Name: 10500-57-9|5,6,7,8-Tetrahydroquinoline|97%
Brand: Ambeed
SKU: A371016
Price: 5.0 USD
Availability: InStock
Rating: 97 (30 reviews)

2
[ 21172-88-3 ]
[ 10500-57-9 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1930,vol. 478,p. 176,195
[2]Justus Liebigs Annalen der Chemie,1930,vol. 478,p. 176,195

3
[ 858279-01-3 ]
[ 10500-57-9 ]

Reference： [1]Helvetica Chimica Acta,1945,vol. 28,p. 1684,1690

4
[ 91-22-5 ]
[ 10500-57-9 ]
[ 635-46-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 92% 2: 7%	With 5% Ru/MgO; hydrogen In tetrahydrofuran at 150℃; for 0.7h;
1: 6% 2: 80%	With hydrogen In trifluoroacetic acid
1: 58% 2: 14%	With Cp*Rh(2-(2-pyridyl)phenyl)H; hydrogen In tetrahydrofuran at 80℃; for 48h; Glovebox;

1: 42% 2: 5%	With potassium hydroxide; hydrogen In tetrahydrofuran at 180℃; for 2h; other reagents, catalysts, temperature, time;
	With platinum; hydrogen In water at 80℃; for 24h; Schlenk technique; Sealed tube;
	With 5% active carbon-supported ruthenium; hydrogen In water at 60℃; for 15h; Autoclave; chemoselective reaction;
	With [1-butyl-2,3-dimethylimidazolium][tppm] stabilized rhodium nanoarticles at 50℃; for 5h; Ionic liquid; Autoclave; Overall yield = 75.5 %; chemoselective reaction;	General procedure for the heterogeneous selective hydrogenation General procedure: The stainless steel autoclave containing previously prepared PFIL-stabilized Rh(0) catalysts was charged with the appropriate substrate, then the autoclave was sealed and purged with pure hydrogen several times. After the reactants were heated to predetermined temperature, the reaction timing began. After completion of the reaction and cooling to ambient temperature, the products were isolated by liquid-liquid extraction with diethylether and analyzed by gas chromatography.
	With 6C₅₃H₃₂O₈^(4-)13Zr⁽⁴⁺⁾18O^(2-)8Co⁽²⁺⁾8H^(1-); hydrogen In tetrahydrofuran at 80℃; for 48h; Overall yield = 95 %Spectr.;
1: 88 %Spectr. 2: 10 %Spectr.	With ruthenium; hydrogen; 1-butyl-2,3-dimethylimidazolium bis-(trifluoromethanesulfonyl)amide; butan-1-ol at 80℃; for 5h; Autoclave;
	With hydrogen In tetrahydrofuran at 99.84℃; for 4h; Autoclave; regioselective reaction;
	With hydrogen In methanol at 80℃; for 4h; Autoclave;	2.5. General procedure for the selective hydrogenation of quinolinecompounds General procedure: Typically, 1.0 mmol of quinoline compounds, 6 mL of solvent and acertain amount of PdCIL-T catalyst were added into a 50 mL PTFEreaction vessel or thick walled pressure vessel. The mixture was stirredfor 2 min to ensure complete dispersion of the catalyst and then placedin a 50 mL stainless-steel autoclave. After being flushed three timeswith H2, the pressure was elevated to 1-10 atm at room temperature.The autoclave was then heated to 30-120 °C with a magnetic stir for acertain time. Subsequently, the catalyst was removed from the mixtureby centrifugation, and the liquid sample was analyzed by GC or GC-MS.The calculations of conversion and selectivity were based on the followingformula: Conversion=[consumed substrate]/[initial substrate]×100%, Selectivity=[py-THQs]/[all hydrogenated products]×100%.
	With 6C₅₃H₃₂O₈^(4-)13Zr⁽⁴⁺⁾18O^(2-)8Co⁽²⁺⁾8Cl^(1-); hydrogen; sodium triethylborohydride In toluene at 80℃; for 48h; Overall yield = 95 %Spectr.;	16 Example 16 Catalytic Hydrogenation of Heterocycles with Zr-MTBC-CoH General procedure: At a 0.5 mol % Co loading, Zr-MTBC-CoH catalyzed hydrogenation of indole in toluene at 80° C. to afford a mixture of indoline and 4,5,6,7-tetrahydroindole. Indoline was obtained in 84% isolated yield after preparative TLC. See first entry, Table 19, below. Hydrogenation of 3-methyl-indole gave 3-methyl-indoline and 3-methyl-4,5,6,7-tetrahydroindole in 46:54 ratio, which indicates that reduction of the phenyl ring is also possible. Hydrogenation of quinolines in toluene at 80° C. gave a mixture of two products, 1,2,3,4-tetrahydroquinoline and 5,6,7,8-tetrahydro-quinoline in a 1:1 ratio. Under identical reaction conditions, the selectivity appears dependent on the substitution of the phenyl ring. Electron-donating substituents at the 6-position of the quinolines favor the hydrogenation of the phenyl ring. For example, the 6-methylquinoline, 6-methoxyquinoline and 2,6-dimethylquinoline were hydrogenated to give 6-methyl-5,6,7,8-tetrahydro-quinoline, 6-methoxy-5,6,7,8-tetrahydro-quinoline and 2,6-dimethyl-5,6,7,8-tetrahydro-quinoline, respectively, as the major products. See Table 19. In contrast, strong electron-withdrawing substituents seem to disfavor the reduction of the phenyl ring. The hydrogenation of 2-methyl-6-fluoro-quinoline afforded 2-methyl-6-fluoro-1,2,3,4,-tetrahydro-quinoline exclusively in 72% yield. See second to last entry, Table 19. Zr-MTBC-CoH was also an active catalyst for hydrogenation of benzofuran. At a 0.2 mol % Co loading, benzofuran was completely hydrogenated to 2,3-dihydrobenzofuran in qualitative yield. See next to last entry, Table 19.
1: 78 %Spectr. 2: 22 %Spectr.	With sodium tetrahydroborate; hydrogen; cobalt(II) chloride In water at 130℃; for 17h; Green chemistry; chemoselective reaction;

Reference： [1]Fang, Minfeng; Sanchez-Delgado, Roberto A. [Journal of Catalysis, 2014, vol. 311, p. 357 - 368]
[2]Hoenel, Michael; Vierhapper, Friedrich W. [Journal of the Chemical Society. Perkin transactions I, 1980, p. 1933 - 1939]
[3]Kim, Sangmin; Loose, Florian; Bezdek, Máté J.; Wang, Xiaoping; Chirik, Paul J. [Journal of the American Chemical Society, 2019, vol. 141, # 44, p. 17900 - 17908]
[4]Fish, Richard H.; Thormodsen, Arne D.; Cremer Gregg A. [Journal of the American Chemical Society, 1982, vol. 104, # 19, p. 5234 - 5237]
[5]Ge, Danhua; Hu, Lei; Wang, Jiaqing; Li, Xingming; Qi, Fenqiang; Lu, Jianmei; Cao, Xueqin; Gu, Hongwei [ChemCatChem, 2013, vol. 5, # 8, p. 2183 - 2186]
[6]Jiang, He-Yan; Zheng, Xu-Xu [Catalysis Science and Technology, 2015, vol. 5, # 7, p. 3728 - 3734]
[7]Jiang, He-Yan; Zheng, Xu-Xu [Applied Catalysis A: General, 2015, vol. 499, p. 118 - 123]
[8]Ji, Pengfei; Manna, Kuntal; Lin, Zekai; Urban, Ania; Greene, Francis X.; Lan, Guangxu; Lin, Wenbin [Journal of the American Chemical Society, 2016, vol. 138, # 37, p. 12234 - 12242]
[9]Konnerth, Hannelore; Prechtl, Martin H. G. [Green Chemistry, 2017, vol. 19, # 12, p. 2762 - 2767]
[10]Wang, Xin; Chen, Wenxing; Zhang, Lei; Yao, Tao; Liu, Wei; Lin, Yue; Ju, Huanxin; Dong, Juncai; Zheng, Lirong; Yan, Wensheng; Zheng, Xusheng; Li, Zhijun; Wang, Xiaoqian; Yang, Jian; He, Dongsheng; Wang, Yu; Deng, Zhaoxiang; Wu, Yuen; Li, Yadong [Journal of the American Chemical Society, 2017, vol. 139, # 28, p. 9419 - 9422]
[11]Zhang, Fengwei; Ma, Chunlan; Chen, Shuai; Zhang, Jianfei; Li, Zhihong; Zhang, Xian-Ming [Molecular catalysis, 2018, vol. 452, p. 145 - 153]
[12]Current Patent Assignee: UNIVERSITY OF CHICAGO - US2018/361370, 2018, A1 Location in patent: Paragraph 0349
[13]Beller, Matthias; Dorcet, Vincent; Fischmeister, Cedric; Hervochon, Julien; Junge, Kathrin [Catalysis science and technology, 2020, vol. 10, # 14, p. 4820 - 4826]

5
[ 91-22-5 ]
[ 10500-57-9 ]
[ 635-46-1 ]
decahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen at 210℃; or Ru/C, 100 atm, 150 deg C, and competitive hydrogenation with isoquinoline;
	With hydrogen at 210℃; for 1h; or Ru/C, 100 atm, 150 deg C, and competitive hydrogenation with isoquinoline; other reaction times;
	With hydrogen In tetrahydrofuran at 150℃; for 1h;

	With hydrogen In cyclohexane at 100℃; for 3h; Autoclave;	Catalysis General procedure: The selective hydrogenation of quinoline was carried out in amagnetically stirred stainless-steel autoclave (100 ml). The air inthe autoclave was displaced by purging three times with hydrogenprior to use. The quantitative chemical analysis of hydrogenation products was done by GC-MS analysis. The GC separation was car-ried out on a ZB-5MS column (30 m × 0.25 mm, 0.25 m) using atemperature program of 35-200C at 5C/min. The instrumentused was a ThermoFinniganTrace GC-Polaris Q. The data was col-lected by using extracted ion chromatograms of marker m/z valuesfor each molecule from the total ion chromatograms (TIC).A freshly prepared suspension of nanoRuhectorite and thedesired amount of quinoline was used. Then the autoclave waspressurized with hydrogen (20-60 bar) and then heated to 100C.After the reaction, the pressure was released, the solution wasfiltered (0.22 m, PTFE) and analyzed in order to determine thesubstrate conversion and selectivity (in %). The catalytic reactionwas followed by gas chromatography coupled to a mass detector.The products were separated on an apolar column and identifiedby their retention time and their mass spectrum using the electronimpact (EI) ionization method.
	With hydrogen In tetrahydrofuran at 60℃; Autoclave; Glovebox;	3.3 General procedure for the catalytic hydrogenation reactions General procedure: Autoclave Par 477 equipped with PID control temperature and reservoir for kinetic measurements and HEL 24 Cat reactor for substrate scope were used as reactors for the hydrogenation reactions. In a typical experiment, the autoclave was charged in the glove-box with the desired Rh NPs (1.25 or 0.625mol%; the catalyst concentration was calculated based on the total number of metallic Rh atoms in the surface of the NPs) and the substrate (0.124M) in THF. Molecular hydrogen was then introduced until the desired pressure was reached and the reaction was stirred for the desired reaction time at the selected temperature. At the end of the reaction, the autoclave was depressurised and the solution was filtered through silica for subsequent analysis by GC. The conversion and selectivities for each reaction product were determined by GC-FID on an Agilent Technologies 7890A spectrometer, with a HP-5 column (30m×0.25mm×0.25μm) using undecane as internal standard. TOF was defined as moles of products per mol Rh at the surface of the NPs per hour.
10.7 %Chromat.	With hydrogen In water at 50℃; for 10h; Autoclave;
	With hydrogen In isopropyl alcohol at 80℃; for 4h; Molecular sieve; Autoclave; chemoselective reaction;	2.7. Catalytic test in quinoline and its derivatives selective hydrogenation General procedure: The hydrogenation of quinoline was performed in a 60 mL highpressure reactor equipped with a pressure gauge, a magnetic stirrer,and an electric temperature controller. For the selective hydrogenationof quinoline, 40 mg 5 wt%Ru/LDH and 1 mmol quinoline were dissolvedin 5 mL solvent. Before the reaction, the high pressure reactorwas purged four times with hydrogen to remove residual atmosphere,then pressurized to 3.0 MPa and set to stir. Upon heating the reactor upto the designated temperature, the reaction time was noted. After thereactor was cooled to 25 °C, the reaction mixture was separated bycentrifugation. The resulting solution was analyzed on Agilent 7820Agas chromatograph equipped with a flame ionization detector. Theidentification of the obtained products was carried on an Agilent7890B-5975 MSD-GC Mass spectrometer equipped with HP-5 columnalong with compared with known compounds.
	With tetrahydroxydiboron In water at 80℃; for 1h; Inert atmosphere;

Reference： [1]Okazaki, Hiroshi; Onishi, Kiyotaka; Soeda, Mahito; Ikefuji, Yoshio; Tamura, Ryuji; Mochida, Isao [Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 11, p. 3167 - 3174]
[2]Okazaki, Hiroshi; Onishi, Kiyotaka; Soeda, Mahito; Ikefuji, Yoshio; Tamura, Ryuji; Mochida, Isao [Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 11, p. 3167 - 3174]
[3]Location in patent: experimental part Fang, Minfeng; MacHalaba, Nataliya; Sanchez-Delgado, Roberto A. [Dalton Transactions, 2011, vol. 40, # 40, p. 10621 - 10632]
[4]Sun, Bing; Khan, Farooq-Ahmad; Vallat, Armelle; Süss-Fink, Georg [Applied Catalysis A: General, 2013, vol. 467, p. 310 - 314]
[5]Martinez-Espinar, Francisco; Blondeau, Pascal; Nolis, Pau; Chaudret, Bruno; Claver, Carmen; Castillón, Sergio; Godard, Cyril [Journal of Catalysis, 2017, vol. 354, p. 113 - 127]
[6]Ren, Yongshen; Wang, Yanxin; Li, Xun; Zhang, Zehui; Chi, Quan [New Journal of Chemistry, 2018, vol. 42, # 20, p. 16694 - 16702]
[7]Zhang, Sishi; Xu, Jie; Cheng, Hongmei; Zang, Cuicui; Sun, Bin; Jiang, Heyan; Bian, Fengxia [Applied Catalysis A: General, 2020, vol. 596]
[8]Kalanthoden, Abdul Nasar; Zahir, Md. Hasan; Aziz, Md. Abdul; Al-Najar, Basmah; Rani, S. Kutti; Shaikh, M. Nasiruzzaman [Chemistry - An Asian Journal, 2022, vol. 17, # 3]

6
[ 394-68-3 ]
[ 91-22-5 ]
[ 10500-57-9 ]
[ 635-46-1 ]
[ 75414-02-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 1933 - 1939

7
[ 10500-57-9 ]
[ 3085-76-5 ]
[ 53400-61-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With n-butyllithium In hexane; benzene	2 8-Cyano-5,6,7,8-tetrahydroquinoline EXAMPLE 2 8-Cyano-5,6,7,8-tetrahydroquinoline A solution of 5,6,7,8-tetrahydroquinoline (6.5 ml, 50 mM) in benzene (35 ml) maintained below 10° was treated with 1.6M butyl lithium in hexane (31.25 ml, 50 mM). The resulting anion solution was heated to reflux then treated with a solution of diisopropylcyanamide (6.3 g, 50 mM) in benzene (15 ml). After 15 min. the mixture was cooled and quenched with water (20 ml). The organic phase was separated, dried and evaporated. Distillation of the residue gave the title compound (5.6 g, 71%) Bp. 135°-140°/2 mm, identical with authentic material. Hydrochloride mp 185° C.--see Example 37 UK Pat. No. 1,432,378.
	In hexane; toluene at 5℃; for 0.5h; other dialkyl cyanamides, solvents, temperatures;
	With n-butyllithium; diisopropylamine 1) hexane, toluene, 5 deg C; 2) toluene, 0.5 h; Yield given. Multistep reaction;

Reference： [1]Current Patent Assignee: PFIZER INC - US4529798, 1985, A
[2]Crossley, Roger; Shepherd, Robin G. [Journal of the Chemical Society. Perkin transactions I, 1985, p. 2479 - 2482]
[3]Crossley, Roger; Shepherd, Robin G. [Journal of the Chemical Society. Perkin transactions I, 1985, p. 2479 - 2482]

8
[ 10500-57-9 ]
[ 6276-54-6 ]
[ 112668-88-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; sodium amide 2) 2 h; Yield given. Multistep reaction;
	With sodium amide In ammonia	1.a 2-[3-(5,6,7,8-Tetrahydroquinol-8-yl)propylamino]-5-[1-oxopyrid-4-ylmethyl]-4(1H)-pyrimidone (a) 5,6,7,8-Tetrahydroquinoline (20 g) was added quickly to sodamide (17.6 g) in liquid ammonia (250 ml) to give a dark red coloured solution. 3-Chloropropylamine hydrochloride (28.9 g) was added in portions over four hours when loss of colour was permanent after which the reaction was stirred for a further 2 hours and then quenched with ammonium chloride (20 g). The liquid ammonia was allowed to evaporate and the residues were partitioned between chloroform and water. The pH was lowered to 6 and the chloroform layer was discarded. The aqueous layer was basified (pH 12-14), and extracted with chloroform, the chloroform extracts were dried, combined, evaporated and the residue was vacuum distilled to give 3-(5,6,7,8-tetrahydroquinol-8-yl)propylamine (7.58 g), b.p. 92°-94° C. at 0.1 mm Hg.
	With sodium amide In ammonia	2.a EXAMPLE 2 (a) 5,6,7,8-Tetrahydroquinoline (20 g) was added quickly to sodamide (17.6 g) in liquid ammonia (250 ml) to give a dark red coloured solution. 3-Chloropropylamine hydrochloride (28.9 g) was added in portions over four hours when loss of colour was permanent after which the reaction was stirred for a further 2 hours and then quenched with ammonium chloride (20 g). The liquid ammonia was allowed to evaporate and the residues were partitioned between chloroform and water. The pH was lowered to 6 and the chloroform layer was discarded. The aqueous layer was basified (pH 12-14), and extracted with chloroform, the chloroform extracts were dried, combined, evaporated and the residue was vacuum distilled to give 3-(5,6,7,8-tetrahydroquinol-8-yl) propylamine (7.58 g), b.p. 92°-94° C. at 0.1 mm Hg.

