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[ CAS No. 94-62-2 ] {[proInfo.proName]}

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Chemical Structure| 94-62-2
Chemical Structure| 94-62-2
Structure of 94-62-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 94-62-2 ]

CAS No. :94-62-2 MDL No. :MFCD00005839
Formula : C9H15NO5 Boiling Point : -
Linear Structure Formula :- InChI Key :MXXWOMGUGJBKIW-YPCIICBESA-N
M.W : 285.34 Pubchem ID :638024
Synonyms :
Bioperine;1-Piperoylpiperidine;N-Piperoylpiperidin;NSC 21727

Calculated chemistry of [ 94-62-2 ]

Physicochemical Properties

Num. heavy atoms : 21
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.35
Num. rotatable bonds : 4
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 85.47
TPSA : 38.77 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.58 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.42
Log Po/w (XLOGP3) : 3.46
Log Po/w (WLOGP) : 2.51
Log Po/w (MLOGP) : 2.39
Log Po/w (SILICOS-IT) : 3.41
Consensus Log Po/w : 3.04

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.74
Solubility : 0.0524 mg/ml ; 0.000184 mol/l
Class : Soluble
Log S (Ali) : -3.96
Solubility : 0.0316 mg/ml ; 0.000111 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.0
Solubility : 0.287 mg/ml ; 0.001 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.92

Safety of [ 94-62-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 94-62-2 ]

* 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 [ 94-62-2 ]

[ 94-62-2 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 50838-22-7 ]
  • [ 120-57-0 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
95% With Aliquat 336; potassium carbonate In toluene at 90℃; for 10h;
88% With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dimethyl sulfoxide 1) 15 min, 25 deg C 2) 2 h, 60-65 deg C;
75.3% Stage #1: piperonal With sodium hydroxide In water; dimethyl sulfoxide for 0.5h; Stage #2: 1-crotonoylpiperidine In water; dimethyl sulfoxide at 20℃; 4.1.5 General procedure B for the synthesis of 3 General procedure: To a stirred solution of aromatic aldehyde (1.0 equiv, 2.4mmol) in DMSO (2mL), 1mL saturate sodium hydroxide solution was added and stirred for 30min. Then 2 (1.0 equiv, 2.4mmol) was added. Then stirred for another 6-8hat room temperature. Reaction was monitored by TLC. After completion, the reaction mixture was quenched with 5% aq. HCl and extracted with DCM, washed with water, dried over anhyd. Na2SO4 and concentrated under reduced pressure. The obtained crude product was purified by column chromatography.
With potassium hydroxide; N-benzyl-N,N,N-triethylammonium chloride In dimethyl sulfoxide at 60 - 65℃; for 2h; various solvents;
89 g With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide In water; dimethyl sulfoxide at 25 - 30℃; 3; 8 Preparation of piperine (I) To a well stirred mixture of (E) -l-(Piperidin-l-yl) but-2-en-l-one (100. Ogm, 0.653 moles), benzyl tri ethyl ammonium chloride (27. Ogm, 0.1 18 moles) in DMSO (1000 ml) was added piperonyl aldehyde (88. Ogm, 0.586 moles) at 25-30°C. Aq. NaOH (4.7gm 0.1 18 moles in 100 ml water) was added drop wise over a period of 45 min. The reaction mixture was then stirred at 25-30°C for 12-15 hours. After completion of reaction it was quenched in water (5000 ml) and further stirred at 25°C for 2.0 hrs. The precipitated solid was isolated by filtration, washed with water and dried under vacuum at 55-60 °C to yield title compound piperine as yellow solid.The crude piperine was purified by crystallization from 500 ml toluene to obtain crystalline solid.Yield: 89.0gm.HPLC Purity: 99.95%

  • 2
  • [ 110-89-4 ]
  • [ 136-72-1 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: piperic acid With thionyl chloride In dichloromethane at 20℃; Schlenk technique; Stage #2: piperidine In dichloromethane at 20℃; for 1h; Schlenk technique; Inert atmosphere; stereoselective reaction; General procedure: In a flame-dried Schlenk tube the carboxylic acid 4 (0,20 mmol,1.0 equiv.) was dissolved in anhydrous DCM (1 mL), followed bythe addition of thionyl chloride (0.40 mmol, 2.0 equiv.). Thereaction was stirred at room temperature until the solid dissolvedcompletely. Heating to reflux can be applied for a faster conversion. Thereafter, volatiles were removed under reducedpressure, and the flask was flushed with argon again (an argonfilledballoon was attached to the rotary evaporator). To theresulting residue anhydrous DCM was added (1 mL), and theamine was added dropwise (0.40 mmol, 2.0 equiv.). Afterwards,the solution was stirred for 1 h at room temperature. Finally, thereaction mixture was quenched and washed with saturatedaqueous NaHCO3 solution, and the aqueous layer was extracted3 times with DCM. The combined organic layer was dried overNa2SO4, filtered, and volatiles were removed under reducedpressure to yield the pure amide. Further purification via flashchromatography gave the desired amide. (Gradient: EtOAc/heptane10:90 to EtOAc/heptane 60:40).
93% With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 8h;
90% With N,N-bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride; triethylamine In dichloromethane at 20 - 25℃; for 1h;
72% With dmap; dicyclohexyl-carbodiimide
71% With dmap; dicyclohexyl-carbodiimide In dichloromethane for 18h; Inert atmosphere; 1 Synthesis of Compound of Piperine Accurately weigh III (218 mg, 1 mmol),Hexahydropyridine (102mg, 1.2 mmol),Dichloromethane was added to completely dissolve. Under argon, dicyclohexylcarbodiimide (DCC) (226 mg, 1.1 mmol) and 3-dimethylaminopyridine (DMAP)(13.2 mg, 0.11 mmol) was dissolved in dichloromethane and added dropwise to the reaction system. The reaction was carried out for 18 h under the protection of nitrogen, and monitored by thin layer chromatography (until the reaction was completed. After the reaction was completed, suction filtration was repeated for many times, and the organic phase was retained. It was washed with saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain the target compound Piperine (71% yield).

  • 4
  • [ 14064-10-9 ]
  • [ 94-62-2 ]
  • [ 6174-95-4 ]
  • [ 139059-85-1 ]
YieldReaction ConditionsOperation in experiment
1: 70% 2: 24% With selenium; caesium carbonate In acetonitrile Heating;
  • 5
  • [ 14064-10-9 ]
  • [ 94-62-2 ]
  • [ 139059-84-0 ]
YieldReaction ConditionsOperation in experiment
80% With caesium carbonate; sulfur In acetonitrile Heating;
  • 6
  • [ 94-62-2 ]
  • [ 23434-88-0 ]
YieldReaction ConditionsOperation in experiment
98% With zinc copper In methanol for 3h; Heating;
98.5% With 5% Pd/C; hydrogen for 4h;
97% With 5% Pd(II)/C(eggshell); hydrogen In dichloromethane for 12h;
95% With palladium on activated charcoal; hydrogen In methanol for 6h;
90% With hydrogen In ethyl acetate for 2h;
78% With hydrogen In ethanol for 0.5h;
With hydrogen In ethanol for 3h;
With hydrogen
With hydrogen In methanol for 2h;
With palladium on activated charcoal; hydrogen for 2h;
With palladium on activated charcoal; hydrogen for 12h;
14 g With palladium 10% on activated carbon; hydrogen In methanol at 40 - 45℃; 4 Preparation of Tetrahydro Piperine ( la) To a 1.0 lit hydrogenator, piperine (15.0 gms, 0.052 moles) along with methanol (140ml) was charged at 25-30°C. In another beaker slurry of 10% Pd/C (1.5 gm, 50 % wet) in 10.0 ml of methanol was prepared and charged into above reaction mass at 25-30°C. The hydrogen pressure (40-50 PSI) was applied and maintained reaction at 40-45°C for 10-12 hrs. Reaction mixture was cooled to 25-30°C and filtered through hyflo to remove catalyst and the bed was washed with methanol (15 ml). Distilled out methanol under vacuum below 45°C. Added n-Heptane (100 ml) and stirred for 12-13hrs. The precipitated solid was isolated by filtration, washed with n-Heptane and dried under vacuum at 35-40 °C to obtain title compound tetrahydropiperine as white solid.Yield: 14.0 gms,Purity: 99.5%

