* 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.
Reference：
[1] Russian Journal of General Chemistry, 2010, vol. 80, # 9, p. 1891 - 1893
7
[ 140367-36-8 ]
[ 826-85-7 ]
[ 791-28-6 ]
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1991, vol. 61, # 11, p. 2419 - 2420[2] Zhurnal Obshchei Khimii, 1991, vol. 61, # 11, p. 2607 - 2608
8
[ 50-00-0 ]
[ 76097-73-9 ]
[ 67927-44-0 ]
[ 76088-29-4 ]
[ 791-28-6 ]
Reference：
[1] Chemistry of Natural Compounds, 1980, vol. 16, # 4, p. 403 - 405[2] Khimiya Prirodnykh Soedinenii, 1980, vol. 16, # 4, p. 553 - 556
9
[ 76097-73-9 ]
[ 70439-29-1 ]
[ 67927-44-0 ]
[ 791-28-6 ]
Reference：
[1] Chemistry of Natural Compounds, 1980, vol. 16, # 4, p. 403 - 405[2] Khimiya Prirodnykh Soedinenii, 1980, vol. 16, # 4, p. 553 - 556
10
[ 2387-23-7 ]
[ 603-35-0 ]
[ 538-75-0 ]
[ 791-28-6 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 1, p. 373 - 376
[2] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 1, p. 373 - 376
11
[ 1212-29-9 ]
[ 603-35-0 ]
[ 538-75-0 ]
[ 791-28-6 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 1, p. 373 - 376
12
[ 29393-95-1 ]
[ 762-21-0 ]
[ 791-28-6 ]
Reference：
[1] Tetrahedron Letters, 1993, vol. 34, # 35, p. 5621 - 5622
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 17, p. 2467 - 2472
13
[ 74255-73-5 ]
[ 791-28-6 ]
[ 3060-50-2 ]
Reference：
[1] J. Gen. Chem. USSR (Engl. Transl.), 1980, vol. 50, # 1, p. 42 - 45[2] Zhurnal Obshchei Khimii, 1980, vol. 50, # 1, p. 52 - 55
14
[ 106-23-0 ]
[ 791-28-6 ]
[ 2051-18-5 ]
Reference：
[1] Patent: US4002769, 1977, A,
15
[ 72050-06-7 ]
[ 371-42-6 ]
[ 3878-45-3 ]
[ 791-28-6 ]
Reference：
[1] Journal of Organic Chemistry, 1980, vol. 45, # 2, p. 271 - 273
16
[ 117199-32-3 ]
[ 7726-95-6 ]
[ 79384-10-4 ]
[ 24169-93-5 ]
[ 754-10-9 ]
[ 7440-57-5 ]
[ 791-28-6 ]
Reference：
[1] Journal of General Chemistry USSR (English Translation), 1988, vol. 58, p. 54 - 61[2] Zhurnal Obshchei Khimii, 1988, vol. 58, p. 62 - 71
17
[ 82208-51-3 ]
[ 603-35-0 ]
[ 2483-57-0 ]
[ 791-28-6 ]
Reference：
[1] Journal of Organic Chemistry USSR (English Translation), 1984, vol. 20, # 8, p. 1571 - 1573[2] Zhurnal Organicheskoi Khimii, 1984, vol. 20, # 8, p. 1724 - 1727
18
[ 5182-44-5 ]
[ 16799-05-6 ]
[ 791-28-6 ]
Yield
Reaction Conditions
Operation in experiment
57%
With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃; for 18 h;
To a solution of 2- (3-chlorophenyl) ethanol (1.06 g, 6.0 mmol) in CH2CL2 (50 mL) at RT under nitrogen was added CBr4 (1.98 g, 5.8 mmol) and PPh3 (1.57 g, 5.8 mmol). After stirring at RT for 18 h the reaction mixture was concentrated and the residue diluted with ETZO (30 mL) resulting in precipitation of triphenylphosphine oxide. The ethereal solution was decanted, evaporated and purified via flash chromatography (silica, hexane) to provide 2- (3-CHLORO) phenylethyl bromide as a clear oil (57percent). 1H NMR (400 MHz, DMSO-d6) 8 7.39-7. 22 (m, 3 H), 7.18-7. 09 (m, 1 H), 3.63-3. 51 (m, 2 H), 3.25-3. 17 (m, 2 H); 13C NMR (100.6 MHz, DMSO-d6) B 141.2, 134.6, 130.7, 129.3, 127.6, 127.3.