Reference： [1]Cooper; Durant; Ganellin; Ife; Meeson; Sach [Il Farmaco, 1991, vol. 46, # 1, p. 3 - 19]
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4727076, 1988, A
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4764519, 1988, A

9
[ 10500-57-9 ]
[ 100-52-7 ]
[ 28707-60-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With acetic anhydride at 170℃; for 17h; Heating;
87%	With sodium acetate; acetic acid at 120℃; for 3h;
72%	With acetic anhydride at 170℃;

Reference： [1]Thummel, Randolph P.; Lefoulon, Francois; Cantu, David; Mahadevan, Ramanathan [Journal of Organic Chemistry, 1984, vol. 49, # 12, p. 2208 - 2212]
[2]Motiur Rahman; Jeong, Byeong-Seon; Kim, Dong Hyeon; Park, Jung Ki; Lee, Eung Seok; Jahng, Yurngdong [Tetrahedron, 2007, vol. 63, # 11, p. 2426 - 2431]
[3]Takizawa, Shin-Ya; Sasaki, Yuka; Akhtaruzzaman; Echizen, Hidenori; Nishida, Jun-Ichi; Iwata, Takeshi; Tokito, Shizuo; Yamashita, Yoshiro [Journal of Materials Chemistry, 2007, vol. 17, # 9, p. 841 - 849]

10
[ 10500-57-9 ]
[ 100-52-7 ]
[ 28707-60-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With acetic anhydride at 170℃; for 17h;
91%	With acetic anhydride at 155℃;
66%	With acetic anhydride at 170℃;

	With acetic anhydride at 180℃;
	Stage #1: 5,6,7,8-tetrahydroquinoline; benzaldehyde With acetic anhydride at 165℃; for 16h; Stage #2: With sodium hydroxide In water at 20℃;	A solution of 5,6,7,8-tetrahydroquinoline (18.2 g, 137 mmol), benzaldehyde (17.67 g, 166.0 mmol), and acetic anhydride (24.5 mL, 254 mmol) was heated under a nitrogen environment at 165° C. for 16 hours. The reaction mixture was cooled to room temperature. Crushed ice was added, and the mixture was slowly basified with NaOH (solid then 2 N NaOH) to pH around 7. The aqueous layer was extracted with hexane/ethyl acetate (1:1 solution) 3 times. The pooled organic layers were dried over magnesium sulfate. The mixture was filtered, and the solvents were removed under vacuum to give 8-benzylidene-5,6,7,8-tetrahydro-quinoline (Intermediate 1) as a brown solid. A solution of Intermediate 1 in dichoromethane (100 mL) and methanol (500 mL) was cooled to -78° C. (dry ice/acetone bath), and charged with ozone/oxygen (3 psi, 1.5 ampere). The dark brown solution turned yellow after several hours. When Intermediate 1 was consumed (TLC), ozone/oxygen flow was stopped. The reaction mixture was purged with nitrogen for 10 minutes. Methyl sulfide (6 mL) was added, and the mixture was stirred for 30 minutes at room temperature. The solvents were removed under vacuum. The residue was dissolved in 1 N HCl (500 mL), and washed with diethyl ether (4×150 mL). The aqueous layer was basified to pH 7 with NaOH (s), and extracted with ethyl acetate (2×200 mL). The pooled ethyl acetate layers were dried over magnesium sulfate. The mixture was filtered and the solvent was removed under vacuum. The residue was purified by chromatography on silica gel with 90% EtOAc: hexane to give a clean product. The aqueous layer was extracted with chloroform/isopropanol (3:1) several times. The pooled chloroform/isopropanol layers were dried over magnesium sulfate. The mixture was filtered and the solvents were removed under vacuum to give 6,7-dihydro-5H-quinolin-8-one (Intermediate 2), 17.89 g (122.0 mmol, 89% over 2 steps).
	Stage #1: 5,6,7,8-tetrahydroquinoline; benzaldehyde With acetic anhydride at 165℃; for 16h; Stage #2: With sodium hydroxide In water at 0 - 20℃;	Preparation of (+)-7-(5-Methyl-1 H-imidazol-4-ylmethyl)-5,6,7,8-tetrahydro-quinoline (8)KOH,trap 1 8-Benzylidene-5,6,7,8-tetrahydro-quinoline (2): A solution of 5,6,7,8-2 tetrahydroquinoline (182 g, 137 mmol), benzaldehyde (177 g, 166 mmol), and acetic3 anhydride (245 mL, 254 mmol) was heated at 1650C for 16 h The reaction mixture was4 cooled to room temperature (rt) Crushed ice was added, and the mixture was slowly5 basified with NaOH (solid and 2 M NaOH) to pH - 7 The aqueous layer was extracted with6 hexane/ethyl acetate (1 1 solution) 3 times The pooled organic layers were dried over7 magnesium sulfate The mixture was filtered, and the solvents were removed under vacuum8 to give 8-benzylιdene-5,6,7,8-tetrahydro-quιnolιne (2) as a brown solid
	In acetic anhydride at 170℃; for 12h;	1.1 In a nitrogen atmosphere, 150 mL of benzaldehyde was added to acetic anhydride (180 mL) solution of 65 mL of 5,6,7,8-tetrahydroquinoline, and stirred at 170°C for 12 hours. The reaction liquid was cooled to room temperature, and the excess reagent was evaporated off under reduced pressure. Then, aqueous saturated sodium hydroxide solution was added thereto, and extracted with ethyl acetate; and the ethyl acetate layer was washed with saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, and the residue was crystallized from ethyl acetate/hexane to obtain 96.4 g of the entitled compound as a pale brown solid.

Reference： [1]Westerwelle, Ulrich; Esser, Achim; Risch, Nikolaus [Chemische Berichte, 1991, vol. 124, # 3, p. 571 - 576]
[2]Location in patent: scheme or table Boggs, Sharon; Elitzin, Vassil I.; Gudmundsson, Kristjan; Martin, Michael T.; Sharp, Matthew J. [Organic Process Research and Development, 2009, vol. 13, # 4, p. 781 - 785]
[3]Tobin, John B.; Frey, Perry A. [Journal of the American Chemical Society, 1996, vol. 118, # 49, p. 12253 - 12260]
[4]Huang; Cabell; Anslyn [Tetrahedron Letters, 1990, vol. 31, # 51, p. 7411 - 7414]
[5]Current Patent Assignee: ABBVIE INC - US2007/179182, 2007, A1 Location in patent: Page/Page column 7-8
[6]Current Patent Assignee: ABBVIE INC - WO2008/88936, 2008, A1 Location in patent: Page/Page column 14; 15
[7]Current Patent Assignee: MERCK & CO INC - EP1726590, 2006, A1 Location in patent: Page/Page column 32-33

11
[ 10500-57-9 ]
[ 70-11-1 ]
[ 102408-79-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	In acetonitrile	2.a 1-Benzoyl-3-cyano-6,7,8,9-tetrahydro-pyrrolo[1,2-a]quinoline a) 1-(Phenacyl)-5,6,7,8-tetrahydro-quinolinium bromide The title compound was prepared from 2-bromo-1-phenyl-ethanone (507.7 mg, 2.55 mmol), 5,6,7,8-tetrahydro-quinoline (275 μL, 2.13 mmol) and acetonitrile (4.2 mL), similar to Example 1a, and yielded 694 mg (98%) as a light tan solid. 1H NMR (DMSO-d6): 8.80 (d, J=6.05 Hz, 1H), 8.45 (d, J=7.70 Hz, 1H), 8.11 (d, J=7.97 Hz, 2H), 8.00 (dd, J=7.69, 6.31 Hz, 1H), 7.82 (t, J=7.42 Hz, 1H), 7.68 (t, J=7.56 Hz, 1H), 6.52 (s, 2H), 3.02 (t, J=6.18 Hz, 2H), 2.92 (t, J=6.18 Hz, 2H), 1.85 (m, 2H), 1.77 (m, 2H).
95%	In acetone 1) 2 h, reflux; 2) room temp., overnight;

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2005/14759, 2005, A1 Location in patent: Page/Page column 15
[2]Noguchi; Tanigawa; Kajigaeshi [Journal of Heterocyclic Chemistry, 1985, vol. 22, # 4, p. 1049 - 1053]

12
[ 10500-57-9 ]
decahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen at 210℃; or Ru/C, 100 atm, 150 deg C, and competitive hydrogenation with 5,6,7,8-tetrahydroisoquinoline;
	With hydrogen at 300℃; for 2.5h;	3.4. Catalytic performances and kinetics of quinoline HDN General procedure: A whole reaction network of quinoline HDN is shown in Scheme 2[3-5,25,26]. Firstly, the heterocyclic ring of quinoline (Q) is hydrogenatedrapidly to form 1,2,3,4-tetrahydroquinoline (THQ-1) and anequilibrium between them is established [27-29]. Thus, Q and THQ-1are lumped together as the original reactant to calculate the conversion(Conv., including all conversion mentioned without further description): where CfQ, CpQ and CpTHQ-1 are the concentrations of quinoline (Q) in feed,Q in product and 1,2,3,4-tetrahydroquinoline (THQ-1) in product, respectively.Also, the carbocyclic ring of Q can be hydrogenated to form5,6,7,8-tetrahydroquinoline (THQ-5). Both THQ-1 and THQ-5 can befurther hydrogenated to form decahydroquinoline (DHQ). Then, the firsthydrogenolysis step involving CeN bond cleavage takes place on THQ-1and DHQ to form propylaniline (OPA) and propylcyclohexylamine(PCHA), respectively. Afterwards, the nitrogen atom of PCHA is removedvia a Hofmann elimination to form propylcyclohexene (PCHE), andpropylbenzene (PB) could be formed via a direct denitrogenation (DDN) of OPA. Finally, propylcyclohexane (PCH) is formed via hydrogenation ofPCHE. Besides, PCHE could be formed via hydrogenation of PB. Theselectivities (Sel.) are calculated by the equation as follows

Reference： [1]Okazaki, Hiroshi; Onishi, Kiyotaka; Soeda, Mahito; Ikefuji, Yoshio; Tamura, Ryuji; Mochida, Isao [Bulletin of the Chemical Society of Japan, 1990, vol. 63, # 11, p. 3167 - 3174]
[2]Jiang, Zongxuan; Li, Can; Liu, Tiefeng; Liu, Xinyi; Zhang, Cen [Applied Catalysis A: General, 2020, vol. 604]

13
[ 10500-57-9 ]
[ 10343-99-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With rhodium on alumina; hydrogen In acetic acid at 55℃; for 72h;

Reference： [1]Meyers; Milot, Guy [Journal of the American Chemical Society, 1993, vol. 115, # 15, p. 6652 - 6660]

14
[ 938-33-0 ]
[ 10500-57-9 ]
[ 53899-17-5 ]
[ 75414-07-2 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 1933 - 1939

15
[ 2568-20-9 ]
[ 10500-57-9 ]

Yield	Reaction Conditions	Operation in experiment
77%	With hydroxylamine hydrochloride In ethanol at 80℃; for 3h;
74%	With hydroxylamine hydrochloride In ethanol for 2h; Heating;
43%	With hydroxylamine hydrochloride In ethanol for 2h; Heating;

40%

With hydroxylamine hydrochloride In ethanol for 2h; Heating;

Reference： [1]Pham, Van Cuong; Jossang, Akino; Chiaroni, Angèle; Sévenet, Thierry; Bodo, Bernard [Tetrahedron Letters, 2002, vol. 43, # 42, p. 7565 - 7568]
[2]Epsztajn, Jan; Bieniek, Adam; Brzezinski, Jacek Z. [Polish Journal of Chemistry, 1980, vol. 54, # 2, p. 341 - 347]
[3]Crabb, Trevor A.; Turner, Christopher H. [Journal of the Chemical Society. Perkin transactions II, 1980, p. 1778 - 1782]
[4]Crabb, Trevor A.; Jupp, Philip A. [Journal of the Chemical Society. Perkin transactions I, 1985, p. 913 - 918]

16
[ 10500-57-9 ]
[ 14631-48-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dihydrogen peroxide In acetic acid at 70 - 80℃; for 1h;
99%	With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; water at 24℃; for 12h;
98%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃;	1 3-Chloroperoxybenzoic acid (m-CPBA, 10.5 g, 45 mmol) was added to a solution of 5,6,7, 8-tetrahydroquinoline (5.0 g, 37.5 mmol) in CH2C^ (350 mL) at room temperature. After the reaction mixture was stirred overnight, it was quenched by a IM aqueous sodium hydroxide solution and then a saturated aqueous NaCl solution. CH2Cl2 extracted the mixture. The combined organic layers were dried and concentrated. The residue thus obtained was purified by silica gel column chromatography to afford compound 1-1 (5.5 g, 98%). ESI-MS (M+H+) = 150.

97%	With 3-chloro-benzenecarboperoxoic acid In ethyl acetate at 20℃; for 2h;	37 Reference Example 37 Reference Example 37 5,6,7,8-Tetrahydroquinoline N-oxide 5,6,7,8-Tetrahydroquinoline (3.0 g, 22.5 mmol) was dissolved in ethyl acetate (15 ml), and 3-chloroperbenzoic acid (ca. 70 %, 5.6 g, 22.5 mmol) was added thereto.. The reaction mixture was stirred at room temperature for 2 days, subjected to a silica gel column chromatography and eluted with ethyl acetate-ethanol (5:1, v/v) to give the titled compound (3.4 g, 97 %).1H-NMR (CDCl3) δ: 1.73-1.95 (4H, m), 2.77 (2H, t, J = 6.0 Hz), 2.95 (2H, t, J = 6.0 Hz), 6.98-7.06 (2H, m), 8.14 (1H, d, J = 5.4 Hz).
96%	With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; water at 20℃; for 15h;
89%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; Inert atmosphere;
81%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 19h;
81%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃;	5,6,7,8-Tetrahydroquinoline 1-oxide (29) 5,6,7,8-Tetrahydroquinoline (300 mg, 2.252 mmol, 1.0 eq) and 3-chlorobenzoperoxoic acid(466 mg, 2.703 mmol, 1.2 eq) were dissolved in DCM (10 mL) and stirred at rt overnight. Thereaction was quenched with 1 M NaOH aq (15 mL) and the product extracted with DCM. Thecombined organic layers were dried over Na2SO4 and the solvent was evaporated. Purificationby column chromatography (eluent: DCM/MeOH = 19:1, Rf = 0.3) afforded 29 as a yellowishsolid (271 mg, 1.816 mmol, 81%)
	With 3-chloro-benzenecarboperoxoic acid In dichloromethane
	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 2h;
	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 16h;
	With 3-chloro-benzenecarboperoxoic acid In chloroform at 0 - 20℃; for 12h;

Reference： [1]Jacobs, Christoph; Frotscher, Martin; Dannhardt, Gerd; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2000, vol. 43, # 9, p. 1841 - 1851]
[2]Coperet, Christophe; Adolfsson, Hans; Khuong, Tinh-Alfredo V.; Yudin, Andrei K.; Sharpless, K. Barry [Journal of Organic Chemistry, 1998, vol. 63, # 5, p. 1740 - 1741]
[3]Current Patent Assignee: TAIGEN BIOPHARMACEUTICALS HOLDINGS LTD. - WO2008/95058, 2008, A1 Location in patent: Page/Page column 18
[4]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1424336, 2004, A1 Location in patent: Page 107
[5]Kaiser, Stefan; Smidt, Sebastian P.; Pfaltz, Andreas [Angewandte Chemie - International Edition, 2006, vol. 45, # 31, p. 5194 - 5197]
[6]Zhu, Ze-Lin; Wang, Sheng-Fu; Fu, Li-Wen; Tan, Ji-Hua; Cao, Chen; Yuan, Yi; Yiu, Shek-Man; Zhang, Ye-Xin; Chi, Yun; Lee, Chun-Sing [Chemistry - A European Journal, 2022, vol. 28, # 4]
[7]Martin, Benedikt; Schepmann, Dirk; Bernal, Freddy A.; Schmidt, Thomas J.; Che, Tao; Loser, Karin; Wünsch, Bernhard [ChemMedChem, 2020, vol. 15, # 15, p. 1408 - 1420]
[8]Antoni, Frauke; Wifling, David; Bernhardt, Günther [European Journal of Medicinal Chemistry, 2021, vol. 210]
[9]Guay, Daniel; Gauthier; Dufresne; Jones; McAuliffe; McFarlane; Metters; Prasit; Rochette; Roy; Sawyer; Zamboni [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 5, p. 453 - 458]
[10]Higashibayashi, Syuhei; Mori, Tomonori; Shinko, Kazuyuki; Hashimoto, Kimiko; Nakata, Masaya [Heterocycles, 2002, vol. 57, # 1, p. 111 - 122]
[11]Mazet, Clement; Roseblade, Stephen; Koehler, Valentin; Pfaltz, Andreas [Organic Letters, 2006, vol. 8, # 9, p. 1879 - 1882]
[12]Zhang, Wen-Man; Dai, Jian-Jun; Xu, Jun; Xu, Hua-Jian [Journal of Organic Chemistry, 2017, vol. 82, # 4, p. 2059 - 2066]

17
C₁₇H₁₆F₅NO₃ [ No CAS ]
[ 10500-57-9 ]
3-methoxy-2-methyl-4,5,6,7-tetrahydro-1<i>H</i>-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 62% 2: 21%	Stage #1: C₁₇H₁₆F₅NO₃ With tetrabutyl-ammonium chloride; triethylamine In N,N-dimethyl-formamide at 80℃; for 4h; Stage #2: With pyrrolidine at 80℃; for 4h;

Reference： [1]Tsutsui, Hironori; Narasaka, Koichi [Chemistry Letters, 2001, # 6, p. 526 - 527]