Reference: [1]Sondengam, B. Lucas; Fomum, Z. Tanee; Charles, Georges; Akam, T. Mac [Journal of the Chemical Society. Perkin transactions I, 1983, p. 1219 - 1222]
[2]Location in patent: experimental part Sangwan, Payare L.; Koul, Jawahir L.; Koul, Surrinder; Reddy, Mallepally V.; Thota, Niranjan; Khan, Inshad A.; Kumar, Ashwani; Kalia, Nitin P.; Qazi, Ghulam N. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 22, p. 9847 - 9857]
[3]Location in patent: experimental part Correa, Edwin Andrés; Högestätt, Edward D.; Sterner, Olov; Echeverri, Fernando; Zygmunt, Peter M. [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 9, p. 3299 - 3306]
[4]Location in patent: experimental part Pedersen, Mikael E.; Metzler, Bjorn; Stafford, Gary I.; Van Staden, Johannes; Jaeger, Anna K.; Rasmussen, Hasse B. [Molecules, 2009, vol. 14, # 9, p. 3833 - 3843]
[5]Ribeiro, Tatiana Santana; Freire-De-Lima, Leonardo; Previato, Jose Osvaldo; Mendonca-Previato, Lucia; Heise, Norton; De Lima, Marco Edilson Freire [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 13, p. 3555 - 3558]
[6]Venkatasamy, Radhakrishnan; Faas, Laura; Young, Antony R.; Raman, Amala; Hider, Robert C. [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 8, p. 1905 - 1920]
[7]Nakamura, Norio; Kiuchi, Fumiyuki; Tsuda, Yoshisuke [Chemical and pharmaceutical bulletin, 1988, vol. 36, # 7, p. 2647 - 2651]
[8]Jain, A. K.; Sharma, N. D.; Gupta, S. R. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1986, vol. 25, p. 979]
[9]Ablordeppey, Seth Y.; Fischer, James B.; Glennon, Richard A. [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 8, p. 2105 - 2111]
[10]Location in patent: scheme or table Mu, Li-Hua; Wang, Bo; Ren, Hao-Yang; Liu, Ping; Guo, Dai-Hong; Wang, Fu-Meng; Bai, Lin; Guo, Yan-Shen [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 9, p. 3343 - 3348]
[11]Fokoue; Marques; Correia; Yamaguchi; Qu; Aires-De-Sousa; Scotti; Lopes; Kato [RSC Advances, 2018, vol. 8, # 38, p. 21407 - 21413]
[12]Current Patent Assignee: CIPLA LTD - WO2019/73491, 2019, A1 Location in patent: Page/Page column 9; 15
  • 7
  • [ 94-62-2 ]
  • 4,5-(trans)-2,3-epoxy piperylpiperidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With dihydrogen peroxide at 37℃; for 18h; Horseradish peroxidase, 0,1M sodium phosphate buffer, pH 6,5;
  • 8
  • [ 94-62-2 ]
  • [ 136-72-1 ]
YieldReaction ConditionsOperation in experiment
98% Stage #1: Piperine With potassium hydroxide for 48h; Reflux; Stage #2: With glacial acetic acid In lithium hydroxide monohydrate 4.1.2. Preparation of the key intermediate piperinoyl azidederivative (3) Piperine (5 g, 17.5 mmol) was refluxed in 20% alcoholic KOH(150 mL) for 48 h to produce potassium-piperate. Ethanol wasvacuo-removed, and the ppt.was redissolved in 100mL boiling H2Oand acidified with acetic acid to liberate the free piperic acid (ppt.),which was vacuum-filtered, and recrystallized from hot ethyl acetateto produce crystalline piperic acid (3.75 g, 98% yield).
98% With ethanol; potassium hydroxide Reflux;
96.4% With lithium hydroxide monohydrate; potassium hydroxide In ethanol for 18h; Reflux; 1 [Example 1] (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid Piperine (8 g, 28.0 mmol) and potassium hydroxide (18.9 g, 336 mmol) were added, dissolved in ethanol (95 mL) and water (5 mL), and the temperature was raised and refluxed for 18 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, the pH was adjusted to 1 with 1N aqueous hydrogen chloride solution, and the resulting solid was filtered under reduced pressure and dried under vacuum. (5.9 g, 96.4%)
94% With potassium hydroxide In methanol at 150℃; for 24h;
94.5% Stage #1: Piperine With potassium hydroxide In ethanol for 20h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate
94.5% With potassium hydroxide In ethanol for 20h; Reflux; Preparation of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid (piperic acid) (2) In a 50 mL flask, 2.20 g (7.72 mmol) of piperine and 22 mL of the ethanolic solution of 20% KOH were added.The reaction mixture was refluxed with stirring for 20 h. At the end of the reaction, the mixture was filtered, and the precipitate formed was washed with ethanol and dried. The precipitate was dissolved in water and acidified with 10%HCl solution down to pH 3. The yellowish precipitate formed was filtered out, washed with water, dried and recrystallized in ethanol.8 Piperic acid was obtained at 1.67 g (94.5% yield) with the following characteristics. MW 218.21 g mol-1;mp 217-218 °C (lit.:17 216-217 °C); IR (ATR) ν / cm-1 3448(O-H), 2922 (C-HAliph), 1676 (C=O), 1604-1419 (C=CAr),1255 (C-O-C), 927 (C-HAr); 1H NMR (400 MHz, CDCl3) δ 12.20 (s, 1H, O-H), 7.36-7.26 (m, 1H, CHolef), 7.23 (s, 1H,CHAr), 7.03-6.89 (m, 4H, CHAr and CHOlefin), 6.05 (s, 2H,O-CH2-O), 5.93 (d, J 15.2 Hz, 1H, CHAr); 13C NMR(101 MHz, CDCl3) δ 168.1, 148.5, 148.4, 145.1, 140.2,130.9, 125.3, 123.5, 121.5, 108.4, 106.1, 101.8.
94.5% With potassium hydroxide In ethanol for 20h; Reflux; Preparation of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid (piperic acid) (2) The mixture of 2.20 g (7.72 mmol) of piperine and22 mL of 20% KOH (ethanolic solution) was subjected toreflux and agitation for 20 h. After the end of reaction, themixture was filtered, washed with ethanol and dried. Theprecipitate formed was solubilized in water and acidifiedwith HCl solution 10% down to pH 3. The precipitateformed with a yellowish coloration was filtered, washedwith water, dried and recrystallized in ethanol.18 Yield:94.5% (1.67 g); MW 218.21 g mol-1; mp 217-218 °C(lit.:18 216-217 °C); IR (ATR) / cm-1 3448 (O-H),2922 (C-HAliph), 1676 (C=O), 1604-1419 (C=CAr), 1255(C-O-C), 927 (C-HAr); 1H NMR (400 MHz, CDCl3)d 12.20 (s, 1H, O-H), 7.36-7.26 (m, 1H), 7.23 (s, 1H),7.03-6.89 (m, 4H), 6.05 (s, 2H), 5.93 (d, J 15.2 Hz, 1H);13C NMR (101 MHz, CDCl3) d 168.1, 148.5, 148.4, 145.1,140.2, 130.9, 125.3, 123.5, 121.5, 108.4, 106.1, 101.8.
93% With potassium hydroxide In ethanol for 24h; Heating;
93% With potassium hydroxide In ethanol for 16h; Reflux; Synthesis of piperic acid (2) A mixture of piperine (4 g, 14 mmol) and KOH (9.4 g, 168 mmol) in 95% ethanol (34 mL) was reuxed. When the reaction was complete checked by TLC after 16 h, the mixture was filtered, and the obtained solid was dissolved with H2O, whose pH value was adjusted by 1 M aq. HCl to 2-3. Then the obtained precipitate was ltered and washed with icewater to afford 2 (1.43 g, 93% yield) as a pale yellow solid.
93.4% With methanol; potassium hydroxide for 48h; Reflux;
93.1% With potassium hydroxide In methanol at 75℃; for 24h; 2.2.1. (2E,4E)-5-(Benzo[d][1,3]dioxol-5-yl)penta-2,4-dien-oicAcid (1, C12H10O4). (2E,4E)-5-(Benzo[d][1,3]dioxol-5-yl)penta-2,4-dien-oic acid (1) was prepared by the improved alkaline hydrolysis method according to the method reportedby Inder Pal et al. [16]. -e method reported in theliterature is to directly acidify with hydrochloric acid [16],and the consumption of hydrochloric acid is large. In thisexperiment, the potassium salt of the compound was separatedfrom the system ;rstly, followed by the pH adjustmenttreatment, and the recrystallization operation isomitted. -e experimental yield has reached more than 90%.In brief, piperine (10.69 g, 37.51 mmol) was dispersed in aKOH methanol solution (mass fraction 20%, 300 mL) andreMuxed at 75°C for 24 h. -e suspension was then cooled,and a white solid was obtained after suction ;ltration. -esolid was dispersed in a small amount of methanol. -e pHwas adjusted to 1 using 6 mol/L hydrochloric acid. -esuspension was then ;ltered through suction and dried toa
93.1% With potassium hydroxide In methanol at 75℃; for 24h; 2.2.1. (2E, 4E)-5-(Benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic Acid(1, C12H10O4). Piperine (10.69 g, 37.51 mmol) wasdispersed in a potassium hydroxide (KOH) (237 g,4.22 mol)/methanol solution (300 mL) and reuxed at 75°C.After 24 h, the solution was cooled and subjected to suction filtration to obtain a white solid. )e solid was dispersed in small amounts of methanol, and 6 mol/L hydrochloric acid was used to adjust the pH level to one. Following this,suction filtration was conducted, after which the substance was dried to obtain compound 2. )e product was a yellowpowder with a mass of 7.61 g and a yield of 93.1%. 1H NMR(400 MHz, DMSO-d6): 6 12.21 (s, 1H, -COOH), 7.30 (ddd,J 15.3, 7.0, 3.4 Hz, 1H, CHCH-CO), 7.24 (d, J 1.7 Hz,1H, Ar-H), 7.03-6.79 (m, 3H, Ar-H, Ar-CHCH-), 6.93 (d,J 8.0 Hz, 1H, Ar-CHCH-), 6.06 (s, 2H, -OCH2O-), 5.93(d, J 15.2 Hz, 1H, CHCH-CO). 13C NMR (101 MHz,DMSO-d6): 6 168.03, 148.56, 148.45, 145.01, 140.21, 131.00,125.33, 123.51, 121.63, 108.97, 106.20, 101.82.
93% With methanol; potassium hydroxide for 48h; Reflux;
92% With potassium hydroxide In methanol for 24h; Reflux;
92.4% With potassium hydroxide In ethanol at 20℃; Reflux;
91% With potassium hydroxide In ethanol for 8h; Reflux; 1 Add 2.85 g (10 mmol) of piperine to 10 mL of ethanol solution containing 20% KOH, heat at reflux for 8 h, cool, dilute ρΗ2-3 with dilute hydrochloric acid, concentrate, add 20 mL of water, stir, extract with chloroform, dry, Crystallization was concentrated to give pepper acid with a yield of 91%.
90% With potassium hydroxide In ethanol for 24h; Heating;
90% With potassium hydroxide In ethanol for 25h; Reflux;
90% Stage #1: Piperine With ethanol; potassium hydroxide for 2h; Reflux; Cooling with ice; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate Preparation of piperic acid Piperine (0.35 mmol) was refluxed with ethanolic KOH(2 mol L-1) for 2 h. Ethanol was evaporated under reducedpressure and cooled in ice salt bath. The solid potassiumsalt of piperic acid was suspended in hot water and acidifiedwith hydrochloric acid, yellow precipitate was collected,washed with cold water and recrystallized from ethanolyielding 68.8 mg of piperic acid (90% yield).
90% With potassium hydroxide In methanol at 20℃; for 48h; 1 2.2 Synthesis of compounds 3a-u To a solution of Piperine (1; 10g, 35mmol) in CH3OH (200mL) was added powdered KOH (20g) and the reaction mixture was stirred at room temperature for 48h. The reaction mixture was concentrated under reduced pressure. The reaction mixture was acidified with 2N HCl and the resulting precipitate was filtered and washed with cold H2O to give (2E,4E)-piperinic acid 2 (6.9g, 90%). A solution of compound 2 (1g, 4.58mmol) and Et3N (1.15mL, 8.25mmol) in anhydrous CH2Cl2 (50mL) was cooled to 0°C. To the cooled reaction mixture was added CH3SO2Cl (0.53mL, 6.84mmol) and the reaction mixture was stirred at 0°C for 45min till complete consumption of the starting material. To the reaction mixture was added amine (5mmol) and the reaction mixture was stirred at room temperature for 2h. The reaction mixture was diluted with CH2Cl2 (100mL) and the organic layer washed with satd. NaHCO3 (50mL) and H2O (50mL), dried (Na2SO4) and concentrated. The crude product was purified over SiO2 using hexane-EtOAc (4:1) as eluant to give pure compounds 3a-u
88% Stage #1: Piperine With lithium hydroxide monohydrate; potassium hydroxide In methanol for 72h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate
86.6% Stage #1: Piperine With potassium hydroxide In ethanol for 10h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate Hydrolysis of piperine to piperic acid Piperine (10 g) and 300 ml 20 % ethanolic KOH were taken in a round-bottomed flask and refluxed for 10 h. The resulting potassium piperate was filtered and washed with anhydrous ethanol. The precipitate was dissolved in distilled water, and 0.1 M HCl was added to the solution, followed by filtering and washing with distilled water. Yellow crystals of piperic acid were recrystallized from ethanol [34] (yield 86.6 %, m.p. 214-216 C).
86.6% Stage #1: Piperine With potassium hydroxide In ethanol for 10h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate Piperic acid Piperine (10 g) was dissolved in300 mL of anhydrous ethanol containing 20% KOH and the mixture was refluxed upon stirring for 10 h to give the precipitate of potassium piperate, which was filtered off and washed with anhydrous ethanol. The precipitate was dissolved in distilled water and precipitated upon addition of HCl solution (0.1 M). The yellow precipitate of piperic acid was fi ltrated off and washed with distilled water (200 mL) to give powdery yellow piperic acid [20],yield 86.6%, mp 214-216°C.
85% With lithium hydroxide In ethanol; lithium hydroxide monohydrate for 140h; Heating;
83% Stage #1: Piperine With lithium hydroxide monohydrate; potassium hydroxide In ethanol at 90℃; for 16h; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate
83.3% With sodium hydroxide In methanol for 24h; Darkness; Reflux; 2.4.1 Synthesis of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid (piperic acid, 2) In a double neck round bottom flask a methanolic solution of NaOH 2M (26.4mL, 52.8mmol) was added to piperine (compound 1) (3.01g, 10.6mmol). The mixture was protected from the light and refluxed for 24h. Once the reaction was complete, water (30mL) was added and the mixture was acidified with HCl 6Mat 0°C. The solid was isolated by filtration under reduced pressure and washed with methanol and dichloromethane. TLC analysis was performed in dichloromethane/methanol/formic acid (9:1:0.001). The procedure was adapted from Venkatasamy etal. [15] with slight modifications. Yield (%): 83.3; ESI/MS m/z (%): 219 (M++1, 100).
82% With sodium hydroxide In ethanol for 1h; Microwave irradiation;
82% With potassium hydroxide In ethanol for 22h; Reflux; Procedure for Preparation of 5-(3,4-Methylenedioxyphenyl)-2E,4E-pentadienoic Acid (Piperic Acid, 2) A solution of piperine (5.14 g, 18.0 mmol), purchased from WakoPure Chemical Industries, Ltd., in ethanol (220 mL) was refluxedfor 22 h in the presence of KOH (45 g). After completionof hydrolysis, the solvent was evaporated under reducedpressure. The resulting reaction mixture was suspended inwater (100 mL) and acidified with 4 N HCl to pH <1. Theresultant pale brown precipitate was collected by filtration,washed with cold water and recrystallized from methanol to give crystals of piperic acid (2, 3.2 g, 82%). Pale brownsolid. mp 225-226°C (lit.20) 212-215°C). 1H-NMR (DMSO-d6,400 MHz) δ: 7.31-7.24 (1H, m, H-3), 7.22 (1H, d, J=1.6 Hz,H-2), 6.99 (1H, dd, J=8.0, 1.6 Hz, H-6), 6.98-6.93 (2H,m, H-4 and H-5), 6.91 (1H, d, J=8.0 Hz, H-5), 6.03 (2H, s,-OCH2O-), 5.90 (1H, d, J=15.2 Hz, H-2). MS (electron ionization(EI)) m/z: 218 [M]+.
80% Stage #1: Piperine With potassium hydroxide In ethylene glycol at 180℃; Stage #2: With hydrogenchloride; lithium hydroxide monohydrate In ethylene glycol
80% With methanol; potassium hydroxide for 6h; Reflux;
80% With potassium hydroxide In ethylene glycol at 180℃;
79.1% With potassium hydroxide In ethanol for 12h; Reflux; 1 Synthesis of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid Synthesis of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid Piperine (200 mg, 0.70 mmol) dissolved in anhydrous ethanol and KOH (1.18 g, 21.0 mmol) were mixed and heated to reflux for 12 hours. Upon completion of the experiment, the pH value of the reaction mixture solution was adjusted to 2-3 using hydrochloric acid. After the ethanol was distilled under reduced pressure, the residue was diluted with EtOAC (30 mL) and washed with a saturated solution of NaCl, followed by drying over anhydrous Na2SO4. The solvent was distilled under reduced pressure to give a target compound (121 mg, yield: 79.1%). 1H NMR (500 MHz, Acetone) d 7.37-7.42 (ddd, 1H, J=5.1 Hz), 7.17 (d, 1H, J=1.8 Hz), 7.03 (dd, 1H, J=1.8 Hz), 6.96 (dd, 1H, J=1.4 Hz), 6.85 (d, 1H, J=7.8 Hz), 6.04 (s, 2H), 5.96-5.99 (d, 2H, J=15.2 Hz).
79.1% With potassium hydroxide In ethanol for 12h; Reflux; 1 Synthesis of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid Synthesis of (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoic acid Piperine (200 mg, 0.70 mmol) dissolved in anhydrous ethanol and KOH (1.18 g, 21.0 mmol) were mixed and heated to reflux for 12 hours. Upon completion of the experiment, the pH value of the reaction mixture solution was adjusted to 2-3 using hydrochloric acid. After the ethanol was distilled under reduced pressure, the residue was diluted with EtOAC (30 mL) and washed with a saturated solution of NaCl, followed by drying over anhydrous Na2SO4. The solvent was distilled under reduced pressure to give a target compound (121 mg, yield: 79.1%). 1H NMR(500 MHz, Acetone) d 7.37-7.42(ddd, 1H, J = 5.1 Hz), 7.17(d, 1H, J = 1.8 Hz), 7.03(dd, 1H, J = 1.8 Hz), 6.96(dd, 1H, J = 1.4 Hz), 6.85(d, 1H, J = 7.8 Hz), 6.04(s, 2H), 5.96-5.99(d, 2H, J = 15.2 Hz).
65% With potassium hydroxide In ethylene glycol at 180℃;
60% With potassium hydroxide In methanol for 2h; Heating;
18.03% With potassium hydroxide In methanol for 24h; Reflux; Inert atmosphere; 3.3.1. Preparation of Piperic Acid (2) Natural piperine (1), the starting material, was added to a round-bottom flask (10.0g, 35.05 mmol) and dissolved in methanol (200 mL), and a 20% w/v solution of sodiumhydroxide (200 mL) was added. The mixture was refluxed for 24 h. After cooling to roomtemperature, the mixture was filtered to remove the solid residues and concentrated underreduced pressure to remove the volatile solvent. The filtrate was neutralized with 1 Mhydrochloric acid (HCl) until it reached pH 1. The resulting yellow solid was collected byfiltration and washed with cold water (100 mL, 3 times). The filtrate was further extractedby dichloromethane (100 mL, 3 times), washed with water (100 mL, 3 times), and concentratedunder reduced pressure to obtain a yellow solid. The yellow solid was combinedand recrystallized in methanol to afford piperic acid (2) at 1.38 g (18.03% yield). IR (ATR,νmax) 2916, 1668, 1616, 1596, 1500, 1489, 1446, 1417, 1367, 1309, 1255, 1191, 1147, 1100, 1034,991, 938, 920, 852, 806, 789, 696, 607, 607, 582 cm-1; 1H-NMR (400 MHz, acetone-d6) δH: 7.40(m, 1H, H-3), 7.17 (d, J = 1.6 Hz, 1H, H-12), 7.03 (dd, J = 1.6 and 8.0 Hz, 1H, H-7), 6.98 (d, J= 10.0 Hz, 1H, H-4), 6.97 (d, J = 5.6 Hz, 1H, H-5), 6.86 (d, J = 8.0 Hz, 1H, H-8), 6.04 (s, 2H,H-10), 6.00 (d, J = 15.2 Hz, 1H, H-2) ppm; 13C-NMR (100 MHz, acetone-d6) δC: 167.9 (C-1),149.6 (C-11), 149.5 (C-9), 146.1 (C-3), 141.0 (C-5), 131.9 (C-6), 125.7 (C-4), 124.0 (C-7), 121.4(C-2), 109.3 (C-8), 106.6 (C-12), 102.5 (C-10) ppm; HRMS m/z 219.0650 ([M + H]+, calculatedfor C12H11O4, 219.0657).
With sodium hydroxide In ethanol
Stage #1: Piperine With potassium hydroxide In ethanol for 3h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate General synthetic proceduresFormation of piperic acidPiperine was dissolved in 2 N ethanolic KOH and refluxed for 3 days.Afterwards the reaction mixture was evaporated. The residue was dissolved in ice- water and acidulated with 2 N HCI. The precipitate was filtered, excessively washed with water and dried. The resulting crude product was crystallized from ethanol to give piperic acid as yellow crystals (melting point (mp.) 219-220°C).
With potassium hydroxide
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / Reflux 2: sulfuric acid / lithium hydroxide monohydrate
Stage #1: Piperine With potassium hydroxide In methanol for 6h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate Cooling with ice;
With methanol; potassium hydroxide for 48h; Reflux; 5.2. Preparation of piperic acid (1) Piperine (2 g) was dissolved in 200 ml of methanol containing 20% KOH in a 500 ml reaction flask. The reaction mixture was refluxed with stirring for 48 h. After completion of hydrolysis and removal of methanol under reduced pressure, a yellow colored oily solid was obtained which was then dissolved in water (100 mL) and acidified with HCl yielding yellowish precipitate of piperic acid. Crystallization with methanol gave yellow needle shaped crystals.
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 8 h / Reflux 2: hydrogenchloride / lithium hydroxide monohydrate / pH 1 - 2
With ethylene glycol; potassium hydroxide Reflux;
With sodium hydroxide In ethanol for 24h; Reflux;
With potassium hydroxide In ethanol Reflux; Piperine was taken in ethanolic KOH and reflux for 3-4 h.Piperic acid formation was confirmed by the TLC (thin layerchromatography) analysis by using the TLC system (Ethylacetate: hexane, 4:6). Reaction mixture was than acidified to afford the piperic acid in the form of precipitates which were filtered and washed with distilled water and dried. Piperic acid was esterified in the presence of sulfuric acid as catalyst in ethanol under reflux for 12 h to produced ethyl piperate.Than ethyl piperate and hydrazine hydrate were taken in ethanol and refluxed for 4 h to produce hydrazide of piperic acid (b). Chemical structure of compound (b) was confirmedby different spectroscopic techniques such as EI-MS, 1HNMRand IR
With potassium hydroxide In ethanol for 10h; Reflux; Synthesis of piperic acid: The was prepared using 0.118 mol of piperine and 20 % EtOH-KOH (300 mL) for 10 h reflux and then washed with ethanol (99 % purity). The potassium piperate was then treated with 0.1 M HCl and then washed with distilled water (Scheme-I). Then piperic acid (yellow colour) was recrystallized with ethanol.
7 g With potassium hydroxide In 1,2-dimethoxyethane at 115℃; 5 Preparation of Piperic acid (lb) Charged piperine (15.0gm, 0.052 moles) with ethylene glycol( 150 ml) at 25-30°C into reaction flask, added potassium Hydroxide (13.3 gm, 0.238 moles) at 25-30°C. Temperature of the reaction was increased to 115°C and maintained for 14-15 hrs. After completion of reaction, the reaction mixture was cooled to 15-20°C and added water (150 ml) into reaction mixture followed by acidification with 15.0 ml of Cone. HC1. Reaction mixture was stirred further for 1.0 hr at 15-20°C and the precipitated solid was filtered, washed with water. Wet cake was charged into reaction flask along with methanol (55 ml) and stirred for 1.0 hr. at 25-30°C. The solid was isolated by filtration, washed with 15 ml of methanol and under vacuum at 25-30°C to give title compound piperic acid.Yield: 7.0 gm.HPLC Purity: 96.5%
With potassium hydroxide
With sodium hydroxide In methanol for 24h; Reflux;
With lithium hydroxide monohydrate
With potassium hydroxide In ethanol for 12h; Reflux;
Stage #1: Piperine With sodium hydroxide In ethanol for 24h; Reflux; Stage #2: With hydrogenchloride In lithium hydroxide monohydrate
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol / 72 h / 80 °C 2: hydrogenchloride / lithium hydroxide monohydrate / 0.5 h / 20 °C