Reference：
[1] Journal of Organometallic Chemistry, 1980, vol. 185, # 2, p. 283 - 296
22
[ 108-86-1 ]
[ 14311-22-9 ]
[ 2751-90-8 ]
[ 3878-45-3 ]
[ 791-28-6 ]
Reference：
[1] Journal of Organometallic Chemistry, 1980, vol. 185, # 2, p. 283 - 296
23
[ 108-86-1 ]
[ 1079-66-9 ]
[ 1707-03-5 ]
[ 2751-90-8 ]
[ 791-28-6 ]
Reference：
[1] Journal of Organometallic Chemistry, 1980, vol. 185, # 2, p. 283 - 296
24
[ 791-28-6 ]
[ 2001-45-8 ]
[ 603-35-0 ]
Reference：
[1] Chemical Communications, 2018, vol. 54, # 46, p. 5843 - 5846
[2] Chemical Communications, 2018, vol. 54, # 46, p. 5843 - 5846
25
[ 591-51-5 ]
[ 791-28-6 ]
[ 2001-45-8 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1949, vol. 562, p. 187,190, 192
26
[ 74650-72-9 ]
[ 791-28-6 ]
[ 74650-73-0 ]
Yield
Reaction Conditions
Operation in experiment
86%
With trifluoromethylsulfonic anhydride In dichloromethane
(E) Preparation of 2-chloro-5-methoxynicotinonitrile Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2 Cl2 (50 mL) and the mixture cooled to 0°-4° C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2 Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2 CO3 solution and extracted with CHCl3 (2*). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86percent) of 2-chloro-5-methoxynicotinonitrile 1 H NMR (CDCl3) δ3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm- 1.
86%
With trifluoromethylsulfonic anhydride In dichloromethane
(E) Preparation of 2-chloro-5-methoxynicotinonitrile Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2 Cl2 (50 mL) and the mixture cooled to 0°-4° C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2 Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2 CO3 solution and extracted with CHCl3 (2X). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86percent) of 2-chloro-5-methoxynicotinonitrile 1 H NMR (CDCl3) δ 3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm-1.
Reference：
[1] Patent: US4329351, 1982, A,
[2] Patent: US4374140, 1983, A,
ethyl (2Z)-3-[6-(benzyloxy)pyridin-3-yl]-2-ethoxyacrylate[ No CAS ]
[ 791-28-6 ]
Yield
Reaction Conditions
Operation in experiment
With N,N,N1,N1-tetramethylguanidine; ammonium chloride; In chloroform;
Preparation d-5 Ethyl (2Z)-3-[6-(benzyloxy)pyridin-3-yl]-2-ethoxyacrylate To a solution of <strong>[635712-99-1]6-(benzyloxy)nicotinaldehyde</strong> (1.0 eq., 33.1 mmol, 7.05 g) and (1,2-diethoxy-2-oxoethyl)(triphenyl)phosphonium chloride (2.0 eq., 66.2 mmol, 28.4 g) in chloroform (165 mL, 0.2 M) was added tetramethylguanidine (3.0 eq., 99.3 mmol, 11.4 g). The flask was capped with a hollow glass stopper and stirred at room temperature overnight. TLC analysis after approximately 18 hours indicated the presence of a small amount of unreacted starting material. The reaction mixture was heated to reflux and TLC reanalyzed after 2 hours. The reaction was quenched with saturated ammonium chloride. The layers were separated and the organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacua. A large amount of triphenylphosphine oxide precipitated. The residue was triturated with ether and filtered. Washed filter cake with ether and concentrated combined filtrates in vacuo to afford a pale yellow solid which was dissolved in a minimal amount of DCM and loaded onto Biotage Sp4 65i and eluted over a gradient of 10-100% hexanes to ethyl acetate. Obtained 12.3 g of a clear, colorless oil (37.6 mmol, quant.). LRMS: 328 (M+H)+. 1H NMR (DMSO-d6, 400 MHz): delta 8.33 (1 H, s) 7.92 (1 H, d, J=8.0 Hz) 7.31-7.43 (5 H, m) 6.76 (1 H, d, J=8.1 Hz) 6.60 (1 H, s) 5.37 (2 H, s) 4.23 (2 H, q, J=7.1 Hz) 3.90-3.99 (2 H, m) 1,34 (6 H, dt, J=15.8, 7.0 Hz).