18
[ 148-24-3 ]
[ 10500-57-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With aluminium trichloride; cyclohexane at 90℃; for 15h;
	Multi-step reaction with 2 steps 1: cyclohexane; CF₃SO₃H; SbF₅ / 1.5 h / 20 °C 2: H₂O

Reference： [1]Koltunov, Konstantin Yu.; Prakash, G. K. Surya; Rasul, Golam; Olah, George A. [Journal of Organic Chemistry, 2002, vol. 67, # 12, p. 4330 - 4336]
[2]Koltunov; Repinskaya [Russian Journal of Organic Chemistry, 2000, vol. 36, # 3, p. 446 - 447]

19
[ 578-67-6 ]
[ 10500-57-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	With aluminium trichloride; cyclohexane at 90℃; for 90h;

Reference： [1]Koltunov, Konstantin Yu.; Prakash, G. K. Surya; Rasul, Golam; Olah, George A. [Journal of Organic Chemistry, 2002, vol. 67, # 12, p. 4330 - 4336]

20
[ 10500-57-9 ]
[ 58509-59-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium; lithium diisopropyl amide In hexane at -15℃; Stage #2: With isopentyl nitrite In hexane at -15℃; for 1h;
75%	With n-hexyllithium; diisopropylamine; isopentyl nitrite In tert-butyl methyl ether at -15℃; Large scale; regioselective reaction;
	Multi-step reaction with 3 steps 1.1: acetic anhydride / 12 h / 170 °C 2.1: ozone / methanol / 10 h / -78 °C 2.2: -78 - 20 °C 3.1: hydroxylamine hydrochloride / ethanol; water / 1 h / 110 °C

Reference： [1]McEachern; Yang; Chen; Skerlj; Bridger [Synthetic Communications, 2003, vol. 33, # 20, p. 3497 - 3502]
[2]Crawford, Jason B.; Chen, Gang; Gauthier, David; Wilson, Trevor; Carpenter, Bryon; Baird, Ian R.; McEachern, Ernie; Kaller, Alan; Harwig, Curtis; Atsma, Bem; Skerlj, Renato T.; Bridger, Gary J. [Organic Process Research and Development, 2008, vol. 12, # 5, p. 823 - 830]
[3]Current Patent Assignee: MERCK & CO INC - EP1726590, 2006, A1

21
[ 10500-57-9 ]
[ 56826-69-8 ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 2197 - 2205
[2]Chemical Communications,2019,vol. 55,p. 937 - 940
[3]Synthetic Communications,2003,vol. 33,p. 3497 - 3502
[4]Journal of the American Chemical Society,1996,vol. 118,p. 12253 - 12260
[5]Journal of Organic Chemistry,1984,vol. 49,p. 2208 - 2212
[6]Chemische Berichte,1991,vol. 124,p. 571 - 576
[7]Tetrahedron Letters,1990,vol. 31,p. 7411 - 7414
[8]Patent: EP1726590,2006,A1

22
[ 10500-57-9 ]
cis-cis-1,12-dibromo-dodeca-5,7-diene [ No CAS ]
cis-cis-N,N'-(dodeca-5,7-diene-1,12-diyl)-bis-(5,6,7,8-tetrahydroquinolinium)dibromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In acetonitrile for 24h; Heating / reflux;	5 cw-ci5-l,12-Dibromo-dodeca-5,7-diene was added to a solution of 5,6,7,8-tetrahydro- quinoline (3 mmol) in acetonitrile and the solution refluxed for 24 hours. The acetonitrile was20 removed in vacuum and the resulting residue was partitioned between ether and water. The aqueous layer was washed extensively with ether until no quinoline left in the aqueous layer. The resulting aqueous solution of the product was lyophilized to yield the pure product. (75%).1HNMR (300MHz, D2O, ppm), 8.35 (d, J=6.3, 2H), 7.97 (d, J=8.1, 2H), 7.52 (dd, J=8.1, J=6.3, 2H), 6.16-6.22 (m, 2H), 5.32-5.42 (m, 2H), 4.30 (t, J=7.8, 4H), 2.92 (t, J=6.2, 4H), 2.7925 (t, J=6.2, 4H), 2.09 (q, J=7.2, 4H), 1.60-1.83 (m, 12H), 1.36 (p, J=7.5, 4H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF KENTUCKY - WO2007/149163, 2007, A2 Location in patent: Page/Page column 27

23
[ 10500-57-9 ]
[ 2778-48-5 ]
N,N'-[1,4-phenylenedi-(4-butanyl)]-bis-(5,6,7,8-tetrahydroquinolinium)dibromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In acetonitrile for 24h; Heating / reflux;	15 l,4-i?zs-(4-bromo-butyl)-benzene was added to a solution of tetrahydroquinoline (3 mmol) in acetonitrile and the solution refluxed for 24 hours. The acetonitrile was removed in vacuum and the resulting residue was partitioned between ether and waterí The aqueous layer25 was washed extensively with ether until no tetrahydroquinoline left in the aqueous layer. The resulting aqueous solution of the product was lyophilized to yield the pure product. (75%).ηNMR (300MHZ, D2O, ppm), 8.30 (d, J=6.3, 2H), 7.95 (d, J=7.8, 2H), 7.49 (dd, J=8.1 , J=6.3, 2H), 7.02 (s, 4H), 4.28 (t, 7.5, 4H), 2.83 (t, J=7.5, 4H), 2.77 (t, J=7.5, 4H), 2.49 (t, J=7.5, 4H), 1.66-1.80 (m, 8H), 1.35-1.63 (m, 8H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF KENTUCKY - WO2007/149163, 2007, A2 Location in patent: Page/Page column 32

24
[ 10500-57-9 ]
4,4'-bis-(3-bromo-propyl)-biphenyl [ No CAS ]
N,N'-[(1,1'-biphenyl)-4,4'-di-(3-propanyl)]-bis-[5,6,7,8-tetrahydroquinolinium]dibromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In acetonitrile for 24h; Heating / reflux;	75 4,4'-i?«-(3-bromo-propyl)-biphenyl was added to a solution of 5,6,7,8- tetrahydroquinoline (3 mmol) in acetonitrile and the solution refluxed for 24 hours. The acetonitrile was removed in vacuum and the resulting residue was partitioned between ether and10 water. The aqueous layer was washed extensively with ether until no 5,6,7,8- tetrahydroquinoline left in the aqueous layer. The resulting aqueous solution of the product was lyophilized to yield the pure product. (75%).1HNMR (300MHz, D2O, ppm), 8.79 (d, J=6.3, 2H), 8.19 (d, J=7.2, 2H), 7.77 (dd, J=6.3, J=7.8, 2H), 7.54 (d, J=7.8, 4H), 7.36 (d, J=7.8, 4H), 4.59 (t, J=7.8, 4H), 3.07 (t, J=6.3, 4H), 2.97 (t, J=6.0, 4H), 2.87 (t, J=7.5, 4H), 2.30 (p, J=7.5, 4H), 1.93-15 1.99 (m, 4H), 1.81-1.87 (m, 4H). CNMR, 154.12, 145.55, 143.40, 139.94, 139.38, 138.83, 128.99, 126.66, 124.51, 56.85, 31.93, 31.52, 28.77, 26.88, 21.54, 20.63.
	In acetonitrile	75 Synthesis of compound N,N'-[(1,1'-biphenyl)-4,4'-di-(3-propanyl)]-bis-[5,6,7,8-tetrahydroquinolinium]dibromide Example 75 Synthesis of compound N,N'-[(1,1'-biphenyl)-4,4'-di-(3-propanyl)]-bis-[5,6,7,8-tetrahydroquinolinium]dibromide 4,4'-Bis-(3-bromo-propyl)-biphenyl was added to a solution of 5,6,7,8-tetrahydroquinoline (3 mmol) in acetonitrile and the solution refluxed for 24 hours. The acetonitrile was removed in vacuum and the resulting residue was partitioned between ether and water. The aqueous layer was washed extensively with ether until no 5,6,7,8-tetrahydroquinoline left in the aqueous layer. The resulting aqueous solution of the product was lyophilized to yield the pure product. (75%). 1H NMR (300 MHz, D2O, ppm), 8.79 (d, J=6.3, 2H), 8.19 (d, J=7.2, 2H), 7.77 (dd, J=6.3, J=7.8, 2H), 7.54 (d, J=7.8, 4H), 7.36 (d, J=7.8, 4H), 4.59 (t, J=7.8, 4H), 3.07 (t, J=6.3, 4H), 2.97 (t, J=6.0, 4H), 2.87 (t, J=7.5, 4H), 2.30 (p, J=7.5, 4H), 1.93-1.99 (m, 4H), 1.81-1.87 (m, 4H). CNMR, 154.12, 145.55, 143.40, 139.94, 139.38, 138.83, 128.99, 126.66, 124.51, 56.85, 31.93, 31.52, 28.77, 26.88, 21.54, 20.63.

Reference： [1]Current Patent Assignee: UNIVERSITY OF KENTUCKY - WO2007/149163, 2007, A2 Location in patent: Page/Page column 66
[2]Current Patent Assignee: UNIVERSITY OF UTAH; UNIVERSITY OF KENTUCKY - US2011/166177, 2011, A1

25
[ 638-56-2 ]
[ 10500-57-9 ]
N,N'-{2,2'-[oxybis-(2,1-ethandiyloxy)]bis-ethyl}-bis-(5,6,7,8-tetrahydroquinolinium)dichloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In acetonitrile for 24h; Heating / reflux;	84 1 -Chloro-2- {2-[2-(2-chloro-ethoxy)-ethoxy]-ethoxy} -ethane was added to a solution of tetrahydroquinoline (3 mmol) in acetonitrile and the solution refluxed for 24 hours. The acetonitrile was removed in vacuum and the resulting residue was partitioned between ether and water. The aqueous layer was washed extensively with ether until no tetrahydroquinoline left in the aqueous layer. The resulting aqueous solution of the product was lyophilized to yield the30 pure product. (75%).1HNMR (300MHz, D2O, ppm), 8.39 (d, J=6.3, 2H), 8.04 (d, J=8.1, 2H),7.55 (dd, J=8.1, J=6.3, 2H), 4.57 (t, J=4.5, 4H), 3.83 (t, J=4.5, 4H), 4.43-3.49 (m, 4H), 3.36-3.38 71(m 4H), 2.98 (t, 6.3, 4H), 2.82 (t, J=6.3, 4H), 1.79-1.83 (m, 4H), 1.63-1.69 (m, 4H). CNMR, 154.58, 145.92, 143.59, 139.99, 123.92, 70.19, 69.74, 68.40, 56.28, 49.10, 28.72, 27.26, 21.40, 20.45.

Reference： [1]Current Patent Assignee: UNIVERSITY OF KENTUCKY - WO2007/149163, 2007, A2 Location in patent: Page/Page column 70-71

26
[ 10500-57-9 ]
[ 298181-83-6 ]

Reference： [1]Synthetic Communications,2003,vol. 33,p. 3497 - 3502
[2]Organic Process Research and Development,2008,vol. 12,p. 823 - 830

27
[ 10500-57-9 ]
[ 106057-23-2 ]

Yield	Reaction Conditions	Operation in experiment
86%	With trichloroisocyanuric acid In dichloromethane Reflux;	5 6.1.5 8-Chloro-5,6,7,8-tetrahydroquinoline (28) To a solution of 5,6,7,8-tetrahydroquinoline (10 g, 60 mmol) in dichloromethane (200 mL) was added TCCA (21 g, 90 mmol). The reaction mixture was stirred at reflux overnight. After cooling to room temperature, the mixture was filtered. The filtrate was washed with saturated NaHCO3 aqueous solution (100 mL), dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10/1 to 5/1) to give the desired product (8.6 g, 86%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 4.4 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.18 (dd, J = 7.2, 4.8 Hz, 1H), 5.43 (s, 1H), 2.92-2.83 (m, 1H), 2.80-2.76 (m, 1H), 2.42-2.39 (m, 1H), 2.26-2.18 (m, 2H), 1.90-1.87 (m, 1H).
86%	With trichloroisocyanuric acid In dichloromethane Reflux;	BC.a Step a. 8-chloro-5,6,7,8-tetrahydroquinoline: A mixture of 5,6,7,8- tetrahydroquinoline (10 g, 60 mmol) in DCM (200 mL) was added TCCA (21 g, 90 mmol) and stirred at reflux overnight. The reaction mixture was filtered and the filtrate was solution was added saturated NaHC03aqueous solution (50 mL). The organic layer was dried over Na2S04, filtered and evaporated. The residue was purified by silica gel column chromatography(petroleum ether/ethyl acetate = 10/1 to 5/1) to give the desired product (8.6 g, 86%) as a yellow oil H NMR (400 MHz, CDC13) δ 8.53 (d, / = 4.6 Hz, 1H), 7.49 (d, / = 7.8 Hz, 1H), 7.19 (dd, / = 7.6, 4.8 Hz, 1H), 5.43 (d, / = 3.4 Hz, 1H), 2.97-2.88 (m, 1H), 2.81-2.76 (m, 1H), 2.40-2.38 (m, 1H), 2.29-2.16 (m, 2H), 1.91- 1.89 (m, 1H).
	Multi-step reaction with 2 steps 1: 100 percent / H₂O₂ / acetic acid / 1 h / 70 - 80 °C 2: POCl₃; Et₃N / CH₂Cl₂ / 0.25 h

Reference： [1]Li, Zhanhui; Wang, Yujie; Fu, Chunyan; Wang, Xu; Wang, Jun Jun; Zhang, Yi; Zhou, Dongping; Zhao, Yuan; Luo, Lusong; Ma, Haikuo; Lu, Wenfeng; Zheng, Jiyue; Zhang, Xiaohu [European Journal of Medicinal Chemistry, 2018, vol. 149, p. 30 - 44]
[2]Current Patent Assignee: SUZHOU YUNXUAN YIYAO KEJI YOUXIAN GONGSI; CGENETECH SUZHOU CHINA - WO2019/60860, 2019, A1 Location in patent: Paragraph 00249-00251
[3]Jacobs, Christoph; Frotscher, Martin; Dannhardt, Gerd; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2000, vol. 43, # 9, p. 1841 - 1851]

28
[ 10500-57-9 ]
tert-Butyl-[(4aS,8aR)-1-(4a,5,6,7,8,8a-hexahydro-4H-quinolin-1-yl)-meth-(E)-ylidene]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: Na, EtOH 2: 79 percent / (NH₄)2SO₄ / xylene / 48 h / Heating 3: 1.) t-BuLi, 2.) CH₃I / 1.) ether, THF, pentane, -20 deg C, 2.5 h, 2.) ether, THF, pentane, HMPA, -55 deg C, overnight
	Multi-step reaction with 3 steps 1: Na, EtOH 2: 79 percent / (NH₄)2SO₄ / xylene / 48 h / Heating 3: 1.) 1.7 M t-BuLi in pentanes, 2.) pentynylcopper
	Multi-step reaction with 3 steps 1: Na, EtOH 2: 79 percent / (NH₄)2SO₄ / xylene / 48 h / Heating 3: 1.) t-BuLi / 1.) ether, THF, pentane, -20 deg C, 2.5 h, 2.) ether, THF, pentane, HMPA, -55 deg C, overnight

	Multi-step reaction with 3 steps 1: Na, EtOH 2: 76 percent / (NH₄)2SO₄ / xylene / 48 h / Heating 3: 1.) t-BuLi / 1.) ether, THF, pentane, -20 deg C, 2.5 h, 2.) ether, THF, pentane, -78 deg C, overnight
	Multi-step reaction with 3 steps 1: 70 percent / H₂, 5percent Rh on alumina / acetic acid / 72 h / 55 °C / 2068.6 Torr 2: 76 percent / (NH₄)2SO₄ / xylene / 48 h / Heating 3: 1.) t-BuLi / 1.) ether, THF, pentane, -20 deg C, 2.5 h, 2.) ether, THF, pentane, -78 deg C, overnight

Reference： [1]Meyers; Milot, Guy [Journal of the American Chemical Society, 1993, vol. 115, # 15, p. 6652 - 6660]
[2]Meyers; Milot, Guy [Journal of the American Chemical Society, 1993, vol. 115, # 15, p. 6652 - 6660]
[3]Meyers; Milot, Guy [Journal of the American Chemical Society, 1993, vol. 115, # 15, p. 6652 - 6660]
[4]Meyers; Milot, Guy [Journal of the American Chemical Society, 1993, vol. 115, # 15, p. 6652 - 6660]
[5]Meyers; Milot, Guy [Journal of the American Chemical Society, 1993, vol. 115, # 15, p. 6652 - 6660]

29
[ 938-33-0 ]
petroleum ether [ No CAS ]
[ 10500-57-9 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 1933 - 1939

30
[ 1128-00-3 ]
[ 10500-57-9 ]

