* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With tetrahydroxydiboron; copper diacetate In acetonitrile at 40℃; for 12 h;
6-chloroquinoline (0.3 mmol, 49 mg)Tetrahydroxy diboron (0.9mmol, 81mg),Cu (OAc) 2 (0.015 mmol, 2.5 mg) was added to 1 mL of acetonitrile,40 ° C for 12 hours,The residue was purified by thin layer chromatography to give 47.6 mg of 6-chloro tetrahydroquinoline in 95percent yield, 98percent purity,
84%
With tetrahydroxydiboron; copper diacetate In acetonitrile at 40℃; for 8 h; Schlenk technique
General procedure: A 20 mL Schlenk tube was charged with quinoline (1a; 65 mg,0.5 mmol), Cu(OAc)2 (4.5 mg, 0.025 mmol), B2(OH)4 (135 mg,1.5 mmol), and MeCN (2.0 mL). The mixture was stirred at 40 °C for 8 h until the reaction was completed (TLC), then cooled to room temperature and concentrated under reduced pressure. Water (10 mL) was added and the mixture was extracted with EtOAc (3 x 10 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with petroleum ether/ethyl acetate (8:1) as an eluent to give a brown liquid (2a: 65 mg, 98percent yield).
83%
With palladium; hydrogen In acetonitrile at 30℃; for 16 h;
To a solution of PdNPore (2.7 mg, 5 molpercent) in acetonitrile (5 mL) was added the substrate 6-chloroquinoline(81.8 mg, 0.5 mmol), hydrogen (5 bar), placed on a magnetic stirrer at 30 ° C for 16 h, column chromatography (silica gel, 200-300Methyl acetate) to give 6-chloro-1,2,3,4-tetrahydroquinoline 69.57 mg in 83percent yield,
79%
With ethanol; Dimethylphenylsilane; Au-TiO2 In neat (no solvent) at 70℃; for 3 h;
General procedure: To a dry vial containing 8-methoxyquinoline, 1 (0.048 g, 0.3 mmol), Me2PhSiH (185 μL, 1.2mmol) and ethanol (70 μL, 1.2 mmol), Au/TiO2 (60 mg, 1.0 molpercent) was added. The Au contentin catalyst was ~1 wtpercent. The mixture was heated to 70 oC and the progress of reaction wasmonitored by TLC and GC. After 15 min (100percent conversion), ethanol (1 mL) was added and theresulting slurry was filtered under reduced pressure through a short pad of silica gel with the aidof ethanol (2-3 mL) to withhold the supported catalyst. The filtrate was evaporated undervacuum and the residue was chromatographed (n-hexane/ethyl acetate, 10:1) to afford 8-methoxy-1,2,3,4-tetrahydroquinoline (1a) (41 mg, 84percent yield).
78%
Stage #1: With hydrogenchloride; hydrogen In ethanol; water at 20℃; Stage #2: With sodium hydrogencarbonate In water
To a solution of 6-chloroquinoline (1.5 g, 9.17 mmol) in C2H5OH (50 ml) was added Pt02 (41.5 mg, 0.18 mmol) and concentrated HC1 (0.1 ml) under an atmosphere of hydrogen gas. The reaction was stirred overnight at room temperature, then concentrated in vacuo, diluted with water (100 ml), adjusted to pH 8 with aqueous sodium bicarbonate. The resulting solution was extracted with dichloromethane (3 x 80 ml) and the organic layers were combined, dried over anhydrous magnesium sulfate, concentrated in vacuo to afford 6-chloro-l,2,3,4- tetrahydroquinoline as a colorless oil (1.2 g, 78 ).LC/MS (ES, m/z) [M+H]+ 168.0'H-NMR (300 MHz, CDCI3) δ 6.90 - 6.98 (m, 2H), 6.39 - 6.42 (t, / = 1.2 Hz, 1H), 3.23 - 3.35 (m, 2H), 2.73 - 2.81 (m, 2H), 1.91 - 1.96 (m, 2H)
62%
With hydrogen In methanol for 4 h;
A flask filled with a mixture of 6-chloroquinoline (12.0 g, 73.3 mmol), PtO2 (2.16 g, 13 mol percent), and MeOH (500 mL, 6.15 M) was flushed with N2 and then equipped with a balloon filled with H2. The reaction was kept under H2 atmosphere and stirred for 4 h. The mixture was filtered through Celite and washed with CH2Cl2. Purification via silica gel chromatography using 50percent CH2Cl2 in hexanes gave 6-chloro-1,2,3,4-tetrahydroquinoline (7.7 g, 62percent). 1H NMR (400 MHz, DMSO-d6) δ 6.85-6.83 (m, 2H), 6.42-6.39 (m, 1H), 5.82 (s, 1H), 3.17-3.13 (m, 2H), 2.64 (t, J=6.3 Hz, 2H), 1.78-1.72 (m, 2H). LC/MS (10percent-99percent CH3CN (0.035percent TFA)/H2O (0.05percent TFA)), m/z: M+1 obs=168.2; tR=1.57 min.
