu; You, Cai; Yang, Yusheng; Yang, Yuhong; Li, Pan; Gu, Guoxian; Chung, Lung Wa; Lv, Hui; Zhang, Xumu [Chemical Science, 2018, vol. 9, # 7, p. 1919 - 1924]

41
5-methyl-2-hexenoic acid tert-butyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / toluene / 30 h / 25 °C / Green chemistry 2: hydrogen; palladium 10% on activated carbon / methanol / 2 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A

42
5-methyl-2-hexenoic acid cyclohexyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / ethanol / 30 h / 25 °C / Green chemistry 2: hydrogen; 5% Pd(OH)₂/C / methanol / 12 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A

43
[ 181289-39-4 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
97.2%	With 5%-palladium/activated carbon; hydrogen In ethanol at 25℃; for 6h; Autoclave; Green chemistry;	15-16 Example 15: Preparation of intermediate 3 Will 50g of intermediate 2 ((S)-5-methyl-3-cyanohexanoic acid ethyl ester) dissolved in 300 mL of absolute ethanol, Add to the autoclave, Add 2.5g 5% Pd/C to the kettle, Passing hydrogen, Reaction at 25 ° C for 6 hours under a pressure of 5 MPa, The liquid phase detection intermediate 2 is completely converted, Stop stirring, Filtering, The filtrate was concentrated under reduced pressure. 37.4 g of Intermediate 3 were obtained in a yield of 97.2%.

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A Location in patent: Paragraph 0071; 0092-0096

44
(S)-5-methyl-3-cyanohexanoic acid p-chlorophenyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
88.5%	With 5%-palladium/activated carbon; hydrogen In ethanol at 25℃; for 4h; Autoclave; Green chemistry;	17 Example 15: Preparation of intermediate 3 General procedure: Will 50g of intermediate 2 ((S)-5-methyl-3-cyanohexanoic acid ethyl ester) dissolved in 300 mL of absolute ethanol, Add to the autoclave, Add 2.5g 5% Pd/C to the kettle, Passing hydrogen, Reaction at 25 ° C for 6 hours under a pressure of 5 MPa, The liquid phase detection intermediate 2 is completely converted, Stop stirring, Filtering, The filtrate was concentrated under reduced pressure. 37.4 g of Intermediate 3 were obtained in a yield of 97.2%.

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A Location in patent: Paragraph 0071; 0092-0094; 0097-0100

45
(S)-5-methyl-3-cyanohexanoic acid p-trifluoromethylphenyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
82.9%	With 5%-palladium/activated carbon; hydrogen In ethanol at 25℃; for 4h; Autoclave; Green chemistry;	18 Example 15: Preparation of intermediate 3 General procedure: Will 50g of intermediate 2 ((S)-5-methyl-3-cyanohexanoic acid ethyl ester) dissolved in 300 mL of absolute ethanol, Add to the autoclave, Add 2.5g 5% Pd/C to the kettle, Passing hydrogen, Reaction at 25 ° C for 6 hours under a pressure of 5 MPa, The liquid phase detection intermediate 2 is completely converted, Stop stirring, Filtering, The filtrate was concentrated under reduced pressure. 37.4 g of Intermediate 3 were obtained in a yield of 97.2%.

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A Location in patent: Paragraph 0071; 0092-0094; 0097-0099; 0101

46
(S)-5-methyl-3-cyanohexanoic acid tert-butyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
90.3%	With palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 2h; Autoclave; Green chemistry;	19 Example 15: Preparation of intermediate 3 General procedure: Will 50g of intermediate 2 ((S)-5-methyl-3-cyanohexanoic acid ethyl ester) dissolved in 300 mL of absolute ethanol, Add to the autoclave, Add 2.5g 5% Pd/C to the kettle, Passing hydrogen, Reaction at 25 ° C for 6 hours under a pressure of 5 MPa, The liquid phase detection intermediate 2 is completely converted, Stop stirring, Filtering, The filtrate was concentrated under reduced pressure. 37.4 g of Intermediate 3 were obtained in a yield of 97.2%.

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A Location in patent: Paragraph 0071; 0092-0094; 0097-0099; 0101

47
(S)-5-methyl-3-cyanohexanoic acid cyclohexyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
73.8%	With 5% Pd(OH)₂/C; hydrogen In methanol at 25℃; for 12h; Autoclave; Green chemistry;	20 Example 15: Preparation of intermediate 3 General procedure: Will 50g of intermediate 2 ((S)-5-methyl-3-cyanohexanoic acid ethyl ester) dissolved in 300 mL of absolute ethanol, Add to the autoclave, Add 2.5g 5% Pd/C to the kettle, Passing hydrogen, Reaction at 25 ° C for 6 hours under a pressure of 5 MPa, The liquid phase detection intermediate 2 is completely converted, Stop stirring, Filtering, The filtrate was concentrated under reduced pressure. 37.4 g of Intermediate 3 were obtained in a yield of 97.2%.