Reference： [1]Helvetica Chimica Acta,1945,vol. 28,p. 1684,1690

31
[ 10500-57-9 ]
[ 14631-47-1 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5,6,7,8-tetrahydroquinoline With dihydrogen peroxide; acetic acid In water at 70℃; Stage #2: With sodium carbonate In chloroform for 1h; Stage #3: With acetic anhydride at 90℃;	AMD7474: Preparation of 8-hydroxy-5,6,7,8-tetrahydroquinoline. To a stirred solution of 5,6,7,8-tetrahydroquinoline (74.3 g, 0.558 mol) in glacial acetic acid (275 mL) at room temperature was added 30% H2O2 (55 mL) and the solution was heated to 70° C. After 6 hours, the reaction mixture was cooled to room temperature, additional H2O2 (55 mL) was added, and the solution was heated at 70° C. overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in CHCl3 (300 mL) and treated with solid Na2CO3 (175 g). After 1 hour, the supernatant was decanted and the residue was washed with warm CHCl3 (3×300 mL). The combined supernatants were filtered and concentrated to provide 121 g of a yellow oil. The oil was dissolved in acetic anhydride (400 mL) and heated at 90° C. overnight. The mixture was cooled to room temperature and concentrated. Distillation (Kugelrohr, bp 110-140° C. @ 1 Torr) of the resultant oil provided 99.2 g of 8-acetoxy-5,6,7,8-tetrahydroquinoline.
	With dihydrogen peroxide; acetic anhydride; potassium carbonate In chloroform; acetic acid	1.A Step A Step A 8-Acetoxy-5,6,7,8-tetrahydroquinoline To 9.7 g of 5,6,7,8-tetrahydro quinoline in 36 mL of acetic acid was added 7.2 mL of 30% hydrogen peroxide and the mixture was warmed to 70° C. for 5 h. Another 7.2 mL of hydrogen peroxide was added and the mixture was stirred an additional 12.5 h at 70° C. The solution was then concentrated in vacuo. Solid potassium carbonate (20 g) was then added followed by 20 mL of chloroform and the thick paste was stirred at 20° C. for 4 h. The paste was then extracted 4* with 50 mL portions of boiling chloroform by filtration. The combined filtrate was concentrated in vacuo to yield 18 g of yellow oil. Acetic anhydride (50 mL) was then added to this oil and the mixture was heated at 90° C. under argon for 5 h. The excess acetic anhydride was then distilled off in vacuo and the residual liquid was distilled via Kugelrohr at 0.5 torr and 150° C. to afford 12.3 g of product characterized by its NMR.
	Multi-step reaction with 2 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 19 h / 20 °C 2: 1 h / 120 °C

Reference： [1]Current Patent Assignee: SANOFI - US6750348, 2004, B1 Location in patent: Page column 15
[2]Current Patent Assignee: MERCK & CO INC - US5606054, 1997, A
[3]Martin, Benedikt; Schepmann, Dirk; Bernal, Freddy A.; Schmidt, Thomas J.; Che, Tao; Loser, Karin; Wünsch, Bernhard [ChemMedChem, 2020, vol. 15, # 15, p. 1408 - 1420]

32
[ 10500-57-9 ]
[ 536-38-9 ]
[ 155277-65-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In N,N-dimethyl-formamide; toluene	3 Preparation of 1-(4-chlorophenyl)-8,9-dihydro-7H-pyrrolo[3,2,1-ij]quinolin EXAMPLE 3 Preparation of 1-(4-chlorophenyl)-8,9-dihydro-7H-pyrrolo[3,2,1-ij]quinolin 5,6,7,8-Tetrahydroquinoline (35 g) was dissolved in 500 ml of toluene. To this solution was added 4-chlorophenacyl bromide (61.4 g) gradually and refluxed for 1 hour. The reaction mixture was cooled to room temperature, and depositing crystals were collected by filtration (86 g). These solids were dissolved in 500 ml of N,N-dimethylformamide. To this solution was added, molecular sieves 3A (50 g) and triethylamine (44 ml), then the reaction mixture was heated at 100° C. for 1 hour. The reaction mixture became dark brown. The dark brown solution that obtained after removing insoluble matter by filtration was concentrated under reduced pressure. The resultant brown solids were recrystallized from ethanol (300 ml), and the title compound was obtained as colorless leaflets (50 g). m.p.: 130.8°-131.1° C. IR: 2947, 2931, 2917, 2900, 2893, 1515, 1452, 1091, 837, 736 NMR (CDCl3): 7.7-7.2 m (6H), 6.4 dd (1H), 6.3 d (1H), 3.0 t (2H), 2.8 t (2H), 2.0 tt (2H)

Reference： [1]Current Patent Assignee: MOCHIDA PHARMACEUTICAL CO LTD - US5643920, 1997, A

33
[ 10500-57-9 ]
[ 108-24-7 ]
[ 100-52-7 ]
[ 28707-60-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5,6,7,8-tetrahydroquinoline; acetic anhydride; benzaldehyde at 170℃; for 20h; Stage #2: With sodium hydroxide In methanol; water at 20℃; for 2h;	1.A Step A: 8-Benzylidene-5.6.7.8-tetrahydroquinolineA mixture of 4.876 g (36.6 mmol) of 5,6,7,8-tetrahydroquinoline, 5.83g (54.9 mmol) benzaldehyde and 6.58 mL (69.6 mmol) of acetic anhydride was heated at 17O C for 20 hr. The resulting mixture was cooled to RT and volatiles distilled under vacuum. The residue was diluted with ~20 mL MeOH and 5 mL of %N aq. NaOH was added. The resulting mixture was stirred at RT for 2hr then diluted with ether. The layers were separated and the ether layer was wadhed with aq. NaOh, brine, dried over drying agent and filtered. The solvent was removed under vacuum and the residue was purified by column chromatography on silica gel eluting with hexanes/EtOAc (1/10 to 9/1) to afford the title compound as a light yellow solid. 1H-NMR (CDCIs): ? 8.52 (d of d, IH J = 1.6, 4.5 Hz), 8.02 (s, IH), 7.48 (d, 2H, J = 7.5Hz), 7.39- 7.44 (m, 3H), 7.29 (t, IH, J = 6.1 Hz), 7.11 (d of d, IH, J = 4.6, 2.9 Hz), 2.93-2.95 (m, 2H), 2.88 (t, 2H, J = 6.2 Hz), 1.86 - 1.91 (m, 2H), ppm. MS: 222 (MH)+

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/60346, 2006, A2 Location in patent: Page/Page column 21-22

34
[ 10500-57-9 ]
[ 22884-95-3 ]
5,6,7,8-Tetrahydro-8-(3,4-dimethylbenzoyl)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; In tetrahydrofuran; hexane;	EXAMPLE 14 5,6,7,8-Tetrahydro-8-(3,4-dimethylbenzoyl)quinoline 5,6,7,8-Tetrahydroquinoline (7.2g 0.054M) was dissolved in THF (50ml) and cooled to 0 C. 35ml of a solution of n-butyl lithium (1.6M in hexane) was added. The mixture was left for 20 minutes then a solution of 3,4,-dimethyl-benzonitrile (7g 0.053M) in THF (50ml) was added. The mixture was allowed to stand for 30 minutes them 2M HCl (100ml) was added. The mixture was allowed to stand for 16 hours after which the resulting yellow crystals were filtered off and washed with isopropyl alcohol then ether to give 6.17g of the title compound as the hydrochloride. The mother liquids were diluted with 2M HCl and extracted with hexane. A small quantity of solid was obtained filtered off and washed. with isopropyl alcohol then ether to give a further 2.2g of the title compound hydrochloride dihydrate m.p. 236-7 C. (Found: C, 67.3; H,7.4; N, 4.25; C18 H19 NO, HCl. 2H2 O requires C, 67.55; H, 7.2; N, 4.15%)

Reference： [1]Patent: US5001131,1991,A

35
[ 10500-57-9 ]
5,6,7,8-tetrahydro-8-lithioquinoline [ No CAS ]
[ 3085-76-5 ]
[ 53400-61-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With n-butyllithium In hexane	3 8-Cyano-5,6,7,8-tetrahydroquinoline EXAMPLE 3 8-Cyano-5,6,7,8-tetrahydroquinoline A solution of 8-lithio-5,6,7,8-tetrahydroquinoline (10 mM) was generated from 5,6,7,8-tetrahydroquinoline (1.3 ml), ether (6 ml) and 1.6M butyl lithium in hexane (6.25 ml), then added to a solution of diisopropylcyanamide (3.9 g, 30 mM) in ether (6 ml) at 0° C. Work up of the reaction mixture after 15 minutes as described in Example 2 gave the title compound in 85% yield.

Reference： [1]Current Patent Assignee: PFIZER INC - US4529798, 1985, A

Yield	Reaction Conditions	Operation in experiment
		The residual oil was distilled giving 5- oxo-5H-6,7,8-trihydroquinoline (21 g.) b.p. 133-4 C./15 mm. which was dissolved in diethylene glycol (190 ml.) and treated with hydrazine hydrate (14 g.) and sodium hydroxide (14 g.). The reaction mixture was heated at reflux for 30 minutes and then for 31/2 hours under a Dean and Stark water separator. The cooled reaction mixture was poured onto water (100 ml.), extracted with ether (3* 100 ml.) and the combined extracts dried and evaporated in vacuo. The residual oil was distilled giving the title compound as a colourless oil (10 g.) b.p. 100-5 C./15 mm.
		The residual oil was distilled giving 5-oxo-5H-6,7,8-trihydroquinoline (21 g.) b.p. 133-4 C/15 mm. which was dissolved in diethylene glycol (190 ml.) and treated with hydrazine hydrate (14 g.) and sodium hydroxide (14 g.). The reaction mixture was heated at reflux for 30 minutes and then for 31/2 hours under a Dean and Stark water separator. The cooled reaction mixture was poured onto water (100 ml.), extracted with ether (3 * 100 ml.) and the combined extracts dried and evaporated in vacuo. The residual oil was distilled giving the title compound as a colourless oil (10 g.) b.p. 100-5 C/15 mm.
		The residual oil was distilled giving 5-oxo-5H-6,7,8-trihydroquinoline (21 g.) b.p. 133-4 C/15 mm. which was dissolved in diethylene glycol (190 ml.) and treated with hydrazine hydrate (14 g.) and sodium hydroxide (14 g.). The reaction mixture was heated at reflux for 30 minutes and then for 31/2 hours under a Dean and Stark water separator. The cooled reaction mixture was poured onto water (100 ml.), extracted with ether (3 * 100 ml.) and the combined extracts dried and evaporated in vacuo. The residual oil was distilled giving the title compound as a colourless oil (10 g.) b.p. 100-5 C/15 mm.

The residual oil was distilled giving 5-oxo-5H-6,7,8-trihydroquinoline (21 g.) b.p. 133-4 C/15 mm. which was dissolved in diethylene glycol (190 ml.) and treated with hydrazine hydrate (14 g.) and sodium hydroxide (14 g.). The reaction mixture was heated at reflux for 30 minutes and then for 31/2 hours under a Dean and Stark water separator. The cooled reaction mixture was poured onto water (100 ml.), extracted with ether (3 * 100 ml.) and the combined extracts dried and evaporated in vacuo. The residual oil was distilled giving the title compound as a colourless oil (10 g.) b.p. 100-5 C/15 mm.

37
[ 10500-57-9 ]
[ 2290-65-5 ]
[ 108-18-9 ]
[ 53400-60-5 ]

Yield	Reaction Conditions	Operation in experiment
30%	With n-butyllithium In hexane; water; benzene	10 5,6,7,8-Tetrahydroquinoline-8-thiocarboxamide EXAMPLE 10 5,6,7,8-Tetrahydroquinoline-8-thiocarboxamide A solution of di-isopropylamine (33.3g, 0.33 mol) in benzene (150 ml) was cooled in ice and treated with 9% w/v butyl-lithium in hexane (237 ml, 0.33 mol). After 45 minutes the solution was treated with 5,6,7,8-tetrahydroquinoline (39.9 g, 0.3 mol) dropwise with stirring. After 1.5 hours trimethylsilyl-isothiocyanate (43.2 ml. 0.3 mol) was added and the resulting solution was allowed to stand at 0° C for 0.5 hours and at room temperature for 1 hour. Water (50 ml.) was added and the resulting mixture acidified with 2N HCl. The acid solution was separated, washed with ethyl acetate and the pH was adjusted to 9 with solid sodium carbonate. Extraction with chloroform followed by drying of the extract over MgSO4, filtration and evaporation gave a thick gum which crystallized on trituration with n-hexane. Recrystallisation from methanol gave 5,6,7,8-tetrahydroquinoline-8-thiocarboxamide (16g, 30%) m.p. 160°. The hydrochloride was prepared by dissolution of the free base in hot iso-propyl alcohol adding ethereal HCl solution and allowing to crystallise. m.p. 263-4°.

Reference： [1]Current Patent Assignee: PFIZER INC - US4000142, 1976, A

38
[ 10500-57-9 ]
[ 108-86-1 ]
[ 53400-58-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; lithium; phenyllithium In methanol; water	6.B B. B. Methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate A solution of 5,6,7,8-tetrahydroquinoline (14 g.) in dry ether (100 ml.) was added dropwise over 1/2 hour to an ethereal solution of phenyl lithium (prepared from bromobenzene (42 g.) and lithium (3.7 g.) in dry ether (300 ml.) and the reaction mixture stirred at room temperature for a further one hour. The cooled reaction mixture was saturated with dry CO2 gas, evaporated in vacuo and the residue treated with methanol previously saturated with dry HCl (500 ml.) and the solution heated at reflux for 12 hours. The solvent was removed in vacuo and the residue dissolved in water (50 ml.), extracted with ether (3 * 150 ml.) and the extracts discarded. The aqueous solution was made basic and extracted with ether (3 * 100 ml.). The combined ethereal extracts were dried, evaporated in vacuo and the residual oil distilled giving methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate as a colourless oil (13 g.) b.p. 92° C/0.05 mm. The hydrochloride was prepared by saturating an ethereal solution with dry HCl gas and recrystallising the resultant solid from methanol-ether to give the hydrochloride of the title compound as colourless needles mpt. 173° C. Found: C, 58.2; H, 6.3; N, 6.3%. C11 H13 NO2.HCl requires C, 58.0; H, 6.2; N, 6.2%.
	With hydrogenchloride; lithium; phenyllithium In methanol; water	6.B A. B. methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate. A solution of 5,6,7,8-tetrahydroquinoline (14 g.) in dry ether (100 ml.) was added dropwise over 1/2 hour to an ethereal solution of phenyl lithium (prepared from bromobenzene (42 g.) and lithium (3.7 g.) in dry ether (300 ml.) and the reaction mixture stirred at room temperature for a further one hour. The cooled reaction mixture was saturated with dry CO2 gas, evaporated in vacuo and the residue treated with methanol previously saturated with dry HCl (500 ml.) and the solution heated at reflux for 12 hours. The solvent was removed in vacuo and the residue dissolved in water (50 ml.), extracted with ether (3 * 150 ml.) and the extracts discarded. The aqueous solution was made basic and extracted with ether (3 * 100 ml.). The combined ethereal extracts were dried, evaporated in vacuo and the residual oil distilled giving methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate as a colourless oil (13 g.) b.p. 92° C/0.05 mm. The hydrochloride was prepared by saturating an ethereal solution with dry HCl gas and recrystallising the resultant solid from methanol-ether to give the hydrochloride of the title compound as colourless needles mpt. 173° C. Found: C, 58.2; H, 6.3; N, 6.3%. C11 H13 NO2.HCl requires C, 58.0; H, 6.2; N, 6.2%.
	With hydrogenchloride; lithium; phenyllithium In methanol; water	6.B B) B) Methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate A solution of 5,6,7,8-tetrahydroquinoline (14 g.) in dry ether (100 ml.) was added dropwise over one-half hour to an ethereal solution of phenyl lithium (prepared from bromobenzene (42 g.) and lithium (3.7 g.) in dry ether (300 ml.) and the reaction mixture stirred at room temperature for a further one hour. The cooled reaction mixture was saturated with dry CO2 gas, evaporated in vacuo and the residue treated with methanol previously saturated with dry HCl (500 ml.) and the solution heated at reflux for 12 hours. The solvent was removed in vacuo and the residue dissolved in water (50 ml.), extracted with ether (3 * 150 ml.) and the extracts discarded. The aqueous solution was made basic and extracted with ether (3 * 100 ml.). The combined ethereal extracts were dried, evaporated in vacuo and the residual oil distilled giving methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate as a colourless oil (13 g.) b.p. 92° C/0.05 mm. The hydrochloride was prepared by saturating an ethereal solution with dry HCl gas and recrystallising the resultant solid from methanol-ether to give the hydrochloride of the title compound as colourless needles mpt. 173° C. Found: C, 58.2; H, 6.3; N, 6.3%. C11 H13 NO2.HCl requires C, 58.0; H, 6.2; N, 6.2%.

	With hydrogenchloride; lithium; phenyllithium In methanol; water	6.B B. B. Methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate A solution of 5,6,7,8-tetrahydroquinoline (14 g.) in dry ether (100 ml.) was added dropwise over 1/2 hour to an ethereal solution of phenyl lithium (prepared from bromobenzene (42 g.) and lithium (3.7 g.) in dry ether (300 ml.) and the reaction mixture stirred at room temperature for a further one hour. The cooled reaction mixture was saturated with dry CO2 gas, evaporated in vacuo and the residue treated with methanol previously saturated with dry HCl (500 ml.) and the solution heated at reflux for 12 hours. The solvent was removed in vacuo and the residue dissolved in water (50 ml.), extracted with ether (3 * 150 ml.) and the extracts discarded. The aqueous solution was made basic and extracted with ether (3 * 100 ml.). The combined ethereal extracts were dried, evaporated in vacuo and the residual oil distilled giving methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate as a colourless oil (13 g.) b.p. 92° C/0.05 mm. The hydrochloride was prepared by saturating an ethereal solution with dry HCl gas and recrystallising the resultant solid from methanol-ether to give the hydrochloride of the title compound as colourless needles mpt. 173° C. Found: C, 58.2; H, 6.3; N, 6.3%. C11 H13 NO2.HCl requires C, 58.0; H, 6.2; N, 6.1%.
	With hydrogenchloride; lithium; phenyllithium In methanol; water	6.B B. B. Methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate A solution of 5,6,7,8-tetrahydroquinoline (14 g.) in dry ether (100 ml.) was added dropwise over 1/2 hour to an ethereal solution of phenyl lithium (prepared from bromobenzene (42 g.) and lithium (3.7 g.) in dry ether (300 ml.) and the reaction mixture stirred at room temperature for a further 1 hour. The cooled reaction mixture was saturated with dry CO2 gas, evaporated in vacuo and the residue treated with methanol previously saturated with dry HCl (500 ml.) and the solution heated at reflux for 12 hours. The solvent was removed in vacuo and the residue dissolved in water (50 ml.), extracted with ether (3 * 150 ml.) and the extracts discarded. The aqueous solution was made basic and extracted with ether (3 * 100 ml.). The combined ethereal extracts were dried, evaporated in vacuo and the residual oil distilled giving methyl-5,6,7,8-tetrahydroquinoline-8-carboxylate as a colourless oil (13 g.) b.p. 92° C/0.05 mm. The hydrochloride was prepared by saturating an ethereal solution with dry HCl gas and recrystallising the resultant solid from methanol-ether to give the hydrochloride of the title compound as colourless needles mpt. 173° C. Found: C, 58.2; H, 6.3; N, 6.3%. C11 H13 NO2.HCl requires C, 58.0; H, 6.2; N, 6.2%.