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8
[ 612-57-7 ]
[ 635-46-1 ]
[ 49716-18-9 ]
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[2] Molecular Catalysis, 2018, vol. 452, p. 145 - 153
Reference:
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[2] Journal of Materials Chemistry A, 2017, vol. 5, # 7, p. 3260 - 3266
With Tris(3,6-dioxaheptyl)amine; sodium nitrite In <i>tert</i>-butyl alcohol at 130℃; for 24 h; Inert atmosphere
EXAMPLE FIFTY-FOUR: General Procdure for Pd-Catalyzed Nitrations of Aryl Chlorides and Aryl Sulfonates (Figures 20 and 21); An oven-dried schlenk tube, which was equipped with a magnetic stir bar and fitted with a rubber septum, was charged with the Pd2(dba)3 (0.5 mol percent), ligand (6, 25, 26, or 27) (1.2 mol percent), and NaNO2 (138 mg, 2.0 mmol) (aryl halides* that were solids at room <n="146"/>temperature were added with the catalyst). The vessel was evacuated and backfilled with argon (this process was repeated a total of 3 times) and then the aryl halide* (1.0 mmol), tris(3,6-dioxaheptyl)amine (5 mol percent), and te/t-butanol (2 mL) were added via syringe. The reaction vessel was sealed with a Teflon screw cap and heated to 110 0C for 24 h. The solution was cooled to room temperature, diluted with Ethyl acetate, washed with water, and purified via flash chromatography.* Includes aryltriflates and arylnonaflates.
Reference:
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[2] Journal of the American Chemical Society, 2009, vol. 131, # 36, p. 12898 - 12899
13
[ 60-35-5 ]
[ 612-57-7 ]
[ 22433-76-7 ]
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14
[ 67-56-1 ]
[ 612-57-7 ]
[ 201230-82-2 ]
[ 38896-30-9 ]
Reference:
[1] Journal of Organic Chemistry, 2008, vol. 73, # 18, p. 7096 - 7101
15
[ 612-57-7 ]
[ 59394-30-8 ]
Reference:
[1] Patent: US4461896, 1984, A,
16
[ 612-57-7 ]
[ 64-17-5 ]
[ 201230-82-2 ]
[ 73987-38-9 ]
Reference:
[1] Journal of Organic Chemistry, 2008, vol. 73, # 18, p. 7096 - 7101
17
[ 612-57-7 ]
[ 86984-32-9 ]
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[4] Patent: EP418071, 1991, A2,
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With tetrachloromethane; iron(III) chloride hexahydrate; at 150℃; for 8h;Inert atmosphere; Sealed tube;
General procedure: An ampule was charged with 0.02 mmol of FeCl3·6H2O, 2 mmol of aniline, 4 mmol of carbon tetrachloride, and 8 mmol 1,3-propanediol under argon. The sealed ampule was placed into a pressure reactor, which was hermetically closed and heated at 150C for 8 h with continuous stirring. After the reaction completion, the reactor was cooled to room temperature, the ampule was opened, the reaction mixture was poured in hydrochloric acid. The aqueous layer was separated, neutralized with 10% sodium hydroxide solution, and extracted with methylenechloride. The organic layer was filtered, the solvent was distilled off, and the residue was distilled in a vacuum. Physicochemical characteristics and spectral data of the obtained compounds 2a-2l corresponded to the literature data.