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A Location in patent: Paragraph 0071; 0092-0094; 0097-0099; 0101

48
5-methyl-2-hexenoic acid ethyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (S)-2,2'-dimethylammonium dimethyl-3,3'-diphenyl-1,1'-binaphthyl / water; hexane / 12 h / 20 °C / Green chemistry 2: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry
	Multi-step reaction with 2 steps 1: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / water; hexane / 15 h / 20 °C / Green chemistry 2: 5%-palladium/activated carbon; hydrogen / ethanol / 6 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A
[2]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A

49
5-methyl-2-hexenoic acid p-chlorophenyl ester [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-(9-methylanthracene)-((R)-(6-hydroxy-4-quinolinyl)phenoxymethyl-2-yl)-5-ethenyl-1-azabicyclo[2.2.2]octane / toluene; water / 12 h / 25 °C / Green chemistry 2: 5%-palladium/activated carbon; hydrogen / ethanol / 4 h / 25 °C / 37503.8 Torr / Autoclave; Green chemistry

Reference： [1]Current Patent Assignee: ZHEJIANG NHU CO., LTD. - CN109232311, 2019, A

50
[ 181289-33-8 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (3R)‐3‐(carbamoylmethyl)‐5‐methylhexanoic acid With sodium hypochlorite; sodium hydroxide In water at -10 - 50℃; for 7h; Stage #2: In water at 100 - 108℃; for 12h;	1.1; 2.1; 3.1 (1) Preparation of (S)-4-isobutylpyrrolidin-2-one: Add 250mL of water and 70g of sodium hydroxide to a 1000mL flask, stir to dissolve, cool to -5°C to 0°C, and then add 100g (0.53mol)(R)-(-)-3-( Carbamoylmethyl)-5-methylhexanoic acid (CAS181289-33-8), keep the reaction temperature below 0 during the addition, and then drop 355g of sodium hypochlorite aqueous solution with a mass fraction of 11.4%,After the addition, keep it under -10-0 for 2h,Slowly increase the temperature to 40-50°C, keep the reaction for 5h, then lower the temperature to 15°C, add dropwise about 55mL concentrated hydrochloric acid to adjust the pH to 8.5-9.0, and obtain the rearrangement reaction solution;At room temperature, the resulting rearrangement reaction solution was stirred and heated to reflux at 100-108°C, reacted at reflux for 12h, cooled to room temperature, extracted three times with 200ml of dichloromethane, combined organic layers, dried over anhydrous MgSO4, and concentrated under reduced pressure to obtain 72.54 g (S)-4-isobutylpyrrolidin-2-one with high purity, HPLC purity of 99.82%, and molar yield of 96.34%.

Reference： [1]Current Patent Assignee: ZHEJIANG BAMBOO PHARMACY - CN110963934, 2020, A Location in patent: Paragraph 0041-0044; 0050-0053; 0059-0062

51
[ 172796-25-7 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: methanol / 8 h / 70 °C / Inert atmosphere; Schlenk technique 1.2: 16 h / 20 °C / Inert atmosphere; Schlenk technique 2.1: ammonium cerium (IV) nitrate / water; acetonitrile / 16 h / 60 °C / Inert atmosphere; Schlenk technique

Reference： [1]Sietmann, Jan; Ong, Mike; Mück-Lichtenfeld, Christian; Daniliuc, Constantin G.; Wiest, Johannes M. [Angewandte Chemie - International Edition, 2021, vol. 60, # 17, p. 9719 - 9723][Angew. Chem., 2021, vol. 133, # 17, p. 9805 - 9810,6]

52
[ 691-37-2 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: zinc; trichlorophosphate / diethyl ether / 8 h / 40 °C / Inert atmosphere; Schlenk technique 1.2: 16 h / 20 - 80 °C / Inert atmosphere; Schlenk technique 2.1: methanol / 8 h / 70 °C / Inert atmosphere; Schlenk technique 2.2: 16 h / 20 °C / Inert atmosphere; Schlenk technique 3.1: ammonium cerium (IV) nitrate / water; acetonitrile / 16 h / 60 °C / Inert atmosphere; Schlenk technique

Reference： [1]Sietmann, Jan; Ong, Mike; Mück-Lichtenfeld, Christian; Daniliuc, Constantin G.; Wiest, Johannes M. [Angewandte Chemie - International Edition, 2021, vol. 60, # 17, p. 9719 - 9723][Angew. Chem., 2021, vol. 133, # 17, p. 9805 - 9810,6]