Reference： [1]Current Patent Assignee: PFIZER INC - US4009169, 1977, A
[2]Current Patent Assignee: PFIZER INC - US4011225, 1977, A
[3]Current Patent Assignee: PFIZER INC - US4031102, 1977, A
[4]Current Patent Assignee: PFIZER INC - US4044138, 1977, A
[5]Current Patent Assignee: PFIZER INC - US4085215, 1978, A

39
[ 75-15-0 ]
[ 10500-57-9 ]
[ 63757-94-8 ]
[ 74-88-4 ]
[ 53400-67-2 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; ammonia In methanol; hexane; water	37 3-Methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide EXAMPLE 37 3-Methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide To a solution of 3-methyl, 5,6,7,8-tetrahydroquinoline (10 g; 0.068 m.) in dry hexane (50 ml.) was added 50 ml. of a 15% solution of n-butyl lithium in hexane (0.09 m.) dropwise with stirring under an atmosphere of nitrogen. The dark red solution was stirred for 15 minutes at room temperature and then treated with carbon disulphide (10 ml.) The resulting pale yellow suspension was poured with water (100 ml.) and the aqueous solution was washed with ether (3 * 100 ml.). The aqueous solution of the lithium salt of 3-methyl-5,6,7,8-tetrahydroquinoline-8-dithiocarboxylic acid was stirred vigorously and methyl iodide (40 ml.) added. The solution was stirred at room temperature for 21/2 hours and extracted with ether (3 * 75 ml.). The ether solution was dried over anhydrous magnesium sulphate and evaporated. Methyl 3-methyl-5,6,7,8-tetrahydroquinoline-8-dithiocarboxylate was left as a red oil. The oil was dissolved in methanol previously saturated with ammonia (200 ml.) and the solution allowed to stand for 16 hours. The solvent was evaporated and the residue dissolved in ether (100 ml.). The ethereal solution was washed with water and the aqueous layer discarded. The solution was then extracted with 2N HCl (50 ml.) and water (50 ml.). The combined extracts were washed with ether and the pH of the solution adjusted to 9 with saturated sodium carbonate solution. The solution was extracted with ether (3 * 50 ml.) and the ethereal solution dried over anhydrous magnesium sulphate and evaporated to give the crude 3 -methyl-5,6,7,8-tetrahydroquinoline-8:thiocarboxamide (2.5 g.) tlc. on Silica gel F254 in ethyl acetate: Rf =0.4 and in ethanol Rf =0.8 identical with authentic material.
	With n-butyllithium; ammonia In methanol; hexane; water	37 3-Methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide EXAMPLE 37 3-Methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide To a solution of 3-methyl, 5,6,7,8-tetrahydroquinoline (10 g; 0.068 m.) in dry hexane (50 ml.) was added 50 ml. of a 15% solution of n-butyl lithium in hexane (0.09 m.) dropwise with stirring under an atmosphere of nitrogen. The dark red solution was stirred for 15 minutes at room temperature and then treated with carbon disulphide (10 ml.) The resulting pale yellow suspension was poured with water (100 ml.) and the aqueous solution was washed with ether (3 * 100 ml.). The aqueous solution of the lithium salt of 3-methyl-5,6,7,8-tetrahydroquinoline-8-dithiocarboxylic acid was stirred vigorously and methyl iodide (40 ml.) added. The solution was stirred at room temperature for 21/2 hours and extracted with ether (3 * 75 ml.). The ether solution was dried over anhydrous magnesium sulphate and evaporated. Methyl 3-methyl-5,6,7,8-tetrahydroquinoline-8-dithiocarboxylate was left as a red oil. The oil was dissolved in methanol previously saturated with ammonia (200 ml.) and the solution allowed to stand for 16 hours. The solvent was evaporated and the residue dissolved in ether (100 ml.). The ethereal solution was washed with water and the aqueous layer discarded. The solution was then extracted with 2N HCl (50 ml.) and water (50 ml.). The combined extracts were washed with ether and the pH of the solution adjusted to 9 with saturated sodium carbonate solution. The solution was extracted with ether (3 * 50 ml.) and the ethereal solution dried over anhydrous magnesium sulphate and evaporated to give the crude 3-methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide (2.5 g.) tlc. on Silica gel F254 ethyl acetate: Rf =0.4 and in ethanol Rf =0.8 identical with authentic material.

Reference： [1]Current Patent Assignee: PFIZER INC - US4031102, 1977, A
[2]Current Patent Assignee: PFIZER INC - US4085215, 1978, A

40
[ 10500-57-9 ]
5,6,7,8-tetrahydroquinoline-8-(N-lithio-N-trimethylsilyl) thiocarboxamide [ No CAS ]
5,6,7,8-tetrahydroquinoline-8-(N-trimethylsilyl)thiocarboxamide [ No CAS ]
[ 2290-65-5 ]
[ 108-18-9 ]
[ 53400-60-5 ]

Yield	Reaction Conditions	Operation in experiment
30%	With n-butyllithium In hexane; water; benzene	10 5,6,7,8-Tetrahydroquinoline-8-thiocarboxamide EXAMPLE 10 5,6,7,8-Tetrahydroquinoline-8-thiocarboxamide A solution of di-isopropylamine (33.3g, 0.33 mol) in benzene (150 ml) was cooled in ice and treated with 9% w/v butyl-lithium in hexane (237 ml, 0.33 mol). After 45 minutes the solution was treated with 5,6,7,8-tetrahydroquinoline (39.9 g, 0.3 mol) dropwise with stirring. After 1.5 hours trimethylsilyl-isothiocyanate (43.2 ml. 0.3 mol) was added and the resulting solution was allowed to stand at 0° C for 0.5 hours and at room temperature for 1 hour. Water (50 ml.) was added to the solution of 5,6,7,8-tetrahydroquinoline-8-(N-lithio-N-trimethylsilyl) thiocarboxamide causing hydrolysis to 5,6,7,8-tetrahydroquinoline-8-(N-trimethylsilyl)thiocarboxamide and subsequent hydrolysis to the title compound, and the resulting mixture acidified with 2N HCl. The acid solution was separated, washed with ethyl acetate and the pH was adjusted to 9 with solid sodium carbonate. Extraction with chloroform followed by drying of the extract over MgSO4, filtration and evaporation gave a thick gum which crystallized on trituration with n-hexane. Recrystallisation from methanol gave 5,6,7,8-tetrahydroquinoline-8-thiocarboxamide (16g, 30%) m.p. 160°. The hydrochloride was prepared by dissolution of the free base in hot isopropyl alcohol adding ethereal HCl solution and allowing to crystallise. m.p. 263°-4°. (Found: C, 52.6; H, 6.0; N, 12.2. C10 H12 N2 S, HCl requires C, 52.5; H, 5.7; N, 12.3%).

Reference： [1]Current Patent Assignee: PFIZER INC - US4085108, 1978, A

41
[ 10500-57-9 ]
[ 53400-60-5 ]
5,6,7,8-tetrahydro-8-lithioquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In hexane	12 8-Lithio-5,6,7,8-tetrahydroquinoline EXAMPLE 12 8-Lithio-5,6,7,8-tetrahydroquinoline The title compound is prepared using n-butyl lithium (9% w/v in hexane) and 5,6,7,8-tetrahydroquinoline by the general procedure of Example 7. The product may be converted to 5,6,7,8-tetrahydroquinoline-8-thiocarboxamide by the procedures described in Example 2 above, and U.S. Ser. No. 460,265.

Reference： [1]Current Patent Assignee: PFIZER INC - US4160094, 1979, A

42
[ 10500-57-9 ]
[ 369656-43-9 ]
(2S)-2-((1-methylimidazol-2-ylmethyl) aminomethyl) benzoylamino-5-(5,6,7,8-tetrahydro quinolyl-8-yl) aminovalerate 1-napthalenemethyleneamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Nα(1-methylimidazol-2-ylmethyl)aminomethylbenzoyl-Nδ-Boc-L-ornithine 1-naphthalene methyleneamide With hydrogenchloride In 1,4-dioxane; methanol at 20℃; for 2h; Stage #2: 5,6,7,8-tetrahydroquinoline With sodium cyanoborohydride; acetic acid; triethylamine In methanol at 20℃; Stage #3: With hydrogenchloride In water	81.4 In 4 ml of methanol, 0.19 g of the compound obtained in Synthesis Example 81-3 was dissolved. Then, 4 ml of a 4 mol/l hydrochloric acid/dioxane solution was dropped therein at room temperature and the whole was stirred for 2 hours without modification. The reaction solution was concentrated, and 0.20 g of a crude reaction product was obtained as a colorless oily product. This product and 0.05 g of 5,6,7,8-tetrahydroquinoline were dissolved in 4 ml of methanol, and then 0.08 g of triethylamine was dropped therein at room temperature. Acetic acid was added to the solution to adjust pH to about 4. Subsequently, 0.07 g of sodium cyanoborohydride was added to the solution and the whole was stirred overnight at room temperature. After that,thereaction solution was concentrated under reduced pressure. The residue was purified by means of silica gel column chromatography (9g, chloroform/methanol = 5/1) and was then treated with a 1 mol/l hydrochloric acid, consequently 0.07 g of hydrochloride of the above-mentioned compound was obtained as a white solid product. MS(FAB,Pos.):m/z=630[M+1]+1H-NMR(500MHz,DMSO-d6) : δ=1.73-1.84 (3H,brs),1.86-1.91 (3H,brs),1 .98 (1H,brs), 2.29 (1H,brs), 2.79 (2H,m), 2.95 (1H,brs), 3.08 (1H,m), 3 .97 (3H,s), 4.41 (3H,brs), 4.53-4.60 (3H,brs), 4.76 (2H,d), 7.37 (1H,m ), 7.46 (2H,d), 7.54 (2H,m), 7.67 (1H,d), 7.74 (2H,d), 7.76 (2H,d), 7.84 (1H,m), 7.94 (1H,m), 8.00 (2H,m), 8.07 (1H,m), 8.46 (1H,m), 8.69-8.74 (2H,m),9.14(1H,brs),10.73(1H,brs).

Reference： [1]Current Patent Assignee: KUREHA CORP. - EP1389460, 2004, A1 Location in patent: Page/Page column 95

43
[ 10500-57-9 ]
[ 556-96-7 ]
[ 1079883-82-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With di(rhodium)tetracarbonyl dichloride In 1,4-dioxane at 190℃; for 24h; Inert atmosphere;
76%	With di(rhodium)tetracarbonyl dichloride In 1,4-dioxane at 175 - 190℃; for 24h; Inert atmosphere; Sealed tube;

Reference： [1]Berman, Ashley M.; Lewis, Jared C.; Bergman, Robert G.; Ellman, Jonathan A. [Journal of the American Chemical Society, 2008, vol. 130, # 45, p. 14926 - 14927]
[2]Berman, Ashley M.; Bergman, Robert G.; Ellman, Jonathan A. [Journal of Organic Chemistry, 2010, vol. 75, # 22, p. 7863 - 7868]

44
[ 10500-57-9 ]
[ 78-82-0 ]
[ 1146576-65-9 ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: Isobutyronitrile In tetrahydrofuran at 20℃; for 3h; Stage #3: With sulfuric acid In tetrahydrofuran; water
42%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: Isobutyronitrile In tetrahydrofuran at 20℃; Inert atmosphere; Stage #3: With sulfuric acid; water In tetrahydrofuran

Reference： [1]Wang, Deping; Cai, Qian; Ding, Ke [Advanced Synthesis and Catalysis, 2009, vol. 351, # 11-12, p. 1722 - 1726]
[2]Wang, Deping; Ding, Ke [Chemical Communications, 2009, # 14, p. 1891 - 1893]

45
[ 10500-57-9 ]
[ 100-47-0 ]
5,6,7,8-tetrahydro-8-benzoylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: benzonitrile In tetrahydrofuran at 20℃; Inert atmosphere; Stage #3: With sulfuric acid; water In tetrahydrofuran

Reference： [1]Wang, Deping; Ding, Ke [Chemical Communications, 2009, # 14, p. 1891 - 1893]

46
[ 10500-57-9 ]
[ 75-05-8 ]
[ 1146576-61-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at 0℃; Inert atmosphere; Stage #2: acetonitrile In tetrahydrofuran at 20℃; Inert atmosphere; Stage #3: With sulfuric acid; water In tetrahydrofuran
	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at 0 - 5℃; for 1h; Stage #2: acetonitrile In tetrahydrofuran for 1h;	1.1-1.4 The preparation of its ligand is as follows: 1) 30g of 5,6,7,8-tetrahydroquinoline,THF450ml is placed in a 1000ml three-necked bottle and placed in the freezer,Stir and wait for the temperature to drop to around 0-5 , then start to add butyllithium dropwise (maintain below 0 during the process); 2) After dropping, keep the reaction for 1 hour, pour acetonitrile / THF, and react for another 1 hour; 3) Add 440ml of 3N hydrochloric acid and stir, the system is layered, and the water layer is adjusted to pH 7-8 with 5N NaOH.Extract the ethyl acetate layer 2-3 times and combine the organic layers; 4) Dry with MgSO4 and filter, the filtrate is concentrated to remove ethyl acetate, and the residual liquid is rectified with an oil pump.A light yellow oil was obtained.

Reference： [1]Wang, Deping; Ding, Ke [Chemical Communications, 2009, # 14, p. 1891 - 1893]
[2]Current Patent Assignee: RIZHAO BALUOTE PHARMACY - CN111099981, 2020, A Location in patent: Paragraph 0052-0056

47
[ 1227460-08-3 ]
[ 10500-57-9 ]
[ 1227461-26-8 ]

Yield	Reaction Conditions	Operation in experiment
19%	With hydrogen; acetic acid In tetrahydrofuran; ethanol at 20 - 60℃; for 23.5h;	2.1 Compound 2; (-Cyclohexylmethyl-^-dihydro-SH-pyrroloIS^-dlpyrimidin^-ylJ-quinolin-S-yl-amine; Step 1: (6,7-Dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-quinolin-3-yl-amine; [00400] A 50 mL flask was charged with (6-benzyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)- quinolin-3-yl-amine (60 mg, 0.17 mmol), ethanol (3 mL, 50 mmol) and acetic acid (0.05 mL, 0.9 mmol). Tetrahydrofuran (2 mL, 20 mmol) was added to the yellow suspension until the mixture clarified, followed by 20 wt% Palladium hydroxide on carbon (1 :4, Palladium hydroxide:carbon black, 12 mg, 0.017 mmol). The reaction flask was evacuated and flushed with hydrogen 3 times and the mixture hydrogenated at room temperature overnight. Aliquot after 21 h: LCMS showed <20% conversion, with the same apparent mixture of 2 reduction products seen in 424-126. The mixture was heated in an oil bath at 600C. Aliquot after 2.5 h; diluted with 5%MeCN in 1% aqueous HCO2H: LCMS showed separation of the undesired 5,6,7,8-tetrahydroquinoline [THQ] (13%; tR = 0.50 min) from desired amine (28%; tR = 0.45 min) with 65% SM/1,2,3,4-THQ remaining. The mixture was filtered through celite, concentrated to a yellow oil (crude 82 mg), and the residue purified by reverse-phase HPLC (10-75% ACN in 10 mM Et2NH/H2O) to afford (fl2) the secondary amine (8.5 mg, 19%) as a cream solid.