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  • 9
  • [ 10043-37-5 ]
  • [ 202998-56-9 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
38% With palladium diacetate; triethylamine; triphenylphosphine; lithium chloride In acetonitrile at 70 - 80℃; for 18h;
  • 10
  • [ 94-62-2 ]
  • [ 23434-88-0 ]
  • (E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)pent-4-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 14% 2: 58% With sodium tetrahydroborate; iodine In tetrahydrofuran at 0℃; for 0.333333h;
  • 11
  • [ 94-62-2 ]
  • (E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)pent-4-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With sodium tetrahydroborate; iodine In tetrahydrofuran at 0℃; for 0.333333h;
  • 12
  • [ 94-62-2 ]
  • [ 23512-55-2 ]
  • cis-5-benzo[1,3]dioxol-5-yl-1-piperidin-1-yl-pent-3-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With acetic acid; zinc for 2h; Ambient temperature;
1: 80 % Chromat. 2: 20 % Chromat. With ethylene dibromide; sodium iodide In water; N,N-dimethyl-formamide Electrochemical reaction;
  • 14
  • [ 10043-37-5 ]
  • [ 2373-80-0 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
51% Stage #1: 3,4-methylenedioxy-trans-cinnamic acid With N-Bromosuccinimide; tetrabutylammonium trifluoroacetate In 1,2-dichloro-ethane at 20℃; for 4h; Stage #2: N-acrylpiperidine With palladium diacetate; triphenylantimony; triethylamine In 1,2-dichloro-ethane for 20h;
  • 15
  • [ 94-62-2 ]
  • SCT-63 [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With diisobutylaluminium hydride In toluene at -10℃; for 0.5h;
34% With lithium aluminium tetrahydride In tetrahydrofuran for 72h; Inert atmosphere;
13% With sodium tetrahydroborate; iodine In tetrahydrofuran at 0℃; for 48h;
With lithium aluminium tetrahydride In diethyl ether for 24h; Heating;
With sodium tetrahydroborate; iodine In tetrahydrofuran at 0℃; for 48h; Inert atmosphere;