With N-Bromosuccinimide; In acetic acid; at 70 - 115℃; for 3.5h;
A slurry of of <strong>[612-57-7]6-chloroquinoline</strong> (50 g, 306 mmol) and NBS (59.8 g, 336 mmol) inAcOH (500 ml.) was heated at 1 15 C for 90 min, then was allowed to cool to roomtemperature. More NBS (0.25 eq. 15 g) was added and the reaction mixture was heated at 70 C for 2 h. The resulting mixture was allowed to cool to room temperature and wasconcentrated. The residue was taken up into water (500 ml_). The resulting slurry was filtered, solid washed with water. The solid was dissolved in CH2CI2 (500 ml_). The layers were separated. The organic layer was concentrated and purified by multiple column chromatography (0-40% CH2CI2/hexane) and triturations using CH2CI2 to obtain 3-bromo-<strong>[612-57-7]6-chloroquinoline</strong> (45.2 g, 61 .0 % yield) as an off-white solid: 1 H NMR (400 MHz, DMSO-d6) delta ppm 7.80 (dd, 1 H) 8.03 (d, J=9.07 Hz, 1 H) 8.08 (d, J=2.34 Hz, 1 H) 8.69 (d, J=2.24 Hz, 1 H) 8.96 (d, J=2.24 Hz, 1 H); ES LC-MS m/z =242.1 (Br79, CI35 M+H)+.
With N-Bromosuccinimide; In dichloromethane; cyclohexane; water; acetic acid;
4.1 3-Bromo-<strong>[612-57-7]6-chloroquinoline</strong>. 4.8 g (29 mmol) of <strong>[612-57-7]6-chloroquinoline</strong>, in solution in 50 ml of acetic acid, are introduced into a 100 ml three-necked round-bottomed flask, after which 5.75 g (32 mmol) of N-bromosuccinimide are added and the mixture is heated at 100 C. for 6 h. The reaction mixture is poured into 100 ml of water and the whole is extracted with dichloromethane. The pooled organic phases are dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography on a silica gel column, with the elution being carried out using a 50/50, and then a 30/70, mixture of cyclohexane and dichloromethane. 4.86 g of product are obtained. Melting point: 110-111 C.
The synthesis was done by the same procedure as that of J. J. Eisch (J. Org. Chem. Vol. 27, p.1318, 1962). Bromine (79 mul) and carbon tetrachloride (2 ml) were added to <strong>[612-57-7]6-chloroquinoline</strong> (250 mg) and stirred at 90C for two hours. Pyridine (123 mul) was added to the reaction solution and stirred at the same temperature for 16 hours. The reaction solution was concentrated and purified with a silica gel chromatography (hexane - ethyl acetate) to obtain the title compound (250 mg).
To a solution of <strong>[612-57-7]6-chloro-quinoline</strong> (2.08 g, 12.3 mmol) in tetrahydrofuran (50 mL) was added [1- (6-METHYL-PYRIDIN-2-YL)-ETHANONE] (2.0 g, 14.8 mmol, 1.1 equiv), palladium acetate (0.055 g, 0.25 mmol, 0.02 equiv), 2- dicyclohexylphosphino-2'- (N, N-dimethylamino) biphenyl (0.197 g, 0.50 mmol, 0.04 equiv), and potassium [TERT-BUTOXIDE] (3.76 g, 30.75 mmol, 2.2 equiv). The resulting reaction mixture was heated to [80C] for 18 hours, then cooled down to [20C,] and slowly treated with acetic acid (3 mL). The resulting solids were filtered off, and the mother liquor was concentrated in vacuo. Silica gel chromatography (3: 1 [HEXANE/ACETONE)] yielded [1- (6-METHYL-PYRIDIN-2-YL)-2-QUINOLIN-6-YL-ETHANONE] (2.52 g, [ 78%).