With sodium hydrogencarbonate; In 1,2-dimethoxyethane; water; at 80℃; for 5.75h;
Example 1, Step d di-tert-butyl (2S,2'S)-2,2'-(4,4'-biphenyldiylbis(]H-imidazole-5,2-diyl))di(1-pyrrolidinecarboxylate) Pd(Ph3P)4 (59.9 mg, 0.0518 mmol) was added to a mixture of bromide 1b (576.1 mg, 1.469 mmol), boronate 1c (621.8 mg, 1.415 mmol), NaHCO3 (400.4 mg, 4.766 mmol) in 1,2-dimethoxyethane (12 mL) and water (4 mL). The reaction mixture was flushed with nitrogen, heated with an oil bath at 80 C. for 5.75 hours, and then the volatile component was removed in vacuo. The residue was partitioned between 20% methanol/CHCl3 (60 mL) and water (30 mL), and the aqueous phase was extracted with 20% methanol/CHCl3 (30 mL). The combined organic phase was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. A silica gel mesh was prepared from the resulting crude material and submitted to flash chromatography (ethyl acetate) to provide dimer id, contaminated with Ph3PO, as an off-white solid (563 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): 6 12.21-12-16/11.95-11.78 (m, 2H), 7.85-7.48/7.32-7.25 (m, 10H), 4.90-4.71 (m, 2H), 3.60-3.32 (m, 4H), 2.30-1.79 (m, 8H), 1.46-1.10 (m, 18H). LC (Cond. 1b): RT=1.77 min; LC/MS: Anal. Calcd. for [M+H]+C36H45BN6O4: 625.35; found 625.48.
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 20℃; for 18h;Product distribution / selectivity;
To a solution of 2- (3-chlorophenyl) ethanol (1.06 g, 6.0 mmol) in CH2CL2 (50 mL) at RT under nitrogen was added CBr4 (1.98 g, 5.8 mmol) and PPh3 (1.57 g, 5.8 mmol). After stirring at RT for 18 h the reaction mixture was concentrated and the residue diluted with ETZO (30 mL) resulting in precipitation of triphenylphosphine oxide. The ethereal solution was decanted, evaporated and purified via flash chromatography (silica, hexane) to provide 2- (3-CHLORO) phenylethyl bromide as a clear oil (57%). 1H NMR (400 MHz, DMSO-d6) 8 7.39-7. 22 (m, 3 H), 7.18-7. 09 (m, 1 H), 3.63-3. 51 (m, 2 H), 3.25-3. 17 (m, 2 H); 13C NMR (100.6 MHz, DMSO-d6) B 141.2, 134.6, 130.7, 129.3, 127.6, 127.3.
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0℃;
Triphenylphosphine (39.2 g, 0.150 mol) and carbon TETRABROMIDE (49.5 g, 0.150 mol) were added sequentially to a solution of 2- (2-hydroxyethyl)-nitrobenzene (25.0 g, 0.150 mol) in methylene chloride (400 mL) at OOC. The reaction was stirred overnight and quenched with saturated sodium bicarbonate solution. The methylene chloride phase was washed with saturated brine and dried over magnesium sulfate. The crude product was treated with ethyl acetate, and the precipitated triphenylphosphine oxide removed by filtration. Further purification by flash chromatography by (silica gel, 0-10percent ethyl acetate in hexane gradient elution) produced the title compound (27.9 g).