Reference： [1]Current Patent Assignee: EVOTEC AG - WO2010/59610, 2010, A1 Location in patent: Page/Page column 63

48
[ 10500-57-9 ]
[ 64-19-7 ]
[ 35149-14-5 ]

Yield	Reaction Conditions	Operation in experiment
88%	With copper(l) iodide; oxygen; palladium diacetate at 70℃; for 24h; Autoclave;

Reference： [1]Jiang, Huanfeng; Chen, Huoji; Wang, Azhong; Liu, Xiaohang [Chemical Communications, 2010, vol. 46, # 38, p. 7259 - 7261]

49
[ 10500-57-9 ]
[ 623-49-4 ]
[ 1350468-71-1 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 5,6,7,8-tetrahydroquinoline With N,N,N,N,-tetramethylethylenediamine; tert.-butyl lithium In 2-methyltetrahydrofuran; pentane Cooling with acetone-dry ice; Stage #2: ethyl cyanoformate In 2-methyltetrahydrofuran; pentane at 20℃; for 0.333333h; Cooling with acetone-dry ice;	9.A Step A: Diethyl 6,7-Dihvdroquinoline-8,8(5H)-dicarboxylate; To a solution of 5,6,7,8-tetrahydro-quinoline (370 mg, 2.78 mmol) in 2-MeTHF (6 mL), cooled in a dry ice/acetone bath, was added TMEDA (0.62 mL, 4.17 mmol) and ferf-butyllithium (2.45 mL, 4.17 mmol, 1.7 M in pentane), affording a dark brown solution. This solution was transferred to a separate flask, which contained a solution of ethyl cyanoformate (0.84 mL, 8.61 mmol) in 2-MeTHF (6 mL), also cooled in a dry ice/acetone bath. The reaction mixture was allowed to warm to room temperature, slowly. After 20 min., the reaction was quenched with water and then extracted with EtOAc. Brine was added to mitigate the formation of an emulsion. The organic layer was isolated, washed with 1 .0 M aq. HCI and brine, dried over Na2S04, and concentrated to dryness. The residue was purified by MPLC (gradient from pure heptane to 7:3 EtOAc/heptane) to give the title compound (555 mg, 72 % yield). LCMS (ESI) m/z: 278.2 [M+H] (100 %). 1H NMR (400 MHz, CDCI3) 5 1.26 (t, J=7.1 Hz, 6 H), 1 .77-1.86 (m, 2 H), 2.51-2.57 (m, 2 H), 2.84 (t, J=6.64 Hz, 2 H), 4.22-4.30 (m, 4 H), 7.12-7.15 (m, 1 H), 7.40-7.43 (m, 1 H), 8.43- 8.47 (m, 1 H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2011/145022, 2011, A1 Location in patent: Page/Page column 58-59

50
[ 10500-57-9 ]
[ 74-85-1 ]
[ 56717-33-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With (C₅Me₅)Sc(CH₂C₆H₄NMe₂-o)2; tris(pentafluorophenyl)borane In toluene at 70℃; for 36h;

Reference： [1]Guan, Bing-Tao; Hou, Zhaomin [Journal of the American Chemical Society, 2011, vol. 133, # 45, p. 18086 - 18089]

51
[ 10500-57-9 ]
[ 5787-31-5 ]
[ 1352745-21-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: s-butyl bromide In tetrahydrofuran; hexane at -78 - 20℃; for 1h;	1 Examplel8-sec-Butyl-5,6,7,8-tetrahydroquinoline (GR-50-0572); A solution of BuLi (6.8 ml, 1.6 M in hexane) was added dropwise to a cold (-78° C) solution of 5,6,7, 8-tetrahydroquinoline (1.33 g, 10 mmol) in THF (20 ml). The mixture was stirred for 10 min at -78° C and sec-butyl bromide (1.51g, 11 mmol) 5 was added dropwise. The mixture was allowed to warm up to room temperature during 1 h, was then carefully quenched with water and extracted with MTBE (3 x 50 ml). The combined organic phases were washed with water and brine, dried (MgS04) and concentrated in vacuo. The brown residue was distilled bulb-to-bulb to yield 1.69 g (89%) of the title compound as a colorless oil. This is a general 10 synthetic procedure and the other compounds exemplified were made according to this procedure, duly modified to employ the appropriate alkyl halide alkylating agent in order to add the correct alkyl group at the 8-position.Odor: green, herbaceous, American ginseng, ginger, tomato leaves, garden peas 2 Isomers in a ratio of 4:6.15 1H-NMR (300 MHz, CDCI3): 8.42-8.38 (m, 1 H), 7.30-7.27 (m, 1 H), 6.98-6.94 (m, 1 H), 3.05-2.45 (m, 4H), 2.05-1.85 (m, 2H), 1.68-1.52 (m, 2H), 1.51-1.28 (m, 1 H), 1.10-.097 (m, 4H (isomer A/B)), 0.78 (t, J = 7.2 Hz, 3/2H (Isomer A), 0.59 (d, J = 6.7 Hz, 3/2H (Isomer B)) ppm. 3C-NMR (75 MHz, CDCI3): 160.1 , 160.0 (s), 146.8, 146.6 (d), 136.2 (d), 133.4, 133.2 (s), 120.3, 120.2 (d), 46.4, 44.3 (d), 37.5, 27.1 (d),20 29.7, 29.6, 27.7, 24.6, 23.6, 22.5, 22.0, 21.8 (4t), 17.4, 14.1 (q), 12.5, 12.3 (q) ppm.GC/MS (El), major-isomer: 189 (M+, 14), 174 (74), 160 (23), 146 (25), 133 (100), 117 (23), 77 (6), 39 (4).
89%	With n-butyllithium In tetrahydrofuran; hexane	1 8-sec-Butyl-5,6,7,8-tetrahydroquinoline (GR-50-0572) EXAMPLE 1 8-sec-Butyl-5,6,7,8-tetrahydroquinoline (GR-50-0572) A solution of BuLi (6.8 ml, 1.6 M in hexane) was added dropwise to a cold (-78° C.) solution of 5,6,7,8-tetrahydroquinoline (1.33 g, 10 mmol) in THF (20 ml). The mixture was stirred for 10 min at -78° C. and sec-butyl bromide (1.51 g, 11 mmol) was added dropwise. The mixture was allowed to warm up to room temperature during 1 h, was then carefully quenched with water and extracted with MTBE (3*50 ml). The combined organic phases were washed with water and brine, dried (MgSO4) and concentrated in vacuo. The brown residue was distilled bulb-to-bulb to yield 1.69 g (89%) of the title compound as a colorless oil. This is a general synthetic procedure and the other compounds exemplified were made according to this procedure, duly modified to employ the appropriate alkyl halide alkylating agent in order to add the correct alkyl group at the 8-position. Odor: green, herbaceous, American ginseng, ginger, tomato leaves, garden peas 2 Isomers in a ratio of 4:6. 1H-NMR (300 MHz, CDCl3): 8.42-8.38 (m, 1H), 7.30-7.27 (m, 1H), 6.98-6.94 (m, 1H), 3.05-2.45 (m, 4H), 2.05-1.85 (m, 2H), 1.68-1.52 (m, 2H), 1.51-1.28 (m, 1H), 1.10-0.097 (m, 4H (isomer A/B)), 0.78 (t, J=7.2 Hz, 3/2H (Isomer A), 0.59 (d, J=206.7 Hz, 3/2H (Isomer B)) ppm. 13C-NMR (75 MHz, CDCl3): 160.1, 160.0 (s), 146.8, 146.6 (d), 136.2 (d), 133.4, 133.2 (s), 120.3, 120.2 (d), 46.4, 44.3 (d), 37.5, 27.1 (d), 29.7, 29.6, 27.7, 24.6, 23.6, 22.5, 22.0, 21.8 (4t), 17.4, 14.1 (q), 12.5, 12.3 (q) ppm. GC/MS (EI), major-isomer: 189 (M+, 14), 174 (74), 160 (23), 146 (25), 133 (100), 117 (23), 77 (6), 39 (4).

Reference： [1]Current Patent Assignee: GIVAUDAN SA - WO2011/160254, 2011, A1 Location in patent: Page/Page column 9-10
[2]Current Patent Assignee: GIVAUDAN SA - US2013/129655, 2013, A1 Location in patent: Page/Page column

52
[ 10500-57-9 ]
[ 82132-68-1 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 1722 - 1725
Angew. Chem.,2013,vol. 125,p. 1766 - 1769,4
[2]Patent: CN105884752,2016,A
[3]Chemistry - A European Journal,2017,vol. 23,p. 802 - 812

53
[ 10500-57-9 ]
[ 73183-34-3 ]
[ 1256360-50-5 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 75℃; for 11h; Inert atmosphere;
	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 75℃; for 11h; Inert atmosphere;	2.1 5,6,7,8-tetrahydroquinoline (2.0g, 15mmol), bis (1,5-cyclooctadiene) iridium two -μ- methoxybenzophenone (I) (297.4mg, 0.45mmol) , 4,4'-di-tert-butyl-2,2'-bipyridine (241mg, 0.9mmol) and bis(pinacolato)diboron (3.81g, 15mmol) in tetrahydrofuran was added to the lower (40 mL), the nitrogen 75 The reaction for 11 hours and concentrated to give the crude product (3.89 g of the), directly to the next reaction.
	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer In tetrahydrofuran at 75℃; for 11h;

Reference： [1]Zhao, Le; Tsukano, Chihiro; Kwon, Eunsang; Takemoto, Yoshiji; Hirama, Masahiro [Angewandte Chemie - International Edition, 2013, vol. 52, # 6, p. 1722 - 1725][Angew. Chem., 2013, vol. 125, # 6, p. 1766 - 1769,4]
[2]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884752, 2016, A Location in patent: Paragraph 0180; 0181; 0182
[3]Zhao, Le; Tsukano, Chihiro; Kwon, Eunsang; Shirakawa, Hisashi; Kaneko, Shuji; Takemoto, Yoshiji; Hirama, Masahiro [Chemistry - A European Journal, 2017, vol. 23, # 4, p. 802 - 812]

54
[ 10500-57-9 ]
(anti)-5,6,7,8-tetrahydroquinolin-8-yl{1-[3-(trifluoromethyl)phenyl]-cyclobutyl}methanol [ No CAS ]
(syn)-5,6,7,8-tetrahydroquinolin-8-yl{1-[3-(trifluoromethyl)phenyl]-cyclobutyl}methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at -78 - -20℃; for 0.5h; Inert atmosphere; Stage #2: In tetrahydrofuran at -20℃; for 1h;	179E; 180 Example 179E Example 179E (anti)-5,6,7,8-tetrahydroquinolin-8-yl{1-[3-(trifluoromethyl)phenyl]-cyclobutyl}methanol To a solution of 5,6,7,8-tetrahydroquinoline (233 mg, 1.753 mmol) in THF (10 mL) at -78° C. was added BuLi (1.315 mL, 2.103 mmol) under N2. The mixture was stirred at -20° C. for 30 minutes. A solution of Example 179D (400 mg, 1.753 mmol) in THF (5 mL) was added slowly and the mixture was warmed up to -20° C. for 60 minutes and then to room temperature. Saturated NH4Cl solution (60 mL) was added, then the mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by prep-HPLC (Column: Hanbon Benetnach C18 10 μm, 20*250 mm, eluent: water (10 mM NH4HCO3): acetonitrile, 55-85%) to afford Example 179E (80 mg, yield: 13%) and Example 180 (90 mg, yield: 15%). LC-MS: 362(M+H). 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.52 (s, 2H), 7.21-7.26 (m, 2H), 7.14 (d, J=7.6 Hz, 1H), 6.78 (t, J=6.2 Hz, 1H), 4.61 (d, J=7.6 Hz, 1H), 2.97-2.99 (m, 1H), 2.76-2.81 (m, 1H), 2.57-2.66 (m, 3H), 2.34-2.40 (m, 2H), 171-1.98 (m, 6H).

Reference： [1]Current Patent Assignee: ABBVIE INC - US2013/131036, 2013, A1 Location in patent: Paragraph 1818; 1819; 1820; 1821

55
[ 10500-57-9 ]
[ 1432492-71-1 ]
(anti)-5,6,7,8-tetrahydroquinolin-8-yl{1-[3-(trifluoromethyl)phenyl]-cyclobutyl}methanol [ No CAS ]
(syn)-5,6,7,8-tetrahydroquinolin-8-yl{1-[3-(trifluoromethyl)phenyl]-cyclobutyl}methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 13% 2: 15%	Stage #1: 5,6,7,8-tetrahydroquinoline With n-butyllithium In tetrahydrofuran at -78 - -20℃; for 0.5h; Inert atmosphere; Stage #2: 1-(3-(trifluoromethyl)phenyl)cyclobutanecarbaldehyde In tetrahydrofuran at -20 - 20℃; for 1h; Stage #3: Resolution of racemate;	179E; 180 (anti)-5,6,7,8-tetrahydroquinolin-8-yl{ 1-[3-(trifluoromethyl)phenyl]- cyclobutyl} methanol General procedure: (anti)-5,6,7,8-tetrahydroquinolin-8-yl{ l-[3-(trifluoromethyl)phenyl]- cyclobutyl} methanol[344] To a solution of 5,6,7, 8-tetrahydroquinoline (233 mg, 1.753 mmol) in THF (10 mL) at -78°C was added BuLi (1.315 mL, 2.103 mmol) under N2. The mixture was stirred at -20°C for 30 minutes. A solution of Example 179D (400 mg, 1.753 mmol) in THF (5 mL) was added slowly and the mixture was warmed up to -20°C for 60 minutes and then to room temperature. Saturated NH4C1 solution (60 mL) was added, then the mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with brine (50 mL), dried over a2S04, filtered and concentrated. The residue was purified by prep-HPLC (Column: Hanbon Benetnach CI 8 10 ???, 20x250 mm, eluent: water (10 mM NH4HCO3) : acetonitrile, 55-85%) to afford Example 179E (80 mg, yield: 13%) and Example 180 (90 mg, yield: 15%). LC-MS: 362(M+H). 'H NMR (400MHZ, CDCI3): ? 7.95 (s, 1H), 7.52 (s, 2H), 7.21-7.26 (m, 2H), 7.14 (d, J=7.6Hz, IH), 6.78 (t, J=6.2Hz, IH), 4.61 (d, J=7.6Hz, IH), 2.97-2.99 (m, IH), 2.76-2.81 (m, IH), 2.57-2.66 (m, 3H), 2.34-2.40 (m, 2H), 171-1.98 (m, 6H).

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2013/62966, 2013, A2 Location in patent: Paragraph 343; 344; 345; 346

56
[ 156-87-6 ]
[ 108-93-0 ]
[ 10500-57-9 ]

Yield	Reaction Conditions	Operation in experiment
62%	With C₄₂H₄₀N₂OP₂Ru; potassium <i>tert</i>-butylate In tetrahydrofuran; toluene for 72h; Inert atmosphere; Schlenk technique; Reflux;
53%	With (6-di-tert-butylphosphinomethyl-2,2’-bipyridyl)Ru(CO)HCl; potassium <i>tert</i>-butylate In tetrahydrofuran; toluene at 135℃; for 24h; Schlenk technique; Inert atmosphere; Glovebox;
48%	With potassium <i>tert</i>-butylate; C₄₅H₃₆ClNOP₂Ru In toluene at 110℃; for 24h; Inert atmosphere; Glovebox; Schlenk technique;

Reference： [1]Pan, Bing; Liu, Bo; Yue, Erlin; Liu, Qingbin; Yang, Xinzheng; Wang, Zheng; Sun, Wen-Hua [ACS Catalysis, 2016, vol. 6, # 2, p. 1247 - 1253]
[2]Srimani, Dipankar; Ben-David, Yehoshoa; Milstein, David [Chemical Communications, 2013, vol. 49, # 59, p. 6632 - 6634]
[3]Mondal, Rajarshi; Herbert, David E. [Organometallics, 2020, vol. 39, # 8, p. 1310 - 1317]

57
[ 91-22-5 ]
[ 10500-57-9 ]
[ 635-46-1 ]
[ 100-41-4 ]
[ 103-65-1 ]
[ 1821-39-2 ]
decahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With molybdenum(IV) disulfide; hydrogen In decane at 340℃;	3.1. Hydrodenitrogenation of quinoline Q was transformed rapidly during the early stages of the reac-tion. Fig. 2 shows the product distributions resulting from the HDNreaction of Q at 340C and 3 MPa of H2pressure. The HDN reac-tion of Q on the nanosized MoS2catalyst predominantly produced1,2,3,4-tetrahydroquinoline (THQ1) and hydrocarbons. The hydro-carbons detected were alkyl-benzene species, i.e., propylbenzene,ethylbenzene, isomers of dimethylbenzene, methyl-ethylbenzene,dimethyl-ethylbenzene, and methyl-propylbenzene. All the non-nitrogen containing products were effectively lumped together andsubsequently denoted herein as C9. More than 90% of Q was con-verted to THQ1 during the initial stages of the reaction, as shown inFig inFig. 2. Considerable amounts of ortho-propylaniline (OPA), 5,6,7,8-tetrahydroquinoline (THQ5) and decahydroquinoline (DHQ) werealso detected.

Reference： [1]Farag, Hamdy; Kishida, Masahiro; Al-Megren, Hamid [Applied Catalysis A: General, 2014, vol. 469, p. 173 - 182]

58
[ 10500-57-9 ]
[ 592-41-6 ]
2-(hexan-2-yl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With C₅₀H₆₃NO₂Zr; trityl tetrakis(pentafluorophenyl)borate In chlorobenzene at 100℃; for 24h; Inert atmosphere; Glovebox;
	With C₂₃H₂₉N₂Sc; triphenylcarbenium tetra(pentafluorophenyl)borate at 70℃; Schlenk technique; Inert atmosphere;

Reference： [1]Sun, Qiu; Chen, Ping; Wang, Yaorong; Luo, Yunjie; Yuan, Dan; Yao, Yingming [Inorganic Chemistry, 2018, vol. 57, # 18, p. 11788 - 11800]
[2]Song, Guoyong; O, Wylie W. N.; Hou, Zhaomin [Journal of the American Chemical Society, 2014, vol. 136, # 35, p. 12209 - 12212]

59
[ 10500-57-9 ]
[ 125163-08-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	With N-Bromosuccinimide; azobisisobutyronitrile In tetrachloromethane at 20℃; for 12h; Irradiation;	8-Bromo-5,6,7,8-tetrahydroquinoline (2x): General procedure: To a rt solution of 2-propylpyridine (2.5 g, 20.63 mmol) and (E)-2,2'-(diazene-1,2-diyl)bis(2-methylpropanenitrile)(1.253 g, 7.63 mmol) in CCl4 (60 mL) was added N-bromosuccinimide(1.933 mL, 22.69 mmol). The mixture was stirred under fluorescent light at rt for 12 h. The precipitates were filtered off through a pad of celite, washed with CCl4 (10 mL). The organic solutions were combined. After removal of the organic solvent under reduced pressure, purification of the residue by flash chromatography on silica gel with 0-20% EtOAc/Hexanes provided the title compound 2d as a pale yellow liquid (3.18 g, 77%).