  • 16
  • [ 94-62-2 ]
  • (5-(benzo[d][1,3]dioxol-5-yl)thiophen-2-yl)(piperidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
23% With naphthalene-1,8-trisulfide-2-oxide In chlorobenzene for 16h; Heating;
  • 17
  • [ 94-62-2 ]
  • (2E,4E)-5-(3,4-dihydroxyphenyl)-1-(piperidin-1-yl)penta-2,4-dien-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
76.2% With boron tribromide In dichloromethane at 20℃; for 48h;
53% With boron tribromide In dichloromethane at -15 - 20℃; for 24h; Deprotection of piperine by BBr3 method To a solution of piperine (500 mg, 1.75 mmol, 1 eq) in dichloromethane (DCM, 10 mL) at -15 °C,a dichloromethane solution of BBr3 (0.7 mL, 8.7 mmol, 5 equiv) was added at and slowly warmedto room temperature and stirring continued for 24 h. After the completion, DCM was removedunder vacuum to yield yellow solid. It was then with water, DCM, and dried. The pure productwas obtained by column purification, 254 mg (53%).Physical Characteristics:Colour and appearance: Pale yellow solidM.pt: 183 °C - 186 °C.Spectral data:1H NMR (500 MHz, DMSO) δ: 1.47-1.60 (6H, m), 6.65 (1H, d, J = 15 Hz), 6.73 (1H, d, J = 10Hz), 6.78-6.83 (3H, m), 6.93 (1H, s), 7.21 (1H, dd, J = 15 Hz, J = 10 Hz).13CNMR (125 MHz, DMSO) δ: 24.6, 25.8, 26.9, 42.9, 114.0, 116.2, 119.9, 120.1, 124.5, 128.4,139.0, 142.7, 145.9, 147.0, 164.9.IR (KBr) cm-1: 3453, 3116, 1627, 1612, 1561, 1449, 1253, 1003, 854.Elemental analysis calcd for C16H19NO3: C = 70.31; H = 7.01; N = 5.12. Found: C = 70.23; H =7.03; N = 4.77.
50% With boron tribromide In dichloromethane at 0 - 20℃; for 16h;
50% With boron tribromide In dichloromethane at 0 - 20℃; for 16h;
44% With boron tribromide In dichloromethane at -15 - 20℃; for 24h; Deprotection of piperine by BBr3 method To a solution of piperine (500 mg, 1.75 mmol, 1 eq) in dichloromethane (DCM, 10 mL) at -15 °C, a dichloromethane solution of BBr3 (0.7 mL, 8.7 mmol, 5 equiv) was added at and slowly warmed to room temperature and stirring continued for 24 h. After the completion, DCM was removed under vacuo to yield yellow solid. The yellow solid was washed with water, DCM and dried. The pure product was obtained by column purification, 210 mg (44%).
31.3% With boron tribromide In dichloromethane; water at 0 - 20℃; for 24h; 2 [Example 2] (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (1, AJ-2137) Piperine (1 g, 3.50 mmol) was dissolved in dichloromethane, and an aqueous boron tribromide solution was slowly added dropwise at 0°C.The temperature was raised to room temperature and stirred for 24 hours. After completion of the reaction, ethyl acetate and water were added, and the organic layer was dried with anhydrous sodium sulfate and then distilled under reduced pressure to remove the solvent.The compound was obtained by column chromatography. (300 mg, 31.3%)
With boron tribromide In dichloromethane at 20℃; for 48h;
With ascorbate; sesamin; 2-hydroxyethanethiol In tetrahydrofuran; dimethyl sulfoxide at 28℃; Enzyme Assay General procedure: Measurement of enzyme activity was performed as follows.One hundred microliters of the reaction mixture [1 μL of 0.73 mg/mL SesA,5 μL of 1 M Tris·HCl (pH 8.0), 3 μL of 10 mM substrate (in DMSO), 10 μL of10 mM THF, and 2 μL of Tween 80 were used]. THF was dissolved in 50 mMTris·HCl (pH 9.0), 1% 2-mercaptoethanol, and 2% (wt/vol) ascorbate. Oneunit of sesamin-converting activity was defined as the amount of enzymerequired to catalyze the formation of 1 μmol of sesamin monocatechol perminute. Specific activity is expressed as units per milligram of protein.The reaction was initiated by adding the enzyme, followed by incubationat 28 °C for an appropriate time. After incubation, the reaction was stoppedby adding 100 μL of acetonitrile.
With aluminum (III) chloride In toluene at 110℃; for 24h; Chemical Synthesis of DM-PPR. PPR (4.0 mg) and 8.0 mg of anhydrousAlCl3 were placed in a 25 ml round-bottom flask and mixed with 3.0 ml oftoluene. The mixture was then refluxed at 110C for 12 hours, followed byincorporation of additional anhydrous AlCl3 (2.0 mg) and another 12 hours ofrefluxing. The resulting mixture was mixed with 0.5 ml of water after beingcooled to room temperature, and shaken well. The resulting mixture wasconcentrated under vacuum. The residue was submitted to semipreparative liquidchromatography for purification, and purified DM-PPR (Scheme 1) wascharacterized by mass spectrometry (MS) on Bruker hybrid quadrupole-timeof-flight mass spectrometer and NMR on a BRUKER-ARX-600 spectrometer(Bruker Corporation, Carteret, NJ).

Reference: [1]Venkatasamy, Radhakrishnan; Faas, Laura; Young, Antony R.; Raman, Amala; Hider, Robert C. [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 8, p. 1905 - 1920]
[2]Baruch, Yifat; Gopas, Jacob; Kadosh, Yael; Kumar, Rajendran Saravana; Kushmaro, Ariel; Muthuraman, Subramani; Yaniv, Karin [Molecules, 2021, vol. 26, # 8]
[3]Elumalai, Nagarajan; Berg, Angela; Natarajan, Kalaiselvi; Scharow, Andrej; Berg, Thorsten [Angewandte Chemie - International Edition, 2015, vol. 54, # 16, p. 4758 - 4763][Angew. Chem., 2015, vol. 127, # 16, p. 4840 - 4845,6]
[4]Berg, Angela; Berg, Thorsten; Elumalai, Nagarajan; Natarajan, Kalaiselvi; Scharow, Andrej [Angewandte Chemie - International Edition, 2015, vol. 54, # 16, p. 4758 - 4763][Angew. Chem., 2015, vol. 127, # 16, p. 4840 - 4845,6]
[5]Muthuraman, Subramani; Sinha, Shweta; Vasavi; Waidha, Kamran Manzoor; Basu, Biswarup; Munussami, Punnagai; Balamurali; Doble, Mukesh; Saravana Kumar, Rajendran [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 4, p. 604 - 619]
[6]Current Patent Assignee: KONKUK UNIVERSITY; AJOU UNIVERSITY - KR2021/57300, 2021, A Location in patent: Paragraph 0093; 0094
[7]Location in patent: scheme or table Mu, Li-Hua; Wang, Bo; Ren, Hao-Yang; Liu, Ping; Guo, Dai-Hong; Wang, Fu-Meng; Bai, Lin; Guo, Yan-Shen [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 9, p. 3343 - 3348]
[8]Kumano, Takuto; Fujiki, Etsuko; Hashimoto, Yoshiteru; Kobayashi, Michihiko [Proceedings of the National Academy of Sciences of the United States of America, 2016, vol. 113, # 32, p. 9087 - 9092]
[9]Cui, Tiantian; Peng, Ying; Tian, Xiaoxiao; Wang, Qian; Zhang, Kehan; Zheng, Jiang [Drug Metabolism and Disposition, 2020, vol. 48, # 2, p. 123 - 134]
  • 18
  • [ 94-62-2 ]
  • nigramide B [ No CAS ]
  • chabamide [ No CAS ]
  • (E)-3-(2,6-bis(benzo[d][1,3]dioxol-5-yl)-5-(piperidine-1-carbonyl)cyclohex-3-en-1-yl)-1-(piperidin-1-yl)prop-2-en-1-one [ No CAS ]
  • [(1S,5R,6R)-5-Benzo[1,3]dioxol-5-yl-6-((E)-2-benzo[1,3]dioxol-5-yl-vinyl)-2-(piperidine-1-carbonyl)-cyclohex-2-enyl]-piperidin-1-yl-methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 9% 2: 11% 3: 74% 4: 4% With rac-3-octanol; triphenylphosphine; cobalt(II) chloride at 170℃; for 72h; Further byproducts given;
1: 15% 2: 3% 3: 41% 4: 41% With rac-3-octanol; cobalt(II) chloride at 170℃; for 72h;
1: 11.5% 2: 4.2% 3: 1% 4: 11.5% With cobalt(II) chloride In various solvent(s) at 177℃; for 72h;
  • 19
  • [ 94-62-2 ]
  • (E)-3-[(1S,2S,5R,6S)-5,6-Bis-benzo[1,3]dioxol-5-yl-2-(piperidine-1-carbonyl)-cyclohex-3-enyl]-1-piperidin-1-yl-propenone [ No CAS ]
  • nigramide B [ No CAS ]
  • chabamide [ No CAS ]
  • (E)-3-(2,6-bis(benzo[d][1,3]dioxol-5-yl)-5-(piperidine-1-carbonyl)cyclohex-3-en-1-yl)-1-(piperidin-1-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 81% 2: 12% 3: 4% 4: 2% With 1,1'-bis-(diphenylphosphino)ferrocene; rac-3-octanol; cobalt(II) chloride at 170℃; for 72h; Further byproducts given;
  • 20
  • [ 736947-76-5 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
82% With aluminum oxide; potassium hydroxide; dibromodifluoromethane In dichloromethane at 20℃; for 1h;
  • 21
  • [ 58095-76-4 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: 83 percent / DIAD; Ph3P / benzene / 1 h / 20 °C 2.1: KOH / methanol / 0.17 h / 0 °C 2.2: 85 percent / methanol / 1 h / 0 °C 3.1: 92 percent / oxone / methanol; H2O / 0 °C 4.1: 82 percent / KOH; Al2O3; CBr2F2 / CH2Cl2 / 1 h / 20 °C
Multi-step reaction with 2 steps 1: 55 percent / PDC / CH2Cl2 / 20 °C 2: 90 percent / tetrahydrofuran / 24 h / Heating
Multi-step reaction with 2 steps 1: PBr3 / CH2Cl2 / 0.5 h / -5 °C 2: 1.) potassium diisopropylamide (KDA) / 1.) THF, hexane, RT, 1 h, 2.) THF, hexane, reflux
  • 22
  • [ 94-62-2 ]
  • [ 26163-80-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / KOH / ethanol / 24 h / Heating 2: 100 percent / oxalyl chloride / 0.5 h / 25 °C 3: CH2Cl2 / 1 h / 0 °C
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 113 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 24 h / 150 °C 2: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice 3: dichloromethane / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 48 h / 20 °C 2: triethylamine / dichloromethane / 45 h / 0 °C 3: triethylamine / dichloromethane / 2 h / 0 - 20 °C

  • 23
  • [ 94-62-2 ]
  • SCT-46 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / KOH / ethanol / 24 h / Heating 2: 100 percent / oxalyl chloride / 0.5 h / 25 °C 3: CH2Cl2 / 1 h / 0 °C
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 85 percent / triethylamine / tetrahydrofuran / 60 °C
  • 24
  • [ 94-62-2 ]
  • [ 4711-72-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 90 percent / KOH / ethanol / 24 h / Heating 2: 100 percent / oxalyl chloride / 0.5 h / 25 °C
Multi-step reaction with 2 steps 1: 65 percent / potassium hydroxide / ethane-1,2-diol / 180 °C 2: thionyl chloride / CH2Cl2 / 1 h / Heating
Multi-step reaction with 2 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 3 h / Reflux 2: thionyl chloride / tetrahydrofuran / 3 h / Reflux
Multi-step reaction with 2 steps 1: potassium hydroxide 2: thionyl chloride / dichloromethane / 1 h / Reflux
Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 1 h / Microwave irradiation 2: oxalyl dichloride / dichloromethane / 0.5 h / 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol / 6 h / Reflux 1.2: Cooling with ice 2.1: thionyl chloride / dichloromethane / 1 h / Reflux
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol / 24 h / 150 °C 2: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice
With thionyl chloride In dichloromethane for 1h; Reflux;
Multi-step reaction with 2 steps 1: potassium hydroxide; methanol / 48 h / Reflux 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol / 24 h / 75 °C 2: oxalyl dichloride / dichloromethane / 2 h / 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol / 24 h / 75 °C 2: oxalyl dichloride / dichloromethane / 2 h / 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 12 h / Reflux 2: thionyl chloride / dichloromethane / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 24 h / Reflux 2: thionyl chloride / dichloromethane / 7 h / 20 °C / Cooling with ice
Multi-step reaction with 2 steps 1: potassium hydroxide; methanol / 48 h / Reflux 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 16 h / 20 °C