75%
With potassium tert-butylate; palladium diacetate; DavePhos; In tetrahydrofuran; at 75℃; for 14h;
To a solution of <strong>[612-57-7]6-chloroquinoline</strong> (12.24 mmol) in tetrahydrofuran (50 mL), 1-(6-methylpyridin-2-yl)ethanone (12.24 mmol), palladium(II) acetate (0.24 mmol), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (0.49 mmol), and potassium tert-butoxide (26.92 mmol) were added. The resulting mixture was heated to 75 C for 14 h. After cooled to room temperature, the reaction mixture was slowly quenched with acetic acid (3 mL). The mixture was filtered through a celite pad and washed with EtOAc (50 mL). The filtrate was evaporated to dryness under reduced pressure, and the residue was purified by MPLC on silica gel using and EtOAc/hexane (1:1) as eluent to give the titled compound as an off-white solid. Yield 75%; 1H NMR (CDCl3) delta 2.68 (s, 3H), 4.75 (s, 2H), 7.34 (dd, 1H, J = 7.6, 0.4 Hz), 7.40 (dd, 1H, J = 8.2, 4.2 Hz), 7.71 (t, 1H, J = 7.6 Hz), 7.76 (dd, 1H, J = 8.8, 2.0 Hz), 7.80 (d, 1H, J = 2.0 Hz), 7.87 (br d, 1H, J = 7.6 Hz), 8.11 (d, 1H, J = 8.8 Hz), 8.15 (br d, 1H, J = 8.2 Hz), 8.88 (dd, 1H, J = 4.2, 1.8 Hz).
(+-) 3-(6-Quinolinyl)-9-methyl-3,9-diazabicyclo-[4.2.1]-nonane Fumaric Acid Salt (A2) Was prepared according to Method A, using <strong>[612-57-7]6-chloroquinoline</strong> as starting material and palladacycle [Angew. Chem. Int. Ed. Engl. 1995 34 1844], palladium acetate and 2-biphenyl-di-tert-butylphosphine as catalysts. Mp. 164-166 C.
Step 1 1-(Benzoyl)-6-chloro-1,2-dihydro-quinoline-2-carbonitrile A solution of <strong>[612-57-7]6-chloroquinoline</strong> (9.5 g), benzoyl chloride (13.2 g) in methylene chloride (50 mL) was treated with AlCl3 (0.10 g) followed by dropwise addition of trimethyl silyl cyanide (12.5 mL). After 0.5 hour, the mixture was diluted with 150 mL of methylene chloride and washed with water, 1N HCl, saturated sodium bicarbonate (aq.), and brine. The organic phase was dried over magnesium sulfate then evaporated to dryness. The residue was purified by column chromatography on silica gel using ethyl acetate/hexane (3:7) as the eluding solvent. The title compound (13 g) was obtained as a white solid, m.p. 141-143 C. This product was used for the preparation of the title compound described in step 2.
EXAMPLE 8 6-Chloro-1-hydroxyquinol-2(1H)-one Using the method of Example 1, but using <strong>[612-57-7]6-chloroquinoline</strong> the desired compound was obtained. Melting Point: 175-177 C. IR (KBr): 1640, 1625, 1420, 820, 812. Mass Spectrum: 195, 197 (M+); 178, 150, 138, 123, 114
EXAMPLE 33 6-Chloro-2-quinolinecarboxylic Acid By substituting <strong>[612-57-7]6-chloroquinoline</strong> (75 g) for the 6-methylquinoline in the procedure of Example 28, 1-benzoyl-2-cyano-1,2-dihydro-<strong>[612-57-7]6-chloroquinoline</strong>; yield 98 g, m.p. 140-143, and 6-chloro-2-quinolinecarboxylic acid; yield 51.5 g, m.p. 231-232 (dec) were obtained.