Reference： [1]Yu, Ming; Stevenson, Karis; Zhou, Gene [Tetrahedron Letters, 2014, vol. 55, # 41, p. 5591 - 5594]

60
[ 108-94-1 ]
[ 109-76-2 ]
[ 10500-57-9 ]

Yield	Reaction Conditions	Operation in experiment
41%	With oxygen; copper diacetate; palladium diacetate In dimethyl sulfoxide at 120℃; for 23h;	5,6-Dihydrobenzo[h]quinoline⁸ (9) General procedure: Pd(OAc)2 (9.00 mg, 0.04 mmol) and () (14.6 mg, 0.08 mmol) were placed in a screw-top test tube, and a solution of 3,4-dihydronaphthalen-l(2H)-one (8) (58.6 mg, 0.40 mmol) in DMSO (0.08 mL) was added at room temperature. Then 1,3-diaminopropane (6) (0.10 mL, 1.20 mmol) was added to the reaction mixture. The test tube was filled with oxygen and then the resulting mixture was stirred at 120 °C for 16 h. After cooling down to room temperature, the palladium residue was removed by filtering through Celite. The organic solvent was removed under reduced pressure, and then the reaction was quenched by addition of 10% aqueous NH3 solution. The solution was extracted three times with a 4:1 mixture of hexane and EtOAc. The combined organic layers were washed with saturated aqueous NaCl solution, dried over anhydrous Na2S04, and filtered through Celite. The filtrate was concentrated to afford 5,6-dihydrobenzo[h]quinoline (9) (51.1 mg, 70%) as a yellow oil.
33%	With oxygen; copper(II) bis(trifluoromethanesulfonate); toluene-4-sulfonic acid In hexan-1-ol at 110℃; for 24h; Sealed tube; Schlenk technique;

Reference： [1]Mikami, Shunya; Toyota, Masahiro [Heterocycles, 2019, vol. 99, # 2, p. 1315 - 1321]
[2]Xi, Long-Yi; Zhang, Ruo-Yi; Liang, Shuai; Chen, Shan-Yong; Yu, Xiao-Qi [Organic Letters, 2014, vol. 16, # 20, p. 5269 - 5271]

61
[ 938-33-0 ]
[ 10500-57-9 ]
(+)-8-methoxy-5,6,7,8-tetrahydroquinoline [ No CAS ]
(-)-8-methoxy-5,6,7,8-tetrahydroquinoline [ No CAS ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 7558 - 7561

62
[ 6931-19-7 ]
[ 30389-37-8 ]
[ 10500-57-9 ]
(+)-5-methoxy-5,6,7,8-tetrahydroquinoline [ No CAS ]
(-)-5-methoxy-5,6,7,8-tetrahydroquinoline [ No CAS ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 7558 - 7561

63
[ 10500-57-9 ]
[ 5664-17-5 ]
C₁₈H₂₅N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With (C<SUB>5</SUB>Me<SUB>4</SUB>SiMe<SUB>3</SUB>)Sc(CH<SUB>2</SUB>C<SUB>6</SUB>H<SUB>4</SUB>NMe<SUB>2</SUB>-o)<SUB>2</SUB>; trityl tetrakis(pentafluorophenyl)borate In toluene at 70℃; for 24h; Glovebox; Schlenk technique; Sealed tube; stereoselective reaction;

Reference： [1]Song, Guoyong; Wang, Baoli; Nishiura, Masayoshi; Hou, Zhaomin [Chemistry - A European Journal, 2015, vol. 21, # 23, p. 8394 - 8398]

64
[ 10500-57-9 ]
[ 108-70-3 ]
3-(2,4,6-trichlorophenyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	With 1-Adamantanecarboxylic acid; oxygen; palladium diacetate; silver carbonate In N,N-dimethyl-formamide at 140℃; for 48h; regioselective reaction;

Reference： [1]He, Yongqin; Wu, Zhaoyang; Ma, Chaowei; Zhou, Xiaoqiang; Liu, Xingxing; Wang, Xiajun; Huang, Guosheng [Advanced Synthesis and Catalysis, 2016, vol. 358, # 3, p. 375 - 379]

65
[ 10500-57-9 ]
[ 106-46-7 ]
3-(2,5-dichlorophenyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With 1-Adamantanecarboxylic acid; oxygen; palladium diacetate; silver carbonate In N,N-dimethyl-formamide at 140℃; for 48h; regioselective reaction;

Reference： [1]He, Yongqin; Wu, Zhaoyang; Ma, Chaowei; Zhou, Xiaoqiang; Liu, Xingxing; Wang, Xiajun; Huang, Guosheng [Advanced Synthesis and Catalysis, 2016, vol. 358, # 3, p. 375 - 379]

66
[ 100-42-5 ]
[ 10500-57-9 ]
4-(1-phenylethyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: 5,6,7,8-tetrahydroquinoline With [2,2]bipyridinyl; chromium chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene; cyclohexylmagnesium bromide In tetrahydrofuran at 0℃; for 0.5h; Schlenk technique; Inert atmosphere; Stage #2: styrene In tetrahydrofuran at 80℃; for 48h; Schlenk technique; Inert atmosphere; regioselective reaction;
56 %Spectr.	With triethyl borane; sodium triethylborohydride In tetrahydrofuran at 140℃; for 12h; Inert atmosphere; regioselective reaction;

Reference： [1]Li, Yuexuan; Deng, Gongda; Zeng, Xiaoming [Organometallics, 2016, vol. 35, # 5, p. 747 - 750]
[2]Guan, Wei; Li, Runhan; Li, Xiaohong; Li, Yanfei; Wang, Ying; Xiong, Tao; Yin, Jianjun; Zhang, Ge; Zhang, Qian [Chemical Science, 2020, vol. 11, # 42, p. 11554 - 11561]

67
[ 10500-57-9 ]
[ 53400-41-2 ]

Yield	Reaction Conditions	Operation in experiment
77%	With tert.-butylhydroperoxide; manganese(II) triflate; In water; at 20℃; for 24h;	0.883 mg of Mn (OTf) 2 (0.5 mol%), 67 mg of 5,6,7,8-tetrahydroquinoline, 0.35 g of a 65% aqueous TBHP solution, 2.5 ml of water, was added in turn to a 25 mL round bottom flask, in the air at room temperature for 24 hours, the reaction solution was extracted with 3 x 5 mL of ethyl acetate, the ethyl acetate layer was collected, dried over anhydrous sodium sulfate, filtered, evaporation of ethyl acetate, petroleum ether and ethyl acetate (5: 1, v / v) as the eluent, the product 5,6,7,8-tetrahydroquinolin-5-one (56.6 mg) was isolated by silica gel column chromatography, light yellow liquid, yield 77%.

Reference： [1]Patent: CN105669548,2016,A .Location in patent: Paragraph 0029; 0030
[2]Chemical Communications,2019,vol. 55,p. 7840 - 7843

68
[ 10500-57-9 ]
[ 904929-24-4 ]

Reference： [1]Patent: CN105884752,2016,A

69
[ 10500-57-9 ]
[ 957-68-6 ]
C₁₇H₁₉N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 7-Aminocephalosporanic acid With chloro-trimethyl-silane; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane for 12h; Reflux; Large scale; Stage #2: With trimethylsilyl iodide; N,N-diethylaniline In dichloromethane at 18℃; for 3h; Large scale; Stage #3: 5,6,7,8-tetrahydroquinoline In dichloromethane; N,N-dimethyl acetamide for 6h; Large scale;	1 Example 1: Synthesis 7-ACQ dichloromethane 90KG (68L) + bis (trimethylsilyl) amine 19.5KG (25L) in 300L reaction vessel and stirred.Added 7-ACA25KG + trimethylchlorosilane 0.22KG (0.25L).Warmed to 58 ± 2 , stirred at reflux for 12 hours.Cooled to 5 ± 2 , added diethylaniline 25KG (27L), and mix well.Was added trimethylsilyl iodide 30KG (21.5L), stirred for 30 minutes.Warmed to 18 ± 2 , the reaction was stirred for 2.5 hours.Cooling to 8 ± 2 , tetrahydrofuran 4.5KG (5L), stirred for 30 minutes.Add tetrahydroquinoline 26KG (23L) + dimethylacetamide 47KG (50L), the reaction for 6 hours.The reaction was transferred into 500L reactor.Join dichloromethane 150KG (113L), and mix well.Cooled to 5 ± 2 , solution of isopropanol 25KG (32L).Petroleum ether was added dropwise 100KG (154L), stirred for 30 minutes.Filtered, washed with petroleum ether 20KG (30.5L) filtered three times to give a pale yellow solid.20wt% H was added to the 300L reaction vessel2SO460KG (55L).Was added to the pale yellow solid, 18 ± 2 under stirring to dissolve.Static stratification, from the aqueous phase.The solvent adding 20 water 5KG, stirred and extracted for 10 minutes.Still hierarchical, discard the solvent phase.The combined aqueous phase to the 300L reactor, cooled to 5 ± 2 , dropping 25% aqueous ammonia: 1st dropping 9KG (8L), seeded a little stirred crystallization 20 minutes; 2nd dropping 7KG (6.2L), stirred for 15 minutes crystallization; 3rd dropping 5KG (4.5L), stirred for 15 minutes crystallization;4th dropwise (about 3KG), adjusted pH = 2.9 ± 0.1, stirring was continued for 30 minutes crystallization; Solution of acetone 25KG (32L).Temperature 5 ± 2 , stirring raise grain for 1 hour.Filtered, washed with acetone 56KG (71L) + 20KG water mixture is washed and filtered.Then with acetone 20KG (25L) three times to wash the filter cake is set below 40 vacuum dried to give a pale yellow intermediate 7-ACQ35KG (relative to 7-ACA yield of about 1.4).

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN104031069, 2016, B Location in patent: Paragraph 0026-0032

70
[ 10500-57-9 ]
5,6,7,8-tetrahydro-4-(5,6,7,8-tetrahydroquinolin-4-yl)quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium at 110℃; for 24h;	4 0.1 mol of 5,6,7,8-tetrahydroquinoline and 0.025 mol of metallic sodium were added to the reaction flask,Heated to 110 ° C for 24 hours,After completion of the reaction,Cooled to room temperature, and the mixture poured into ice,So that the excess reaction of sodium metal is completed.Get oil-water mixture, oil-water separation.To the resulting oil was added anhydrous sodium sulfate,Standing overnightThe excess containing 5,6,7,8-tetrahydroquinoline was then removed by distillation under reduced pressure.The product obtained after steaming was recrystallized from the ethanol solution,To give a white or light yellow product,5,6,7,8-tetrahydro-4- (5,6,7,8-tetrahydroquinolin-4-y1) quinoline.0.02 mol of 5,6,7,8-tetrahydro-4- (5,6,7,8-tetrahydroquinolin-4-y1) quinoline was dissolved in 20 mL of acetonitrile solution,0.05 mol of bromo-octadecane was added,Reflux reaction 8h.After completion of the reaction, the resulting mixed solution was filtered,And the filter cake was dissolved in deionized water, lithium trifluoromethanesulfonyl chloride was added,A large amount of white precipitate appears.The white precipitate was filtered and recrystallized from absolute ethanol to give the product (having the chemical formula of the compound of Figure 1).

Reference： [1]Current Patent Assignee: HU SHANSHAN; NINGBO NINUO ELECTRONIC TECHNOLOGY CO LTD - CN104804720, 2017, B Location in patent: Paragraph 0046-0047

71
[ 100-42-5 ]
[ 10500-57-9 ]
C₁₇H₁₉N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium hexamethylsilazane In benzene at 80℃; for 60h; Schlenk technique; Sealed tube;

Reference： [1]Zhai, Dan-Dan; Zhang, Xiang-Yu; Liu, Yu-Feng; Zheng, Lei; Guan, Bing-Tao [Angewandte Chemie - International Edition, 2018, vol. 57, # 6, p. 1650 - 1653][Angew. Chem., 2018, vol. 130, # 6, p. 1666 - 1669,4]

72
[ 10500-57-9 ]
cinnamyl methyl carbonate [ No CAS ]
(R)-8-cinnamyl-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With (4S,5S)-1,3-bis(4-fluorophenyl)-4,5-diphenyl-2-[{(3R,3aS,6R,6aR)-6-(trityloxy)hexahydrofuro[3,2-b]furan-3-yl}oxy]-1,3,2-diazaphospholidine; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In acetonitrile at -15℃; for 36h; Glovebox; Inert atmosphere; enantioselective reaction;

Reference： [1]Murakami, Ryo; Sano, Kentaro; Iwai, Tomohiro; Taniguchi, Tohru; Monde, Kenji; Sawamura, Masaya [Angewandte Chemie - International Edition, 2018, vol. 57, # 30, p. 9465 - 9469][Angew. Chem., 2018, vol. 130, p. 9609 - 9613,5]

73
[ 10500-57-9 ]
[ 488151-80-0 ]
(R,E)-8-(3-(4-methoxyphenyl)allyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With (4S,5S)-1,3-bis(4-fluorophenyl)-4,5-diphenyl-2-[{(3R,3aS,6R,6aR)-6-(trityloxy)hexahydrofuro[3,2-b]furan-3-yl}oxy]-1,3,2-diazaphospholidine; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In acetonitrile at -20℃; for 36h; Glovebox; Inert atmosphere; enantioselective reaction;

Reference： [1]Murakami, Ryo; Sano, Kentaro; Iwai, Tomohiro; Taniguchi, Tohru; Monde, Kenji; Sawamura, Masaya [Angewandte Chemie - International Edition, 2018, vol. 57, # 30, p. 9465 - 9469][Angew. Chem., 2018, vol. 130, p. 9609 - 9613,5]

74
[ 10500-57-9 ]
[ 776296-20-9 ]
(R,E)-8-(3-(benzo[d][1,3]dioxol-5-yl)allyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With (4S,5S)-1,3-bis(4-fluorophenyl)-4,5-diphenyl-2-[{(3R,3aS,6R,6aR)-6-(trityloxy)hexahydrofuro[3,2-b]furan-3-yl}oxy]-1,3,2-diazaphospholidine; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In acetonitrile at -20℃; for 36h; Glovebox; Inert atmosphere; enantioselective reaction;

Reference： [1]Murakami, Ryo; Sano, Kentaro; Iwai, Tomohiro; Taniguchi, Tohru; Monde, Kenji; Sawamura, Masaya [Angewandte Chemie - International Edition, 2018, vol. 57, # 30, p. 9465 - 9469][Angew. Chem., 2018, vol. 130, p. 9609 - 9613,5]

75
[ 10500-57-9 ]
[ 1315566-28-9 ]
(R,E)-8-(3-(3-bromophenyl)allyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With (4S,5S)-1,3-bis(4-fluorophenyl)-4,5-diphenyl-2-[{(3R,3aS,6R,6aR)-6-(trityloxy)hexahydrofuro[3,2-b]furan-3-yl}oxy]-1,3,2-diazaphospholidine; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In acetonitrile at -20℃; for 36h; Glovebox; Inert atmosphere; enantioselective reaction;

Reference： [1]Murakami, Ryo; Sano, Kentaro; Iwai, Tomohiro; Taniguchi, Tohru; Monde, Kenji; Sawamura, Masaya [Angewandte Chemie - International Edition, 2018, vol. 57, # 30, p. 9465 - 9469][Angew. Chem., 2018, vol. 130, p. 9609 - 9613,5]

76
[ 10500-57-9 ]
[ 67046-22-4 ]

Reference： [1]Patent: EP1726590,2006,A1

77
[ 10500-57-9 ]
[ 26726-16-9 ]
(5-bromofuran-2-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With aluminum (III) chloride In dichloromethane at 0℃; for 0.333333h;	1.3 3,Synthesis of (5-bromofuran-2-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone Compound 3 (2.66 g, 19.97 mmol)And 5-bromofuran-2-carbonyl chloride (4.18 g, 19.97 mmol) was dissolved in CH2Cl2 (30 mL).Anhydrous AlCl3 (8.0 g, 60 mmol) was added portionwise over 5 min.The reaction mixture was stirred at 0 °C for 15 min and quenched by slowly adding ice at 0 °C.The mixture was diluted with water and then extracted with ethyl acetate (150 mL), and organic layer and water layer were separated.The aqueous layer was washed with additional EtOAc (EtOAc) (EtOAc)EtOAc.The filtrate was concentrated in vacuo to give a white solid which was crystallised from CH3OH (10 mg/mL).Obtaining a white crystalline solid (5-bromofuran-2-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone (Compound 4),4.34 g, 71% yield.

Reference： [1]Current Patent Assignee: Wang Ping - CN108929318, 2018, A Location in patent: Paragraph 0025; 0032; 0033; 0034

78
[ 110-86-1 ]
[ 110-56-5 ]
[ 10500-57-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With aluminum (III) chloride at 25℃; for 24h; Inert atmosphere;	1.2 2, Synthesis of 5,6,7,8-tetrahydroquinoline At 25 ° C and an inert atmosphere,Compound 2 (2.67 g, 21.02 mmol) was added to a suspension of aluminum chloride (0.20 g, 1.5 mmol) in pyridine (10 mL).After stirring the obtained orange solution for 24 hours,It was poured into an ice water mixture (50 g) and extracted with ethyl acetate (50 mL).The organic layer was separated and washed sequentially with water (50 mL).The organic layer was washed with saturated sodium bicarbonate solution (50 mL) and brine (50 mL).It was then dried over NaSO4 and concentrated in vacuo.The yellow oil was subjected to flash chromatography on silica gel (eluent: hexane),Obtaining 5,6,7,8-tetrahydroquinoline (compound 3),2.66 g, yield 95%.
95%	With aluminum (III) chloride for 24h;	1.2 2, Synthesis of 5,6,7,8-tetrahydroquinoline Compound 2 (2.67 g, 21.02 mmol) was added to a suspension of aluminum chloride (0.20 g, 1.5 mmol) in pyridine (10 mL). After stirring the obtained orange solution for 24 hours, It was poured into an ice water mixture (50 g) and extracted with ethyl acetate (50 mL). The organic layer was separated and washed sequentially with water (50 mL). The organic layer was washed with saturated sodium bicarbonate solution (50 mL) and brine (50 mL). It was then dried over NaSO4 and concentrated in vacuo. The obtained yellow oil was purified by flash chromatography on silica gel (eluent:hexane). 5,6,7,8-tetrahydroquinoline (compound 3), 2.66 g, The yield was 95%.
95%	With aluminum (III) chloride for 24h;	1.2 2,Synthesis of 5,6,7,8-tetrahydroquinoline Compound 2 (2.67 g, 21.02 mmol) was added to a suspension of aluminum chloride (0.20 g, 1.5 mmol) in pyridine (10 mL).After the resulting orange solution was stirred for 24 hours, poured into ice-water mixture (50 g) and ethyl acetate (50mL).The organic layer was separated, and then organic layer was washed with water (50mL), sat. sodium hydrogen carbonate (50mL) and brine (50mL).It was then dried over NaSO4 and concentrated in vacuo.The obtained yellow oil was purified by flash chromatography on silica gel (eluent:hexane).5,6,7,8-tetrahydroquinoline (Compound 3) was obtained, 2.66 g, yield 95%.