Reference: [1]Ribeiro, Tatiana Santana; Freire-De-Lima, Leonardo; Previato, Jose Osvaldo; Mendonca-Previato, Lucia; Heise, Norton; De Lima, Marco Edilson Freire [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 13, p. 3555 - 3558]
[2]Koul, Surrinder; Koul, Jawahir L.; Taneja, Subhash C.; Dhar, Kanaya L.; Jamwal, Deshvir S.; Singh, Kuldeep; Reen, Rashmeet K.; Singh, Jaswant [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 1, p. 251 - 268]
[3]De Paula, Vanderlucia F.; De A Barbosa, Luiz C.; Demuner, Antonio J.; Pilo-Veloso, Dorila; Picanco, Marcelo C. [Pest Management Science, 2000, vol. 56, # 2, p. 168 - 174]
[4]Current Patent Assignee: UNIVERSITY OF VIENNA - WO2011/80313, 2011, A1
[5]Mu, Li-Hua; Wang, Bo; Ren, Hao-Yang; Liu, Ping; Guo, Dai-Hong; Wang, Fu-Meng; Bai, Lin; Guo, Yan-Shen [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 9, p. 3343 - 3348]
[6]Franklim, Tatiany Nunes; Freire-De-Lima, Leonardo; De Nazareth Sa Diniz, Julliana; Previato, Jose Osvaldo; Castro, Rosane Nora; Mendonca-Previato, Lucia; De Lima, Marco Edilson Freire [Molecules, 2013, vol. 18, # 6, p. 6366 - 6382]
[7]Umadevi, Parimi; Deepti, Kolli; Venugopal, Durvasula V. R. [Medicinal Chemistry Research, 2013, vol. 22, # 11, p. 5466 - 5471]
[8]Takao, Koichi; Miyashiro, Takaki; Sugita, Yoshiaki [Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 5, p. 326 - 333]
[9]Wahab, Aneela; Sultana, Amina; Khan, Khalid Mohammed; Sherwani, Sikandar K.; Perveen, Zeba; Taha, Muhammad; Karim, Aneela [Journal of the Chemical Society of Pakistan, 2015, vol. 37, # 5, p. 1008 - 1014]
[10]Hammad, Ayat S.; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar [Cell Stress and Chaperones, 2017, vol. 22, # 3, p. 417 - 428]
[11]Tantawy, Ahmed H.; Farag, Shaimaa M.; Hegazy, Lamees; Jiang, Hong; Wang, Man-Qun [Bioorganic Chemistry, 2020, vol. 94]
[12]Cao, Ruijun; Qin, Bei; Yang, Kuan [Journal of Chemistry, 2020, vol. 2020]
[13]Cao, Ruijun; Qin, Bei; Yang, Kuan [Journal of Chemistry, 2020, vol. 2020]
[14]Cui, Jian; Lee, David Yue-Wei; Liu, Jing; Liu, Tonghua; Wang, Yanli; Wu, Lili; Yao, Yuan [Drug Design, Development and Therapy, 2020, vol. 14, p. 2069 - 2078]
[15]Sivashanmugam, Arthi; Velmathi, Sivan [Chemical Biology and Drug Design, 2021, vol. 98, # 1, p. 19 - 29]
[16]Abdelazeem, Ahmed H.; Fouad, Ali; Jiang, Hong; Marzouk, Adel A.; Meng, Xiang-Gao; Tantawy, Ahmed H.; Wang, Man-Qun; Youssif, Bahaa G. M. [RSC Advances, 2021, vol. 11, # 41, p. 25738 - 25751]
  • 25
  • [ 94-62-2 ]
  • SCT-47 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / KOH / ethanol / 24 h / Heating 2: 100 percent / oxalyl chloride / 0.5 h / 25 °C 3: CH2Cl2 / 1 h / 0 °C
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 214 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 24 h / 150 °C 2: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice 3: dichloromethane / 60 °C
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Darkness; Reflux 2.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate / N,N-dimethyl-formamide; dichloromethane / 0.5 h / 0 °C 2.2: 20 °C
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Reflux 2.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate / N,N-dimethyl-formamide; dichloromethane / 0.5 h / 0 °C 2.2: 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 48 h / 20 °C 2: triethylamine / dichloromethane / 45 h / 0 °C 3: triethylamine / dichloromethane / 2 h / 0 - 20 °C

  • 26
  • [ 94-62-2 ]
  • SCT-81 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / KOH / ethanol / 24 h / Heating 2: 100 percent / oxalyl chloride / 0.5 h / 25 °C 3: CH2Cl2 / 1 h / 0 °C
Multi-step reaction with 3 steps 1: potassium hydroxide 2: thionyl chloride / dichloromethane / 1 h / Reflux 3: 0.5 h / 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 24 h / 150 °C 2: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice 3: dichloromethane / 60 °C
  • 27
  • [ 94-62-2 ]
  • [ 5950-12-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 120 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 83 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 2 steps 1: 10percent ethanolic NaOH / ethanol 2: triethylamine, methanesulfonyl chloride / 1.) CH2Cl2, 45 min., 0 deg C ; 2.) 2h, 0-25 deg C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice

  • 28
  • [ 94-62-2 ]
  • [ 25924-78-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 186 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 65 percent / potassium hydroxide / ethane-1,2-diol / 180 °C 2: thionyl chloride / CH2Cl2 / 1 h / Heating 3: 2.46 g / CH2Cl2 / 0.5 h
Multi-step reaction with 2 steps 1.1: potassium hydroxide / ethanol / 12 h / Reflux 2.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 1 h 2.2: 6 h
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 24 h / 150 °C 2: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice 3: dichloromethane / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 48 h / 20 °C 2: triethylamine / dichloromethane / 45 h / 0 °C 3: triethylamine / dichloromethane / 2 h / 0 - 20 °C

  • 29
  • [ 94-62-2 ]
  • (2E,4E)-5-(benzo[d][1,3]dioxazol-5-yl)-N-ethylpenta-2,4-dienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 156 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 60 percent / triethylamine / tetrahydrofuran / 60 °C
  • 30
  • [ 94-62-2 ]
  • (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid N-isopropylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 188 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 40 percent / triethylamine / tetrahydrofuran / 60 °C
  • 31
  • [ 94-62-2 ]
  • (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid N-(n-butyl)amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 146 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 65 percent / potassium hydroxide / ethane-1,2-diol / 180 °C 2: thionyl chloride / CH2Cl2 / 1 h / Heating 3: 4.6 g / CH2Cl2 / 0.5 h
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 69 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide 2: thionyl chloride / dichloromethane / 1 h / Reflux 3: 0.5 h / 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice

  • 32
  • [ 94-62-2 ]
  • (2E,4E)-5-Benzo[1,3]dioxol-5-yl-penta-2,4-dienoic acid hexylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 168 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 80 percent / triethylamine / tetrahydrofuran / 60 °C
  • 33
  • [ 94-62-2 ]
  • [ 263744-11-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 239 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 89 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 1 h / Reflux 2: dichloromethane / 1 h / 20 °C
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol / 24 h / Reflux 2.1: N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 2.2: 20 °C

  • 34
  • [ 94-62-2 ]
  • methyl (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 117 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide 2: sulfuric acid / 6 h / Reflux
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 16 h / Reflux 2: sulfuric acid / 16 h / Reflux
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 8 h / Reflux 2: toluene-4-sulfonic acid / 8 h / Reflux
Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 24 h / Reflux 2: thionyl chloride / dichloromethane / 7 h / 20 °C / Cooling with ice 3: triethylamine / dichloromethane / 0 - 20 °C

  • 35
  • [ 94-62-2 ]
  • all-trans-5-(3,4-Methylendioxyphenyl)-2,4-pentadiensaeureethylester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 120 mg / CH2Cl2 / 3 h / 0 - 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide 2: sulfuric acid / 6 h / Reflux
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / Reflux 2: sulfuric acid / 12 h / Reflux
Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 24 h / Reflux 2: thionyl chloride / dichloromethane / 7 h / 20 °C / Cooling with ice 3: triethylamine / dichloromethane / 0 - 20 °C

  • 36
  • [ 94-62-2 ]
  • 5-(3,4-methylenedioxy phenyl)-pentanoic acid cyclohexyl amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 60 percent / KOH / methanol / 2 h / Heating 2: Et3N / CH2Cl2 / 0.5 h / 0 °C 3: 239 mg / CH2Cl2 / 3 h / 0 - 20 °C 4: 84 percent / H2 / Pd/C / 1 h / 1551.44 Torr
  • 37
  • [ 120-57-0 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 94 percent / benzene / 24 h / Heating 2: 87 percent / DIBAL-H / tetrahydrofuran; hexane / 6 h / -10 - 20 °C 3: 55 percent / PDC / CH2Cl2 / 20 °C 4: 90 percent / tetrahydrofuran / 24 h / Heating
Multi-step reaction with 4 steps 2: 1) alkali, 2) acid 3: oxalyl chloride / benzene 4: diethyl ether
Multi-step reaction with 2 steps 1: 71 percent 2: 1.) BF3OEt2 in refluxing toluene; 2.) oxidation (m-chloroperbenzoic acid, CH2Cl2,-78 grad C); 3.) reflux in toluene
Multi-step reaction with 3 steps 1: lithium hydroxide / tetrahydrofuran / 4 h / Reflux 2: sodium hydroxide / methanol / 8 h / 20 °C 3: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 8 h / 20 °C