With sodium hydroxide; potassium carbonate; sodium thiosulfate; 3-chloro-benzenecarboperoxoic acid; In dichloromethane;
[Referential Example 250] 6-Chloro-2-cyanoquinoline: <strong>[612-57-7]6-Chloroquinoline</strong> (2.50 g) was dissolved in dichloromethane (25 ml), and m-chloroperbenzoic acid (3.71 g) was added under ice cooling to stir the mixture at room temperature for 1 hour. After the reaction mixture was diluted with dichloromethane, the diluted mixture was washed with an aqueous solution of sodium thiosulfate and an aqueous solution of sodium hydroxide and dried over anhydrous sodium sulfate. The solvent wasdistilled off under reduced pressure, and the residue was dissolved in dichloromethane (40 ml), and trimethylsilyl cyanide (2.0 ml) and N,N-dimethylcarbamoyl chloride (1.50 ml) were added to heat the resultant mixture for 9 hours under reflux. After trimethylsilyl cyanide (2,0 ml) and N,N-dimethylcarbamoyl chloride (1.50 ml) were additionally added, and the mixture was heated for 16 hours under reflux, the reaction mixture was diluted with dichloromethane, and a 10% aqueous solution (40 ml) of potassium carbonate was added to stir the mixture for 30 minutes. After an organic layer was separated and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. Dichloromethane was added to the residue, and crystals deposited were collected by filtration to obtain the title compound (1.77 g) as colorless crystals. Further, a mother liquor was purified by column chromatography on silica gel (dichloromethane) to obtain the title compound (0.80 g) as pale yellow crystals. 1H-NMR (DMSO-d6) delta: 7.94(1H,dd,J=9.0,2.2Hz), 8.09(1H,d,J=8.5Hz), 8.15(1H,d,J=9.0Hz), 8.29(1H,d,J=2.2Hz), 8.63(1H,d,J=8.5Hz). MS (FAB) m/z: 189(M+H)+.
With sodium hydroxide; potassium carbonate; sodium thiosulfate; 3-chloro-benzenecarboperoxoic acid; In dichloromethane;
REFERENTIAL EXAMPLE 53 6-Chloro-2-quinolinecarbonitrile: <strong>[612-57-7]6-Chloroquinoline</strong> (2.50 g) was dissolved in methylene chloride (25 ml), and m-chloroperbenzoic acid (3.71 g) was added under ice cooling to stir the mixture at room temperature for 1 hour. After the reaction mixture was diluted with methylene chloride, the diluted mixture was washed with an aqueous solution of sodium thiosulfate and an aqueous solution of sodium hydroxide and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was dissolved in methylene chloride (40 ml), and trimethylsilyl cyanide (2.0 ml) and N,N-dimethylcarbamoyl chloride (1.50 ml) were added to heat the resultant mixture for 9 hours under reflux. After trimethylsilyl cyanide (1.0 ml) and N,N-dimethylcarbamoyl chloride (0.80 ml) were additionally added, and the mixture was heated for 16 hours under reflux, the reaction mixture was diluted with methylene chloride, and a 10% aqueous solution (40 ml) of potassium carbonate was added to stir the mixture for 30 minutes. After an organic layer was separated and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. Methylene chloride was added to the residue, and crystals deposited were collected by filtration to obtain the title compound (1.77 g). Further, a mother liquor was purified by column chromatography on silica gel (methylene chloride) to obtain the title compound (0.80 g). 1H-NMR (DMSO-d6) delta: 7.94(1H,dd,J=9.0, 2.2 Hz), 8.09(1H,d,J=8.5 Hz), 8.15(1H,d,J=9.0 Hz), 8.29(1H,d,J=2.2 Hz), 8.63(1H,d,J=8.5 Hz). MS (FAB) m/z: 189(M+H)+.