53
1-((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl)-4-isobutylpyrrolidin-2-one [ No CAS ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	With ammonium cerium (IV) nitrate In water; acetonitrile at 60℃; for 16h; Inert atmosphere; Schlenk technique;

Reference： [1]Sietmann, Jan; Ong, Mike; Mück-Lichtenfeld, Christian; Daniliuc, Constantin G.; Wiest, Johannes M. [Angewandte Chemie - International Edition, 2021, vol. 60, # 17, p. 9719 - 9723][Angew. Chem., 2021, vol. 133, # 17, p. 9805 - 9810,6]

54
[ 61312-87-6 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide; Lipase from Burkholderia cepacia / water / 6 h / 35 °C / pH 9 - 10 / Enzymatic reaction 2: cellobiose 2-epimerase / butan-1-ol / 10 h / 35 °C / Enzymatic reaction

Reference： [1]Current Patent Assignee: ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL; ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD. - US2021/114972, 2021, A1

55
[ 181289-22-5 ]
[ 181289-23-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With cellobiose 2-epimerase In butan-1-ol at 35℃; for 10h; Enzymatic reaction;	1.2; 2.2; 3.2; 4.2; 5.2 Step 2: Step 2: 15 g of R-configuration compound (C) obtained in step 1, 150 mL of n-butanol were added into a reaction flask, stirred and the temperature was raised to 35° C., 6 g of cellobiose 2-epimerase (producer: Shanghai Baoman Biological Technology Co., Ltd., purity 98%) was added, the temperature was kept and the reaction solution was stirred for 10 h, after the reaction was completed, the isomerase was removed by filtration, the filtrate was concentrated to about volume, 50 mL of water was added, cooled to 0-5° C., suction filtered and dried to obtain 14.1 g of S-configuration compound (D) with a yield of 94.0%, the product enantiomeric excess value e.e.: 99.72%.

Reference： [1]Current Patent Assignee: ZHEJIANG HUAHAI PHARMACEUTICAL CO., LTD.; ZHEJIANG HUAHAI ZHICHENG PHARMACEUTICAL - US2021/114972, 2021, A1 Location in patent: Paragraph 0044; 0047; 0050; 0053; 0056

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CAS No. :	181289-23-6	MDL No. :	MFCD19217624
Formula :	C₈H₁₅NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GUGXRXLTTHFKHC-ZETCQYMHSA-N
M.W :	141.21	Pubchem ID :	16101324
Synonyms :		Chemical Name :	(S)-4-Isobutylpyrrolidin-2-one

Num. heavy atoms :	10
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.88
Num. rotatable bonds :	2
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	45.37
TPSA :	29.1 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.32 cm/s

Log Po/w (iLOGP) :	1.87
Log Po/w (XLOGP3) :	1.19
Log Po/w (WLOGP) :	0.79
Log Po/w (MLOGP) :	1.16
Log Po/w (SILICOS-IT) :	1.71
Consensus Log Po/w :	1.34

[ CAS No. 181289-23-6 ] {[proInfo.proName]}

Quality Control of [ 181289-23-6 ]

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Product Details of [ 181289-23-6 ]

Calculated chemistry of [ 181289-23-6 ]

Physicochemical Properties

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[ 181289-23-6 ] Synthesis Path-Downstream 1~55

Related Functional Groups of
[ 181289-23-6 ]

Amides

Related Parent Nucleus of
[ 181289-23-6 ]

Pyrrolidines

Precautionary Statements-General

Prevention

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.33
Solubility :	6.56 mg/ml ; 0.0464 mol/l
Class :	Very soluble
Log S (Ali) :	-1.4
Solubility :	5.66 mg/ml ; 0.0401 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.9
Solubility :	1.78 mg/ml ; 0.0126 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.59

Signal Word:	Warning	Class:
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:
Hazard Statements:	H302-H315-H319-H335	Packing Group:
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 181289-23-6 ] {[proInfo.proName]}

Quality Control of [ 181289-23-6 ]

Related Doc. of [ 181289-23-6 ]

Product Details of [ 181289-23-6 ]

Calculated chemistry of [ 181289-23-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 181289-23-6 ]

Application In Synthesis of [ 181289-23-6 ]

[ 181289-23-6 ] Synthesis Path-Downstream 1~55

Related Functional Groups of [ 181289-23-6 ]

Amides

Related Parent Nucleus of [ 181289-23-6 ]

Pyrrolidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 181289-23-6 ]

Related Parent Nucleus of
[ 181289-23-6 ]