  • 38
  • [ 94-62-2 ]
  • [ 90670-01-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: H2 / 10 percent Pd/C / methanol / 2 h / 2585.74 Torr 2: LiAlH4 / diethyl ether / 4 h / Heating
  • 39
  • [ 94-62-2 ]
  • [ 263744-04-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 87 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide 2: thionyl chloride / dichloromethane / 1 h / Reflux 3: 0.5 h / 20 °C
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 1 h / Reflux 2: dichloromethane / 1 h / 20 °C
  • 40
  • [ 94-62-2 ]
  • 5-(3,4-methylenedioxyphenyl)-N-pentyl-2E,4E-pentadienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 45 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
  • 41
  • [ 94-62-2 ]
  • 5-(3,4-methylenedioxyphenyl)-N-[2-(2-pyridinyl)ethyl]-2E,4E-pentadienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 80 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
  • 42
  • [ 94-62-2 ]
  • (2E,4E)-5-Benzo[1,3]dioxol-5-yl-penta-2,4-dienoic acid (2-piperidin-1-yl-ethyl)-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 28 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 48 h / 20 °C 2: triethylamine / dichloromethane / 45 h / 0 °C 3: triethylamine / dichloromethane / 2 h / 0 - 20 °C
  • 43
  • [ 94-62-2 ]
  • (2E,4E)-5-(1,3-benzodioxol-5-yl)-N-adamantyl-2,4-pentadienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 68 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol / 24 h / Reflux 2.1: N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; benzotriazol-1-ol / tetrahydrofuran / 0.5 h 2.2: 20 °C
  • 44
  • [ 94-62-2 ]
  • SCT-51 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 85 percent / LiOH*H20 / ethanol; H2O / 140 h / Heating 2: oxalyl chloride / tetrahydrofuran / 6 h / 20 °C 3: 56 percent / triethylamine / tetrahydrofuran / 60 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
  • 45
  • [ 136-72-1 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: (COCl)2 / CH2Cl2 / 3 h / Ambient temperature 2: diethyl ether / 1.) -60 deg C to 10 deg C, 2.) 10 deg C, 1 h
Multi-step reaction with 2 steps 1: oxalyl chloride / benzene 2: diethyl ether
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice 2: dichloromethane / 60 °C
  • 46
  • [ 94-62-2 ]
  • [ 5950-13-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 10percent ethanolic NaOH / ethanol 2: triethylamine, methanesulfonyl chloride / 1.) CH2Cl2, 45 min., 0 deg C ; 2.) 2h, 0-25 deg C 3: H2 / 5percent Pd-C / ethanol / 3 h / 3309.8 Torr
  • 47
  • [ 110-89-4 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 2: oxidation 3: 1) n-BuLi / 1) THF, -30 deg C, 1 h, 2) -78 deg C, 0.5 h 4: pyridine 5: t-BuOK / 2-methyl-propan-2-ol / 12 h / Ambient temperature
Multi-step reaction with 2 steps 1: 98 percent / Preparation was carried out accordin to T. Nakai et al. Bull. Chem. Soc. Japan, 50, 3069 (1977), (see ref 5). 2: 1.) BF3OEt2 in refluxing toluene; 2.) oxidation (m-chloroperbenzoic acid, CH2Cl2,-78 grad C); 3.) reflux in toluene
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 8 h / 0 - 20 °C 2.1: sodium hydroxide / dimethyl sulfoxide; water / 0.5 h 2.2: 20 °C
  • 48
  • [ 425704-32-1 ]
  • [ 94-62-2 ]
  • C22H24ClN3O4 [ No CAS ]
  • C22H24ClN3O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
15.8 mg Stage #1: 5-chloro(2-nitroso)pyridine; Piperine In methanol at 21 - 60℃; for 19h; Stage #2: With hexacarbonyl molybdenum In water; acetonitrile for 6h; Heating; Further stages.;
  • 49
  • [ 1033757-04-8 ]
  • [ 94-62-2 ]
  • C22H24BrN3O4 [ No CAS ]
  • C22H24BrN3O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 5-bromo(2-nitroso)pyridine; Piperine In methanol at 21 - 60℃; for 19h; Stage #2: With hexacarbonyl molybdenum In water; acetonitrile for 6h; Heating; Further stages. Title compound not separated from byproducts.;
  • 50
  • [ 1033757-04-8 ]
  • [ 94-62-2 ]
  • (2RS,5RS)-[5-(benzo[d][1,3]dioxol-5-yl)-1-(5-bromopyridin-2-yl)-2,5-dihydro-1H-pyrrol-2-yl](piperidin-1-yl)methanone [ No CAS ]
  • (2RS,5SR)-[5-(benzo[d][1,3]dioxol-5-yl)-1-(5-bromopyridin-2-yl)-2,5-dihydro-1H-pyrrol-2-yl](piperidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 10.9 mg 2: 4.5 mg Stage #1: 5-bromo(2-nitroso)pyridine; Piperine In methanol at 21 - 60℃; for 19h; Stage #2: With hexacarbonyl molybdenum In water; acetonitrile for 6h; Heating; Stage #3: With trifluoroacetic acid In dichloromethane at 21℃; for 0.75h; Further stages.;
  • 51
  • [ 403-45-2 ]
  • [ 141-43-5 ]
  • [ 94-62-2 ]
  • 6-[6-(benzo[1,3]dioxol-5-yl)-3-(piperidin-1-ylcarbonyl)-3,6-dihydro-[1,2]oxazin-2-yl]-N-(2-hydroxyethyl)-nicotinamide [ No CAS ]
  • 6-[3-(benzo[1,3]dioxol-5-yl)-6-(piperidin-1-ylcarbonyl)-3,6-dihydro-[1,2]oxazin-2-yl]-N-(2-hydroxyethyl)-nicotinamide [ No CAS ]
  • 52
  • [ 403-45-2 ]
  • [ 94-62-2 ]
  • 6-[3-(benzo[1,3]dioxol-5-yl)-6-(piperidin-1-ylcarbonyl)-3,6-dihydro-[1,2]oxazin-2-yl]nicotinamide [ No CAS ]
  • 6-[6-(benzo[1,3]dioxol-5-yl)-3-(piperidin-1-ylcarbonyl)-3,6-dihydro-[1,2]oxazin-2-yl]nicotinamide [ No CAS ]
  • 6-[6-(benzo[1,3]dioxol-5-yl)-3-(piperidin-1-ylcarbonyl)-3,6-dihydro-[1,2]oxazin-2-yl]nicotinamide [ No CAS ]
  • 53
  • [ 94-62-2 ]
  • (6-(benzo[1,3]dioxol-5-yl)-3,6-dihydro-2H-[1,2]oxazin-3-yl)(piperidin-1-yl)methanone [ No CAS ]
  • (3-(benzo[1,3]dioxol-5-yl)-3,6-dihydro-2H-[1,2]oxazin-6-yl)(piperidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: Piperine With tetrabutylammonium periodite In dichloromethane at 21℃; for 1h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran at 21℃; for 0.5h; Further stages. Title compound not separated from byproducts.;
  • 54
  • [ 94-62-2 ]
  • (3-(benzo[1,3]dioxol-5-yl)-3,6-dihydro-2H-[1,2]oxazin-6-yl)(piperidin-1-yl)methanone [ No CAS ]
  • [ 1033756-86-3 ]
YieldReaction ConditionsOperation in experiment
1: 19% 2: 12% Stage #1: Piperine With tetrabutylammonium periodite In dichloromethane at 21℃; for 1h; Stage #2: With triethylsilane; trifluoroacetic acid In dichloromethane at 21℃; for 0.5h; Further stages.;
  • 55
  • [ 94-62-2 ]
  • [ 688035-62-3 ]
  • C23H27N3O4 [ No CAS ]
  • (Z)-5-(benzo[d][1,3]dioxol-5-yl)-5-hydroxy-2-(6-methylpyridin-2-ylamino)-1-(piperidin-1-yl)pent-3-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
47 mg Stage #1: Piperine; 2-methyl-6-nitrosopyridine In methanol at 21 - 60℃; for 19h; Stage #2: With hexacarbonyl molybdenum In water; acetonitrile for 6h; Heating; Further stages.;
  • 56
  • [ 1796-25-4 ]
  • (E)-3,4-methylenedioxycinnamaldehyde [ No CAS ]
  • [ 30511-77-4 ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
With rasta resin-PPh3-NBnEt2 In propan-1-ol at 80℃; for 24h;
  • 57
  • [ 495-86-3 ]
  • [ 94-62-2 ]
  • chabamide J [ No CAS ]
  • chabamide H [ No CAS ]
  • chabamide I [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 0.049 g 2: 0.014 g 3: 0.007 g With copper nitrate hemi(pentahydrate) In water at 100℃; for 70h; 6.8. Diels-Alder reaction of piperine (8) and fagaramide (16) To a stirred mixture of piperine (50.0 mg, 0.175 mmol), fagaramide (43 mg, 0.175 mmol), deionized water (2 mL) in a round bottom flask was added copper(II) nitrate (5 mg, 10 mol %) and refluxed for 70 h in an oil bath. After completion of the reaction, monitored by TLC (dipped in 5% w/v solution of phosphomolybdic acid in methanol and heating), the reaction mixture was cooled to room temperature and diluted with water (3 mL), extracted with EtOAc (2×5 mL), the combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuum. The residue obtained was purified by reverse phase HPLC using Phenomenex Luna C18 (250×10 mm, 10 μ), solvent system: 80% acetonitrile in water, flow rate: 1.5 mL/min, to give pure adducts (1) 0.049 g, (2) 0.014 g, and (5) 0.007 g. The structure of adduct 5 was established by spectroscopic methods (NMR, MS, and IR), whose data is identical with chabamide.6
  • 58
  • [ 94-62-2 ]
  • [ 1263201-24-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: methanol; potassium hydroxide / 6 h / Reflux 2: boric acid / toluene / 4 h / Reflux
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 24 h / 75 °C 2: oxalyl dichloride / dichloromethane / 2 h / 20 °C 3: triethylamine / dichloromethane / 4 h / 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 12 h / Reflux 2: thionyl chloride / dichloromethane / Reflux; Inert atmosphere 3: triethylamine / dichloromethane / 2 h / 20 °C / Cooling with ice
  • 59
  • [ 376587-49-4 ]
  • [ 94-62-2 ]
  • 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
  • 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 14% 2: 8% Stage #1: (11R)-11-carbomethoxy-11-methoxycarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene With lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 0℃; for 2h; Inert atmosphere; Stage #2: Piperine In tetrahydrofuran; hexane at -78 - 20℃; for 72h; Inert atmosphere; 4.2. General procedure for the synthesis of 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracenes (+/-)-5 and (+/-)-6 General procedure: To a 250 mL round-bottomed flask equipped with a magnetic stirrer fitted with a three-way stopcock with a septum cap and nitrogen inlet were added THF (50 mL) and dry diisopropylamine (7.9 mL, 55.97 mmol) via syringes. The mixture was cooled down to -78 °C, after which n-butyllithium (1.4 M in hexane, 33.0 mL, 46.64 mmol) was added and the mixture left to stir at 0 °C for 1 h. A solution of (+/-)-dimethyl itaconate-anthracene adduct (+/-)-2 (13.1 g, 38.9 mmol) in THF (50 mL) was introduced to the LDA solution at -78 °C, then the mixture was stirred at 0 °C for 2 h. A solution of piperine 1 (13.3094 g, 46.6 mmol) in THF (100 mL) was added to the anion solution at -78 °C after which the reaction mixture was left to stir at room temperature for 3 days. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution at 0 °C and the crude mixture was extracted several times with CH2Cl2. The dichloromethane solution was washed with H2O, a saturated NaCl solution, then dried over MgSO4, filtered and evaporated to dryness. The crude product was purified by flash column chromatography (silica gel) using EtOAc/CH2Cl2/hexane = 2:0.5:7.5 as eluent to give the diastereoisomeric spirocyclopentanone-anthracene adducts, 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclo pentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracenes (+/-)-5 and (+/-)-6 in 23% (2.37 g), and 15% (1.55 g) respectively.
  • 60
  • [ 376587-48-3 ]
  • [ 94-62-2 ]
  • 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
  • 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 33% 2: 17% Stage #1: (11S)-11-carbomethoxy-11-methoxycarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene With lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 0℃; for 2h; Inert atmosphere; Stage #2: Piperine In tetrahydrofuran; hexane at -78 - 20℃; for 72h; Inert atmosphere; 4.2. General procedure for the synthesis of 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracenes (+/-)-5 and (+/-)-6 General procedure: To a 250 mL round-bottomed flask equipped with a magnetic stirrer fitted with a three-way stopcock with a septum cap and nitrogen inlet were added THF (50 mL) and dry diisopropylamine (7.9 mL, 55.97 mmol) via syringes. The mixture was cooled down to -78 °C, after which n-butyllithium (1.4 M in hexane, 33.0 mL, 46.64 mmol) was added and the mixture left to stir at 0 °C for 1 h. A solution of (+/-)-dimethyl itaconate-anthracene adduct (+/-)-2 (13.1 g, 38.9 mmol) in THF (50 mL) was introduced to the LDA solution at -78 °C, then the mixture was stirred at 0 °C for 2 h. A solution of piperine 1 (13.3094 g, 46.6 mmol) in THF (100 mL) was added to the anion solution at -78 °C after which the reaction mixture was left to stir at room temperature for 3 days. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution at 0 °C and the crude mixture was extracted several times with CH2Cl2. The dichloromethane solution was washed with H2O, a saturated NaCl solution, then dried over MgSO4, filtered and evaporated to dryness. The crude product was purified by flash column chromatography (silica gel) using EtOAc/CH2Cl2/hexane = 2:0.5:7.5 as eluent to give the diastereoisomeric spirocyclopentanone-anthracene adducts, 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclo pentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracenes (+/-)-5 and (+/-)-6 in 23% (2.37 g), and 15% (1.55 g) respectively.
  • 61
  • 11-carbomethoxy-11-methoxycarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
  • [ 94-62-2 ]
  • 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
  • 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracene [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 23% 2: 15% Stage #1: 11-carbomethoxy-11-methoxycarbonylmethyl-9,10-dihydro-9,10-ethanoanthracene With lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 0℃; for 2h; Inert atmosphere; Stage #2: Piperine In tetrahydrofuran; hexane at -78 - 20℃; for 72h; Inert atmosphere; 4.2. General procedure for the synthesis of 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclopentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracenes (+/-)-5 and (+/-)-6 To a 250 mL round-bottomed flask equipped with a magnetic stirrer fitted with a three-way stopcock with a septum cap and nitrogen inlet were added THF (50 mL) and dry diisopropylamine (7.9 mL, 55.97 mmol) via syringes. The mixture was cooled down to -78 °C, after which n-butyllithium (1.4 M in hexane, 33.0 mL, 46.64 mmol) was added and the mixture left to stir at 0 °C for 1 h. A solution of (+/-)-dimethyl itaconate-anthracene adduct (+/-)-2 (13.1 g, 38.9 mmol) in THF (50 mL) was introduced to the LDA solution at -78 °C, then the mixture was stirred at 0 °C for 2 h. A solution of piperine 1 (13.3094 g, 46.6 mmol) in THF (100 mL) was added to the anion solution at -78 °C after which the reaction mixture was left to stir at room temperature for 3 days. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution at 0 °C and the crude mixture was extracted several times with CH2Cl2. The dichloromethane solution was washed with H2O, a saturated NaCl solution, then dried over MgSO4, filtered and evaporated to dryness. The crude product was purified by flash column chromatography (silica gel) using EtOAc/CH2Cl2/hexane = 2:0.5:7.5 as eluent to give the diastereoisomeric spirocyclopentanone-anthracene adducts, 4'-((E)-2-(benzo[c][1,3]dioxol-1-yl)vinyl)-3'-methoxycarbonyl-5'-(piperidine-1-carbonyl)cyclo pentanone-2'-spiro-11-9,10-dihydro-9,10-ethanoanthracenes (+/-)-5 and (+/-)-6 in 23% (2.37 g), and 15% (1.55 g) respectively.
  • 62
  • [ 94-62-2 ]
  • chabamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With silica gel In neat (no solvent, solid phase) at 200℃; for 3h; regioselective reaction;
  • 63
  • [ 94-62-2 ]
  • [ 161196-20-9 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide In ethanol Reflux; 1; 11 Example 1 Method 1 for preparing sodium piperonyl pentadienoate (GB-Na). Example 1 Method 1 for preparing sodium piperonyl pentadienoate (GB-Na). See the process flow chart showed in Fig. l l . Piperonyl pentadiene cyclohexylamide (piperine, GB-O) was dissolved into ethanol, and KOH was added. Then, the mixture was heated and refluxed for 6-16 hours. The mixture then was cooled, left to stand, and filtrated under vacuum, to yield potassium piperonyl pentadienoate (potassium piperonylate, GB-K) as crystal. The potassium piperonyl pentadienoate was dissolved into water, acidified with sulfuric acid to produce piperonyl pentadienoic acid (piperonylic acid, GB-H) as precipitate, filtrated under vacuum. The piperonyl pentadienoic acid was dissolved into hot ethanol. The solution of sodium hydroxide in ethanol was added to the hot solution, to yield sodium piperonyl pentadienoate (sodium piperonylate, GB-Na) as precipitate. The mixture was cooled to room temperature, and filtrated under vacuum. The precipitate GB-Na was washed with anhydrous ethanol for three times, filtrated under vacuum, and dried, to obtain GB-Na as pale yellow solid. The formula of GB-Na: Ci2H9Na04; ESI-MS m/z: 217.0 [M-Na]". The specific reaction conditions are as follows: Piperonylic Amount of Amount of Reaction Reaction Output of Yield of acid (g) ethanol (ml) NaOH (g) time (h) temperature( sodium sodium salt °C) salt (g) (%) 1 7.8 0.184 1 80 1.053 95.61 2 15.6 0.367 1 81 2.108 95.73 5 39 0.917 1 80 5.276 95.85 10 78 1.84 1 81 10.49 95.31 20 156 3.67 1 80 21.02 95.49 40 312 7.37 1 80.5 42.11 95.63 80 624 14.7 1 79 84.37 95.80 150 1170 27.6 1 81 159.0 96.29 300 2340 55.1 1 80.5 318.4 96.41 2000 15600 368 1.5 81 2120.3 96.30 The structure determination of sodium piperonyl pentadienoate (GB- Na) 500 MHz JH-NMR (see Fig. la) spectrum and 125 MHz 13C-NMR nuclear magnetic resonnance spectrum (see Fig. lb) of sodium piperonyl pentadienoate (GB-Na) were determined using 500 MHz Bruker NMR spectrometer and deuterium oxide as a solvent. Table of ^-NMR spectrum chemical shift data for sodium piperonyl pentadienoate, unit (ppm) Table of 13C-NMR spectrum chemical shift data for sodium piperonyl pentadienoate, unit (ppm) C-5 140.40 C-l l 125.28 C-6 133.77 C-12 104.02
With potassium hydroxide In ethanol for 8h; Reflux; Further stages; 1 Example 1 Example 1, the pharmaceutical compound pepper acid hexamethylene diamine is characterized by the following structure: Preparation of the said pharmaceutical compound pepper acid hexamethylene diamine in claim 1 comprises of the following steps: (1) Preparation of potasium pepper acid: first pour 95% ethanol into a double glass reactor, add solid KOH with stirring to dissolve, add heat, then put piperine solid into the reactor, continue adding heat under reflux for 8 hours. After completion of reaction, cool reaction system to room temperature for 15 hours. Withdraw supernatant. Use 95% ethanol to wash. Make PH = 7-8 to remove supernatant and obtain pepper acid potassium salt; (2)Preparation of pepper acid: dissolve pepper acid potassium salt with deionized water to produce a brown-yellow transparent solution. On the top, add dropwise hydrochloric acid solution with hydrochloric acid:water (Hcl:H2O) volumetric ratio of 1:1. adjust pH of the solution to PH=1-2. At this time, separate out pepper acid yellow solid. Place precipitate, remove supernatant; wash with deionized water until PH=6-7, vacuum filtration. At 100 and below, dry for 24 hours; (3)Preparaion of pepper acid ethyl ester: first pour anhydrous ethanol into a reactor, add dropwise concentrated sulfuric acid with stirring, openings make its heat (note: not sure), add pepper acid, install condenser and thermometer, heat under reflux for 8h, add reactants while hot into a saturated Na2CO3 solution, add deionized water to dissolve suspended matters, cool, use distilled water to wash, filter under vacuum, dry at 50. (4)Preparation of pepper acid hexamethylene diamine: first pour anhydrous ethanol into a reactor. Under stirring: add catalyst metallic sodium and after it completely dissolves, add hexamethylene diamine as well as pepper acid ethyl ester. Install condenser and thermometer. Under nitrogen gas protection, gradually increase reaction temperature to 65-70. use TLC tracking and monitoring device and continue reflux for 48 hours. After completion of reaction, a white precipitate appeared in the solution. After sufficiently cooling the reaction solution, filter to remove solid. Obtaind filtrate was added to distilled water. At this time, a large amount of white precipitate can be seen in the solutio. After stirring for 3h, filter and retain solid. After drying, obtain crude product. Use a solvent mixture of ethyl acetate and n-hexane in a 1:1 volumetric ratio to wash purely and dry. Then, recrystallize to give a white solid, pepper acid hexamethylene diamine.
Multi-step reaction with 2 steps 1.1: potassium hydroxide / ethanol / 20 h / Reflux 1.2: pH 3 2.1: potassium hydroxide / ethanol / 1 h / 20 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 20 h / Reflux 2: potassium hydroxide / ethanol / 1 h / 20 °C
5 g With potassium hydroxide In ethanol for 20h; Potassium piperate (7) In a 100 mL flask, 6.0 g (0.021 mol) of piperine wassuspended in 60 mL of 20% KOH alcoholic solution. Thereaction mixture was kept under reflux and stirring for 20 h.After completion of the reaction, the mixture was filtered,washed with ethanol, and dried, and 5.0 g (92.9%) of abrown granular solid was obtained. 1H NMR (400 MHz,D2O) d 7.05 (dd, J 15.5, 9.6 Hz, 1H, =C-H), 6.86 (d,J 1.6 Hz, 1H, C-HAr), 6.82 (dd, J 8.2, 1.6 Hz, 1H, C-HAr),6.73 (d, J 8.0 Hz, 1H, C-HAr), 6.60 (m, 2H, =C-H), 5.92(d, J 15.2 Hz, 1H, =C-H), 5.88 (s, 2H, O-CH2-O).