With potassium tert-butylate; acetic acid;palladium diacetate; In tetrahydrofuran;
Step C Preparation of 1-(6-Methyl-pyridin-2-yl)-2-quinolin-6-yl-ethanone To a solution of <strong>[612-57-7]6-chloro-quinoline</strong> (2.08 g, 12.3 mmol) in tetrahydrofuran (50 mL) was added 1-(6-methyl-pyridin-2-yl)-ethanone of Step B (2.0 g, 14.8 mmol, 1.1 equiv), palladium acetate (0.055 g, 0.25 mmol, 0.02 equiv), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (0.197 g, 0.50 mmol, 0.04 equiv), and potassium tert-butoxide (3.76 g, 30.75 mmol, 2.2 equiv). The resulting reaction mixture was heated to 80 C. for 18 hours, then cooled down to 20 C., and slowly treated with acetic acid (3 mL). The resulting solids were filtered off, and the mother liquor was concentrated in vacuo. Silica gel chromatography (3:1 hexane/acetone) yielded the title compound (2.52 g, 78%).
With water; potassium carbonate;palladium diacetate; dicyclohexyl-(2?,4?,6?-triisopropyl-3,6-dimethoxy-[1,1?-biphenyl]-2-yl)phosphine; In tert-butyl alcohol; at 110℃; for 1h;Inert atmosphere;
EXAMPLE FIVE: General Procedure for Cross-Coupling Reactions of Heteroarylamines; An oven-dried test tube, which was equipped with a magnetic stir bar and fitted with a Teflon screw cap septum, was charged with Pd(OAc)2 (0.01 mmol) and 1 (0.03 mmol). The vessel was evacuated and backfilled with argon (this process was repeated a total of 3 times) and then t-BuOH (2 mL) and degassed H2O (0.04 mmol) were added via syringe. After addition of the water the solution was heated to 80 0C for 1 minute.A second oven-dried reaction vessel, which was equipped with a magnetic stir bar and fitted with a Teflon screw cap septum, was charged with K2Ctheta3 (1.4 mmol). The vessel was evacuated and backfilled with argon (this process was repeated a total of 3 times) and then the aryl chloride (1.0 mmol) and amine (1.2 mmol) were added via syringe (aryl chlorides or amines that were solids at room temperature were added with the base) and the activated catalyst solution was transferred from the first reaction vessel via cannula. The solution was heated to 110 0C until the starting material had been completely consumed as monitored by GC. The reaction was then cooled to room temperature, diluted with EtOAc, washed with water, concentrated in vacuo, and purified via the Biotage SP4 (silica-packed 25+M cartridge).
With Tris(3,6-dioxaheptyl)amine; sodium nitrite;tris-(dibenzylideneacetone)dipalladium(0); t-BuBrettPhos; In tert-butyl alcohol; at 130℃; for 24h;Inert atmosphere;Product distribution / selectivity;
EXAMPLE FIFTY-FOUR: General Procdure for Pd-Catalyzed Nitrations of Aryl Chlorides and Aryl Sulfonates (Figures 20 and 21); An oven-dried schlenk tube, which was equipped with a magnetic stir bar and fitted with a rubber septum, was charged with the Pd2(dba)3 (0.5 mol %), ligand (6, 25, 26, or 27) (1.2 mol %), and NaNO2 (138 mg, 2.0 mmol) (aryl halides* that were solids at room <n="146"/>temperature were added with the catalyst). The vessel was evacuated and backfilled with argon (this process was repeated a total of 3 times) and then the aryl halide* (1.0 mmol), tris(3,6-dioxaheptyl)amine (5 mol %), and te/t-butanol (2 mL) were added via syringe. The reaction vessel was sealed with a Teflon screw cap and heated to 110 0C for 24 h. The solution was cooled to room temperature, diluted with Ethyl acetate, washed with water, and purified via flash chromatography.* Includes aryltriflates and arylnonaflates.