Reference： [1]Current Patent Assignee: Wang Ping - CN108929318, 2018, A Location in patent: Paragraph 0025; 0029; 0030; 0031
[2]Current Patent Assignee: Wang Ping - CN108947969, 2018, A Location in patent: Paragraph 0028-0030
[3]Current Patent Assignee: Wang Ping - CN109305937, 2019, A Location in patent: Paragraph 0024; 0028-0030

79
[ 10500-57-9 ]
[ 2388-32-1 ]
(2-chloro-quinolin-4-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With aluminum (III) chloride In dichloromethane at 0℃;	1.3 Synthesis of (2-chloro-quinolin-4-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone Compound 3 (2.66 g, 19.97 mmol) and 2-chloro-quinoline-4-carbonyl chloride (19.97 mmol) were dissolved in CH2Cl2 (30 mL) It was cooled to 0 ° C using an ice salt bath. Anhydrous AlCl3 (8.0 g, 60 mmol) was added portionwise over 5 min. The reaction mixture was stirred at 0 °C for 15 min and quenched by slowly adding ice at 0 °C. The mixture was diluted with water and then extracted with ethyl acetate (150 mL). The organic layer and the aqueous layer are separated. The aqueous layer was washed with additional ethyl acetate (150 mL). The combined organic layers were washed sequentially with water (2OmL) and brine (50 mL) and dried over Na2SO. The filtrate was concentrated in vacuo to give a white solid. It was recrystallized from CH3OH (10 mg/mL). Obtaining a white crystalline solid (2-chloro-quinolin-4-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone (Compound 4), 4.19g, The yield was 65%.
65%	With aluminum (III) chloride In dichloromethane at 0℃; for 0.333333h;	1.3 3,Synthesis of (2-Chloro-quinolin-4-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone Compound 3 (2.66 g, 19.97 mmol) and 2-chloro-quinoline-4-carbonyl chloride (19.97 mmol) were dissolved in CH 2Cl 2 (30 mL).Anhydrous AlCl3 (8.0 g, 60 mmol) was added portionwise over 5 min. The reaction mixture was stirred at 0 °C for 15 min and quenched by slowly adding ice at 0 °C.The mixture was diluted with water and then extracted with ethyl acetate (150 mL), and organic layer and water layer were separated.The aqueous layer was washed with additional ethyl acetate (150 mL).The combined organic layers were washed sequentially with water (2OmL) and brine (50 mL) and dried over Na2SO.The filtrate was concentrated in vacuo to give a white solid.It was recrystallized from CH3OH (10 mg/mL).Obtained as a white crystalline solid (2-chloro-quinolin-4-yl)(5,6,7,8-tetrahydroquinolin-3-yl)methanone (Compound 4), 4.19 g,The yield was 65%.

Reference： [1]Current Patent Assignee: Wang Ping - CN108947969, 2018, A Location in patent: Paragraph 0031-0033
[2]Current Patent Assignee: Wang Ping - CN109305937, 2019, A Location in patent: Paragraph 0024; 0031-0033

80
[ 10500-57-9 ]
[ 62-23-7 ]
5,6,7,8-tetrahydroquinolin-8-yl 4-nitrobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With oxygen; copper(I) bromide In chlorobenzene at 130℃; for 30h; Schlenk technique; Sealed tube; Green chemistry;

Reference： [1]Cheng, Li; Sun, Yuqian; Wang, Wenrong; Yao, Changsheng; Li, Tuan-Jie [Journal of Organic Chemistry, 2019, vol. 84, # 6, p. 3074 - 3082]

81
[ 10500-57-9 ]
[ 104-15-4 ]
[ 957-68-6 ]
C₁₇H₂₀N₃O₃S⁽¹⁺⁾*C₇H₇O₃S^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22 g	Stage #1: 7-Aminocephalosporanic acid With iodine; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane at 0 - 45℃; for 5h; Stage #2: With trimethylsilyl iodide; triethylamine In dichloromethane at 0 - 10℃; for 4h; Stage #3: 5,6,7,8-tetrahydroquinoline; toluene-4-sulfonic acid Further stages;	3 Put 27.2 g of 7-ACA into 150 ml of dichloromethane, lower the temperature to 0 to 5 ° C, and add 30 ml of N, N-hexamethyldisilazane and 0.1 g of iodine. The feed liquid was then heated to 45 ° C. and refluxed for 5 hours. The temperature of the feed liquid is lowered to 0-10 ° C, 15 ml of triethylamine and 40 g of trimethyliodosilane are added, and the reaction is kept for 4 hours. Then, 25 g of 5,6,7,8-tetrahydroquinoline was added to the feed liquid, and the reaction was held for 15 hours. Then, 800 ml of n-butane was added dropwise to the material solution, and a solid was gradually precipitated. After stirring for 60 minutes, filtration was performed, and an appropriate amount of n-butane was washed. Drain.The obtained solid is added to 120 ml of water, about 20 g of p-toluenesulfonic acid is added, the pH of the feed liquid is adjusted to about 3.0 to 3.5, and the solid is dissolved. Then, 5 g of activated carbon was added, the mixture was decolorized by stirring for 30 minutes, and then filtered. The obtained filtrate was added dropwise to 1200 ml of acetone, a solid was precipitated, stirred for 30 minutes, and filtered, washed with an appropriate amount of acetone, dried by suction, and dried in a vacuum drying box at 40 ° C. to obtain p-methylbenzenesulfonate of the compound represented by formula Approximately 22 g of acid salt, 95% product purity, molecular structure is as follows:

Reference： [1]Current Patent Assignee: QILU SYNVA PHARMACEUTICAL CO LTD - CN110294770, 2019, A Location in patent: Paragraph 0096-0101

82
[ 10500-57-9 ]
[ 957-68-6 ]
C₁₇H₂₀N₃O₃S⁽¹⁺⁾*Cl^(1-)*ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28 g	Stage #1: 7-Aminocephalosporanic acid With triethylamine In dichloromethane at 0 - 5℃; for 1h; Stage #2: With chloro-trimethyl-silane In dichloromethane at 0 - 5℃; for 2.5h; Stage #3: 5,6,7,8-tetrahydroquinoline Further stages;	1 Put 27.2g of 7-ACA into 150ml of dichloromethane and lower the temperature to 0 5 50 ml of triethylamine was added dropwise over 60 minutes. After the dropwise addition was completed, 27 g of trimethylchlorosilane was added dropwise to the feed solution. The dropwise addition was completed in 90 minutes. The temperature was maintained at 0-5 ° C for 60 minutes. The solids were removed by filtration and 50 ml was used. Wash with dichloromethane and combine the filtrates;(2) The combined filtrate was cooled to -10 to -5 ° C, 15 ml of triethylamine and 50 g of trimethyliodosilane were added, and the reaction was maintained at 0 to 10 ° C for 3 hours.(3) Then, 25 g of 5,6,7,8-tetrahydroquinoline was added to the feed liquid, and the reaction was held for 12 hours. Then, 800 ml of isopropanol was added dropwise to the material solution, and a solid was gradually precipitated. After stirring for 60 minutes, the mixture was filtered and washed with isopropanol. Drain.(4) The obtained solid was added to 100 ml of water, 30 ml of concentrated hydrochloric acid was added, the solid was dissolved, and then 5 g of activated carbon was added, and the mixture was decolorized by stirring for 30 minutes, and then filtered. The obtained filtrate was added dropwise to 1000 ml of isopropyl alcohol, a solid was precipitated, stirred for 30 minutes, and then filtered, washed with an appropriate amount of isopropyl alcohol, drained, and dried in a vacuum drying box at 40 ° C to obtain two compounds of the formula I The hydrochloride is about 28g, the purity of the product is 96%, and the molecular structure is as follows:

Reference： [1]Current Patent Assignee: QILU SYNVA PHARMACEUTICAL CO LTD - CN110294770, 2019, A Location in patent: Paragraph 0083-0088

83
[ 10500-57-9 ]
[ 957-68-6 ]
C₁₇H₂₀N₃O₃S⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26 g	Stage #1: 7-Aminocephalosporanic acid With iodine; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane at 0 - 45℃; for 5h; Stage #2: With trimethylsilyl iodide; triethylamine In dichloromethane at 0 - 10℃; for 4h; Stage #3: 5,6,7,8-tetrahydroquinoline Further stages;	2 Put 27.2g of 7-ACA into 150ml of dichloromethane and lower the temperature to 0 5 .30 ml of N, N-hexamethyldisilazane and 0.1 g of iodine were added, and then the feed liquid was heated to 45 ° C. and refluxed for 5 hours. The temperature of the feed liquid is lowered to 0-10 ° C, 15 ml of triethylamine and 40 g of trimethyliodosilane are added, and the reaction is kept for 4 hours.Then, 25 g of 5,6,7,8-tetrahydroquinoline was added to the feed liquid, and the reaction was held for 15 hours. Then, 800 ml of isopropanol was added dropwise to the material solution, and a solid was gradually precipitated. After stirring for 60 minutes, the mixture was filtered and washed with an appropriate amount of isopropanol. Drain. The obtained solid is added to 100 ml of water, about 10 ml of concentrated hydrochloric acid is added, the pH of the feed liquid is adjusted to about 3.5, and the solid is dissolved. Then, 5 g of activated carbon was added, the mixture was decolorized by stirring for 30 minutes, and then filtered. The obtained filtrate was added dropwise to 800 ml of acetone, a solid was precipitated, stirred for 30 minutes, and filtered, washed with an appropriate amount of acetone, dried by suction, and dried in a vacuum drying box at 40 ° C. to obtain a monohydrochloride salt of the compound of formula I 26g, product purity 96.8%, molecular structure is as follows:

Reference： [1]Current Patent Assignee: QILU SYNVA PHARMACEUTICAL CO LTD - CN110294770, 2019, A Location in patent: Paragraph 0089-0095

84
[ 10500-57-9 ]
[ 169772-25-2 ]
N-(tert-butyl)-5,6,7,8-tetrahydroquinoline-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; tetraethylammonium tosylate In acetonitrile Schlenk technique; Inert atmosphere; Electrochemical reaction; Irradiation; Sealed tube;

Reference： [1]Lai, Xiao-Li; Shu, Xiao-Min; Song, Jinshuai; Xu, Hai-Chao [Angewandte Chemie - International Edition, 2020, vol. 59, # 26, p. 10626 - 10632][Angew. Chem., 2020, vol. 132, # 26, p. 10713 - 10719,7]

85
[ 10500-57-9 ]
8-oximino-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With tert.-butylnitrite; <i>tert</i>-butyl alcohol at 50℃; for 0.166667h; Flow reactor; UV-irradiation;	General procedure for the synthesis of additional oxime compounds 10-17. General procedure: A stock solution comprising of t-BuONO (25 mmol), t-BuOH (20 equiv.) and starting material(20 equiv.) was pumped through the photoreactor (365 nm, 50 °C internal temperature) at 1mL/min passing through a 10 mL FEP reactor coil (10 min residence time). A 40 psi backpressure regulator was positioned at the exit of the reactor maintaining in a fixed systempressure. The reactor output was collected as a batch and stirred with activated charcoal (2g) for 1 h, filtered and volatiles removed by evaporation under reduced pressure. Theproduct was purified by column chromatography followed by recrystallisation of thematerial from an appropriate solvent.

Reference： [1]Griffiths, Oliver M.; Ruggeri, Michele; Baxendale, Ian R. [Synlett, 2020, vol. 31, # 19, p. 1907 - 1912]

86
[ 10500-57-9 ]
8-fluoro-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With sodium hydrogencarbonate; Selectfluor In acetonitrile at 20℃; for 20h; Inert atmosphere;	Fluorinated Nitrogen Heterocycles 2a-f; General Procedure A(GP A) General procedure: To an oven-dried flask (under N2) was added NaHCO3 (0.750 mmol, 2equiv) followed by the co-addition over 4 h of a solution of 1a-f(0.375 mmol, 1 equiv) and a solution of Selectfluor (0.375 mmol, 1equiv) in dry CH3CN (1.5 mL, [0.25 M]). The mixture was then stirred for 16 h at r.t. gradually forming an orange brown solution. The mixture was diluted with CH2Cl2, washed with sat. NaHCO3 soln and extracted with CH2Cl2. The combined organic layers were dried(MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, petroleum ether/EtOAc100:0 to 95:5) to give the product.

Reference： [1]Le Guen, Clothilde; Mazzah, Ahmed; Penhoat, Maël; Melnyk, Patricia; Rolando, Christian; Chausset-Boissarie, Laëtitia [Synthesis, 2021, vol. 53, # 6, p. 1157 - 1162]

87
[ 10500-57-9 ]
C₉H₁₀⁽²⁾HN [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5,6,7,8-tetrahydroquinoline With bis(2,2,6,6-tetramethyl-1-piperidyl)zinc In 1,4-dioxane; toluene at 80℃; for 0.533333h; Inert atmosphere; Sealed tube; Stage #2: With water-d2 for 0.0833333h;	General Procedure C: (condition A) General procedure: A flame-dried microwave vial equipped with a magnetic stir bar was evacuated and backfilled withN2 (this process was repeated three times). To the reaction vessel was added a solution of starting material2 (0.1mmol, 1 equiv.) in anhydrous 1,4-dioxane (0.1 M, 1 mL), followed by the solution of commercialZn(TMP)2 (0.3 mL, 0.5M in toulene, 0.15 mmol, 1.5 equiv). The reaction was stirred at differenttemperature for 2 h as the table shows.Immediately after removal from heat, the reaction was quenched with D2O (0.5 mL) and stirredfor 5 minutes to cool down to room temperature. A solution of internal standard 1,3,5-trimethoxybenzenein EtOAc was added (0.33 mmol unless otherwise stated) before extraction with EtOAc (4 x 1.5 mL), andthe combined organic extracts were dried with Na2SO4 and filtered through a short silica plug and washedwith EtOAc (5 mL) and concentrated under reduced pressure by rotary evaporation. Then 0.2 mL of CDCl3 was added and the excess solvent was removed under vacuum. Finally, the deuteration and degradationpercentage was determined by crude 1H NMR based on the internal standard.

Reference： [1]Zhang, Pengpeng; Cantrell, Rachel L.; Newhouse, Timothy R. [Synlett, 2021, vol. 32, # 16, p. 1652 - 1656]

88
[ 10500-57-9 ]
(difluoromethyl)bis(4-methoxyphenyl)phosphine [ No CAS ]
4-(difluoromethyl)-5,6,7,8-tetrahydroquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: 5,6,7,8-tetrahydroquinoline; (difluoromethyl)bis(4-methoxyphenyl)phosphine With trifluoromethylsulfonic anhydride In dichloromethane at -78℃; for 0.583333h; Inert atmosphere; Stage #2: With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #3: With hydrogenchloride In 1,4-dioxane; ethanol; lithium hydroxide monohydrate at 40℃; for 24h;	5 General Procedure A. General procedure: An oven dried 8 mL vial or 25 mL round bottom flask was charged with the heterocycle (1.0 equiv) and phosphine (1.1 equiv) and placed under a nitrogen atmosphere. CH2Q2 (0.1 M) was added, the reaction vessel cooled to -78 °C and Tf2O (1.0 equiv) was added dropwise over 5 minutes. The reaction was stirred for 30 minutes before DBU (1.0 equiv) was added dropwise (note - addition should be performed with vigorous stirring to ensure the DBU is readily homogenized; at -78 °C it tends to freeze and stick to the stir bar, preventing stirring). After the addition was complete, the reaction was warmed to 0 °C in an ice bath over 5 minutes. A 10 % H2O in EtOH (v/v) solution was added to the reaction, bringing the final concentration to 0.05 M, and HCI in dioxane was added (1.0 equiv). The reaction was heated to 40 °C and allowed to run for 24 h, then quenched with a saturated aqueous solution of NaHCO; and the aqueous layer was extracted with CH2Q2 (3x). The combined organic extracts were washed with a saturated aqueous solution of brine, dried (MgSCL), filtered, and con WceOinr 2a0ie2u2/0 tn87 v1a2c9uo. The residue was puri .f.i.ed , , by f „lash ■ co ,fumn ch ■ roma ,tograp PnyCT io/U pSru20vi2u1e/0 u5i5e842 difluoromethylated heteroarene

Reference： [1]Current Patent Assignee: COLORADO STATE UNIVERSITY SYSTEM - WO2022/87129, 2022, A1 Location in patent: Page/Page column 20; 61-62; 66

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CAS No. :	10500-57-9	MDL No. :	MFCD00006734
Formula :	C₉H₁₁N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YQDGQEKUTLYWJU-UHFFFAOYSA-N
M.W :	133.19	Pubchem ID :	66335
Synonyms :

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.44
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	41.67
TPSA :	12.89 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.64 cm/s

Log Po/w (iLOGP) :	1.9
Log Po/w (XLOGP3) :	2.08
Log Po/w (WLOGP) :	1.96
Log Po/w (MLOGP) :	1.8
Log Po/w (SILICOS-IT) :	2.92
Consensus Log Po/w :	2.13

[ CAS No. 10500-57-9 ] {[proInfo.proName]}

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[ 10500-57-9 ] Synthesis Path-Upstream 1~8

[ 10500-57-9 ] Synthesis Path-Downstream 1~88

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[ 10500-57-9 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.42
Solubility :	0.506 mg/ml ; 0.0038 mol/l
Class :	Soluble
Log S (Ali) :	-1.98
Solubility :	1.39 mg/ml ; 0.0105 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.1
Solubility :	0.106 mg/ml ; 0.000796 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.84

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

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

[ CAS No. 10500-57-9 ] {[proInfo.proName]}

Quality Control of [ 10500-57-9 ]

Related Doc. of [ 10500-57-9 ]

Product Details of [ 10500-57-9 ]

Calculated chemistry of [ 10500-57-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 10500-57-9 ]

Application In Synthesis of [ 10500-57-9 ]

[ 10500-57-9 ] Synthesis Path-Upstream 1~8

[ 10500-57-9 ] Synthesis Path-Downstream 1~88

Related Parent Nucleus of [ 10500-57-9 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Parent Nucleus of
[ 10500-57-9 ]