Reference: [1]Current Patent Assignee: BORIJIHAN GERILEITU; INNER MONGOLIA UNIVERSITY - WO2013/78983, 2013, A1 Location in patent: Page/Page column 10-12
[2]Current Patent Assignee: Tursunbek, Yerda - CN105348250, 2016, A Location in patent: Paragraph 0010; 0011; 0012; 0013
[3]Abrantes, Renata Albuquerque de; Athayde-Filho, Petrônio Filgueiras de; Batista, Tatianne Mota; Brandão, Maria Cláudia Rodrigues; Cavalcanti, Raquel Fragoso Pereira; Duarte, Sâmia Sousa; Farias, Davi Felipe; Ferreira, Rafael Carlos; Leite, Fagner Carvalho; Lisboa, Thaís Mangeon Honorato; Mangueira, Vivianne Mendes; Medeiros, Karina Carla de Paula; Silva, Daiana Karla Frade; Sobral, Marianna Vieira; Sousa, Tatyanna Kélvia Gomes de; Trindade, Emmely Oliveira da [Biomedicine and Pharmacotherapy, 2020, vol. 128]
[4]Barbosa-Filho, José M.; Brandão, Maria Cláudia R.; Lima, Edeltrudes O.; Lira, Bruno F.; Neto, Hermes D.; Souza, Helivaldo D. S.; Trindade, Emmely O.; de Athayde-Filho, Petrônio F. [Journal of the Brazilian Chemical Society, 2020, vol. 31, # 8, p. 1668 - 1678] Barbosa-Filho, José M.; Brandao, Maria C. R.; De Athayde-Filho, Petrônio F.; Dutra, Thalisson F.; Lima, Edeltrudes O.; Lira, Bruno F.; Neto, Hermes Diniz; Trindade, Emmely O. [Journal of the Brazilian Chemical Society, 2020, vol. 31, # 12, p. 2590 - 2602]
[5]Souza, Joselito S.; Martins, Evandro P.S.; Souza, Helivaldo D.S.; de Oliveira, Rafael F.; Alves, Francinara S.; Lima, Edeltrudes O.; Cordeiro, Laísa V.; Trindade, Emmely O.; Lira, Bruno F.; Rocha, Gerd B.; de Athayde-Filho, Petronio F.; Barbosa-Filho, José M. [Journal of the Brazilian Chemical Society, 2021, vol. 32, # 3, p. 490 - 502]
  • 64
  • [ 94-62-2 ]
  • [ 161196-18-5 ]
YieldReaction ConditionsOperation in experiment
70.03% With sodium hydroxide In ethanol at 86.5℃; for 24h; 2 Example 2 Method 2 for preparing sodium piperonyl pentadienoate (GB-Na). Example 2 Method 2 for preparing sodium piperonyl pentadienoate (GB-Na). The piperine and a certain amount of NaOH were dissolved into ethanol. The mixture was heated and refluxed for 16-26 hours, cooled and left to stand, to yield hydrolyzate as crystal. The crystal was washed with ethanol until becoming neutral, dried under vacuum, to obtain pale yellow solid (sodium piperonyl pentadienoate, GB-Na). The formula of GB-Na: Ci2H9Na04; ESI-MS m/z: 217.0 [M-Na]". The specific reaction conditions are as follows: Piperine Amount of Amount of Reaction Reaction Output of Yield of (g) ethanol (ml) NaOH (g) time (h) temperatur sodium salt(g) sodium salt e (°C) (%) 1 7.8 2.11 24 86 0.585 69.51 5 39 10.56 24 86.5 2.949 70.03 10 78 21.14 24 86 5.871 69.72 The structure determination of sodium piperonyl pentadienoate (GB- Na) 500 MHz JH-NMR (see Fig.2a) spectrum and 125 MHz 13C-NMR nuclear magnetic resonance spectrum (see Fig.2b) of sodium piperonyl pentadienoate (GB-Na) were determined using a 500 MHz Bruker NMR spectrometer and deuterium oxide as a solvent. Table of ^-NMR spectrum chemical shift data for sodium piperonyl pentadienoate, unit (ppm) H-12 5.970 Table of 13C-NMR spectrum chemical shift data for sodium piperonyl pentadienoate, unit (ppm)
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / Reflux 2: sulfuric acid / water monomer 3: sodium hydroxide / ethanol / 1 h / 80.5 °C
With potassium hydroxide In methanol at 80℃; for 72h;
  • 65
  • [ 94-62-2 ]
  • [ 1451149-80-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 1 h / Microwave irradiation 2: oxalyl dichloride / dichloromethane / 0.5 h / 20 °C / Inert atmosphere 3: hydrazine hydrate / dichloromethane / 0.5 h / 20 °C / Cooling with ice
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / Reflux 2: sulfuric acid / 12 h / Reflux 3: hydrazine hydrate / 4 h / Reflux
Multi-step reaction with 3 steps 1: potassium hydroxide; methanol / 48 h / Reflux 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 20 °C 3: hydrazine / dichloromethane / 7 h / 20 °C
  • 66
  • 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one [ No CAS ]
  • [ 94-62-2 ]
  • [ 1596306-45-4 ]
YieldReaction ConditionsOperation in experiment
30% With acetonitrile In dichloromethane at 80℃; for 16h;
  • 68
  • [ 94-62-2 ]
  • 4-(5-oxo-5-(piperidin-1-yl)pentyl)-1,2-phenylene bis(dihydrogen phosphate) [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: boron tribromide / dichloromethane / 16 h / 0 - 20 °C 2: tetrachloromethane; N-ethyl-N,N-diisopropylamine; dmap / acetonitrile / 0 °C 3: palladium 10% on activated carbon; hydrogen / ethanol
Multi-step reaction with 3 steps 1: boron tribromide / dichloromethane / 16 h / 0 - 20 °C 2: tetrachloromethane; dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 0 °C 3: palladium 10% on activated carbon; hydrogen / ethanol
  • 69
  • [ 110-89-4 ]
  • (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienamide [ No CAS ]
  • [ 94-62-2 ]
YieldReaction ConditionsOperation in experiment
83% With dipotassium peroxodisulfate In water at 100℃; for 0.166667h; Microwave irradiation; Green chemistry; General procedure for microwave reaction General procedure: Amide (1.0 mmol), amine (1.0 mmol) and K2S2O8 (1.5 mmol) were charged in microwave vial added water (2.0 mL), the reaction mixture was treated at 100°C and 100W for 10 min. After the complete conversion (by TLC) of the amine, distilled water (10 mL) was added and extracted with ethyl acetate (2 ×10 mL). The combined organic phase was dried over Na2SO4, and then concentrated using rotary vacuum evaporator. The crude product was purified by column chromatography (30% Ethyl acetate/hexane) to get pure compound.
  • 70
  • [ 94-62-2 ]
  • (2E,4E)-5-(benzo[d] [1,3]dioxol-5-yl)-N-phenethylpenta-2,4-dienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 22 h / Reflux 2: oxalyl dichloride / dichloromethane / 3 h / 20 °C 3: triethylamine / 5 h / 20 °C / Cooling with ice
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Reflux 2.1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate / N,N-dimethyl-formamide; dichloromethane / 0.5 h / 0 °C 2.2: 20 °C
  • 71
  • [ 94-62-2 ]
  • [ 1087058-28-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium hydroxide / methanol / 24 h / 150 °C 2: thionyl chloride / dichloromethane / 2 h / Inert atmosphere; Cooling with ice 3: dichloromethane / 60 °C
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Darkness; Reflux 2.1: N-ethyl-N,N-diisopropylamine; benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate / N,N-dimethyl-formamide; dichloromethane / 0.5 h / 0 °C 2.2: 20 °C
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Reflux 2.1: N-ethyl-N,N-diisopropylamine; benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate / N,N-dimethyl-formamide; dichloromethane / 0.5 h / 0 °C 2.2: 20 °C
Multi-step reaction with 3 steps 1: potassium hydroxide; ethanol / Reflux 2: triethylamine / propan-2-one / 0.5 h / 0 °C 3: propan-2-one / 0 - 20 °C
Multi-step reaction with 2 steps 1.1: potassium hydroxide / methanol / 24 h / Reflux; Inert atmosphere 2.1: N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; benzotriazol-1-ol / tetrahydrofuran / 0.5 h / 0 °C / Inert atmosphere 2.2: 16 h / 20 °C / Inert atmosphere

  • 72
  • [ 94-62-2 ]
  • (3E,5E)-6-(benzo[d][1,3]dioxol-5-yl)-2-(piperidin-1-yl)hexa-3,5-dienenitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% Stage #1: Piperine With bis(triphenylphosphine)iridium(I) carbonyl chloride In toluene at 20℃; for 0.0833333h; Stage #2: With 1,1,3,3-Tetramethyldisiloxane In toluene at 20℃; for 0.0833333h; Stage #3: With trimethylsilyl cyanide In toluene at 20℃; for 0.5h;
  • 73
  • [ 501-36-0 ]
  • [ 94-62-2 ]
  • 2C17H19NO3*C14H12O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With Parafilm In acetone; acetonitrile at 4℃; for 216h;
  • 74
  • [ 94-62-2 ]
  • phenyl (2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)penta-2,4-dienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Darkness; Reflux 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 0.5 h / 20 °C 2.2: Darkness
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 24 h / Reflux 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 0.5 h / 20 °C 2.2: 20 °C / Darkness
Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 24 h / Reflux 2: thionyl chloride / dichloromethane / 7 h / 20 °C / Cooling with ice 3: triethylamine / dichloromethane / 0 - 20 °C
  • 75
  • N-benzyl C-(trifluoromethyl)nitrone [ No CAS ]
  • [ 94-62-2 ]
  • 5-(((E)-2-(benzo[d][1,3]dioxol-5-yl)vinyl)-2-benzyl-3-(trifluoromethyl)isoxazolidin-4-yl)(piperidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% In toluene at 70 - 80℃; chemoselective reaction;
  • 76
  • [ 2344-50-5 ]
  • [ 94-62-2 ]
  • 5-(((E)-2-(benzo[d][1,3]dioxol-5-yl)vinyl)-tert-butyl-3-(trifluoromethyl)isoxazolidin-4-yl)(piperidin-1-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% In toluene at 70 - 80℃; chemoselective reaction;
  • 78
  • [ 94-62-2 ]
  • 4S,5S-dihydroxypiperine [ No CAS ]
YieldReaction ConditionsOperation in experiment
44.4% Stage #1: Piperine With potassium osmate(VI) dihydrate; (DHQD)<SUB>2</SUB>PHAL; potassium carbonate; potassium hexacyanoferrate(III) In water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Stage #2: With sodium sulfite In water; <i>tert</i>-butyl alcohol at 20℃; for 12h; 2 Example 2 Preparation of 4S,5S-dihydroxypiperine (compound 2): Take 5mL water and 5mL tert-butanol,Stir well as a solvent. Add potassium ferricyanide (807.7mg, 2.45mmol) to the mixed solvent,Potassium carbonate (339.1mg, 2.45mmol),Potassium osmate dihydrate (1.3mg, 3.5μmol), (DHQD) 2PHAL (5.4mg, 0.701mmol)After reacting at room temperature for 20 min, piperine (200 mg, 0.701 mmol) was added, and the mixture was stirred at room temperature for 24 h. Anhydrous sodium sulfite (1.5443 mg, 12.3 mmol) was added to the mixture and stirred at room temperature for 12 h.Add the reaction solution to 25mL of water,It was extracted with ethyl acetate (25×3 mL), and the combined organic phases were concentrated in vacuo to obtain a crude product. The crude product obtained was purified by flash column chromatography (silica gel, DCM:MeOH=35:1),Get the corresponding 4S,5S-dihydroxypiperine,It is a transparent oil, and the yield is 44.4% (99.4mg);
44.4% With potassium osmate(VI) dihydrate; potassium carbonate; hydroquinidein 1,4-phthalazinediyl diether; potassium hexacyanoferrate(III) In water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Synthesis of compound 2 Potassium ferricyanide (807.7 mg, 2.45 mmol), potassium carbonate(339.1 mg, 2.45 mmol), potassium osmate dihydrate (1.3 mg, 3.5 mol),(DHQD)2PHAL (5.4 mg, 0.701 mmol) were added to a dry roundbottomedflask (25 mL) and dissolve in a mixture of water (5 mL) andtert-butanol (5 mL). The solvent was allowed to stir at room temperaturefor 20 min. Piperine (200 mg, 0.701 mmol) was then added and stirredat room temperature for 24 h. Then anhydrous sodium sulfite (1.55 g,12.3 mmol) was added and stirred at room temperature for 12 h. Water(25 mL) was added and the mixture was extracted with ethyl acetate (25mL × 3). The organic phase was collected, filtered and concentrated.The crude residue was purified by flash column chromatography onsilica gel using dichloromethane/methanol (DCM:MeOH = 35:1) aseluent to afford the desired compound 2 (99.4 mg, 44.4%).
  • 79
  • [ 94-62-2 ]
  • 4R,5R-dihydroxypiperine [ No CAS ]
YieldReaction ConditionsOperation in experiment
44.5% Stage #1: Piperine With potassium osmate(VI) dihydrate; (DHQ)<SUB>2</SUB>PHAL; potassium carbonate; potassium hexacyanoferrate(III) In water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Stage #2: With sodium sulfite In water; <i>tert</i>-butyl alcohol at 20℃; for 12h; 1 Example 14R,5R-dihydroxyPiperine(Compound 1) Preparation: Take 5mL water and 5mL tert-butanol,Stir well as a solvent. Add potassium ferricyanide (807.7mg, 2.45mmol) to the mixed solvent,Potassium carbonate (339.1mg, 2.45mmol),Potassium osmate dihydrate (1.3mg, 3.5μmol), (DHQ)2PHAL (5.4mg, 0.701mmol) were reacted at room temperature for 20min, then piperine (200mg, 0.701mmol) was added, and the mixture was stirred at room temperature for 24h. Add anhydrous sodium sulfite (1.5443mg, 12.3mmol) to the mixture and stir at room temperature for 12h,Stop the reaction. Add the reaction solution to 25mL of water,It was extracted with ethyl acetate (25×3 mL), and the combined organic phases were concentrated in vacuo to obtain a crude product. The crude product obtained was purified by flash column chromatography (silica gel, DCM:MeOH=35:1),Get the corresponding 4R,5R-dihydroxypiperine,It is a transparent oil with a yield of 44.5% (99.8mg);
44.5% With potassium osmate(VI) dihydrate; potassium carbonate; hydroquinidein 1,4-phthalazinediyl diether; potassium hexacyanoferrate(III) In water; <i>tert</i>-butyl alcohol at 20℃; for 24h; Synthesis of compound 1 Potassium ferricyanide (807.7 mg, 2.45 mmol), potassium carbonate(339.1 mg, 2.45 mmol), potassium osmate dihydrate (1.3 mg, 3.5 mol),and (DHQ)2PHAL (5.4 mg, 0.701 mmol) were added to a dry roundbottomedflask (25 mL) and dissolve in a mixture of water (5 mL) andtert-butanol (5 mL). The solvent was allowed to stir at room temperaturefor 20 min. Piperine (200 mg, 0.701 mmol) was then added, and stirredat room temperature for 24 h. Then anhydrous sodium sulfite (1.55 g, 12.3 mmol) was added and stirred at room temperature for 12 h. Water(25 mL) was added and the mixture was extracted with ethyl acetate (25mL × 3). The organic phase was collected, filtered and concentrated.The crude residue was purified by flash column chromatography onsilica gel using dichloromethane/methanol (DCM:MeOH = 35:1) elutionto afford compound 1 (99.8 mg, 44.5%).
  • 80
  • [ 94-62-2 ]
  • (2Z,4Z)-3,5-diamino-5-(benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% Stage #1: Piperine With sulfur In dimethyl sulfoxide at 20℃; Sealed tube; Stage #2: With ammonium carbonate In dimethyl sulfoxide at 80℃; for 12h; Sealed tube;
  • 81
  • [ 94-62-2 ]
  • dibenzyl 4-((1E,3E)-5-oxo-5-(piperidin-1-yl)penta-1,3-dienyl)-1,2-phenylene diphosphate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: boron tribromide / dichloromethane / 16 h / 0 - 20 °C 2: tetrachloromethane; dmap; N-ethyl-N,N-diisopropylamine / acetonitrile / 0 °C
  • 82
  • [ 51-61-6 ]
  • [ 94-62-2 ]
  • N-[2-(3,4-dihydroxyphenyl)ethyl]-5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With chloro-trimethyl-silane; 1,10-Phenanthroline; tungsten(VI) chloride In 1-methyl-pyrrolidin-2-one at 140℃; for 36h;
  • 83
  • [ 142-84-7 ]
  • [ 94-62-2 ]
  • [ 1313740-79-2 ]
YieldReaction ConditionsOperation in experiment
48% With chloro-trimethyl-silane; 1,10-Phenanthroline; tungsten(VI) chloride In 1-methyl-pyrrolidin-2-one at 140℃; for 36h;
  • 84
  • [ 94-62-2 ]
  • [ 30511-77-4 ]
YieldReaction ConditionsOperation in experiment
41% Stage #1: Piperine With 3F6P(1-)*C108H78Ir3N12(3+) In dichloromethane-d2 at 20℃; for 0.333333h; Inert atmosphere; Sealed tube; Darkness; Stage #2: In dichloromethane-d2 at 20℃; for 0.5h; Inert atmosphere; Sealed tube; Darkness; Irradiation;
  • 85
  • [ 109522-62-5 ]
  • [ 94-62-2 ]
  • ethyl (4E,6E)-7-(benzo[d][1,3]dioxol-5-yl)-2,2-difluoro-3-(piperidin-1-yl)hepta-4,6-dienoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% Stage #1: Piperine With bis(triphenylphosphine)iridium(I) carbonyl chloride; 1,1,3,3-Tetramethyldisiloxane In toluene at 20℃; for 1h; Inert atmosphere; Stage #2: (2-ethoxy-1,1-difluoro-2-oxoethyl)zinc(II) bromide In toluene at 0 - 20℃; for 0.333333h; Inert atmosphere;
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