4- (3-Fluoro-phenyl)-but-3-enoic acid To a suspension of 3-fluoroaldehyde (13.4 ml, 126 mmol) and (2-carboxy-ethyl)- triphenyl-phosphonium bromide (62.85 g, 151 mmol, 1. 20 equivalents) in anhydrous dichloromethane (150 ml) at 0°C under nitrogen add potassium t-butoxide portion wise (315 mmol, 2.50 equivalents) over two hours and stir at room temperature overnight. Dilute with water, wash with dichloromethane (2x), acidify the aqueous layer with 1N hydrochloric acid to pH 1, dilute with ether, wash with water (2x), dry over anhydrous sodium sulfate, filter, and concentrate to obtain the title compound (24.28 g,-99percent, contains approximately 1.6 g triphenylphophine oxide). NMR (400 MHz, CDC13) : 8 3.26 (d, 2H), 6.32 (m, 1H), 6.48 (d, 1H), 6.95 (t, 1H), 7.08 (d, 1H), 7.14 (d, 1H), 7.27 (m, 1H).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 175℃; for 1h;Microwave irradiation;
Step 1: Synthesis of morpholin-4-yl-[3-(lH-pyrazolo[3,4-b]pyridin-5-yl)-phenyl]-methanone.[0227] A mixture of 5-bromo-l^pyrazolo[3,4-b]pyridine (1.50 g, 7.57 mmol), 3-(morpholin-4-carbonyl)phenylboronic acid (2.136 g, 9.09 mmol) andtetrakis(triphenylphosphine)palladium(0) (435 mL, 0.376 mmol) in dimethoxyethane (8mL) and saturated aqueous solution of sodium bicarbonate (8 mL) was irradiated in aPersonal Chemistry Optimizer at 175 C for 60 min. The crude reaction mixture wasdistributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous phase was then extracted with dichloromethane, and then ethylacetate and the combined organic phases were dried over sodium sulfate, filtered andconcentrated to afford a pale green foam containing 80 % of morpholin-4-yl-[3-(lJfZ-pyrazolo[3,4-b]pyridm-5-yl)-phenyl]-methanone (2.30 g, 80 % yield) and 20 % oftriphenylphosphine oxide. .H-NMR (500 MHz, J6-DMSO) S 13.75 (s, 1H), 8.87 (d, 1H),8.54 (d, 1H), 8.21 (d, 1H), 7.85 (m, 1H), 7.77 (m, 1H), 7.58 (t, 1H), 7.41 (m, 1H).
With 1H-imidazole; iodine; In diethyl ether; acetonitrile; at 0 - 20℃;
A mixture of tert-bntyl 3-hydroxypropylcarbamate (19.36 g, 110.5 mmol), triphenylphosphine (34.76 g, 132.6 mmol), imidazole (10.53 g, 154.7 mmol), diethyl ether EPO <DP n="90"/>(500 mL), and acetonitrile (150 mL) was cooled to approximately 0 C, and iodine (36.45 g, 143.6 mmol) was added in one portion. The reaction mixture was allowed to warm to room temperature slowly and stirred overnight. A precipitate formed, which was removed by filtration and washed with a small amount of diethyl ether. The filtrate was washed sequentially with water (2 x 500 mL), saturated aqueous sodium thiosulfate (2 x 250 mL), water (250 mL), and brine (250 mL); dried over magnesium sulfate; filtered; and concentrated under reduced pressure to provide a mixture of a yellow oil and a white solid. The mixture was diluted with heptane (50 mL) and filtered to remove the solid, which was washed with heptane (50 mL). The filtrate was concentrated under reduced pressure to provide an oil that was diluted with heptane (50 mL) and filtered to remove a solid, which was washed with heptane (50 mL). The filtrate was concentrated under reduced pressure to provide 22.60 g of tert~buty 3-iodopropylcarbamate as a yellow oil containing about 9 mol% triphenylphosphine oxide as determined by 1H NMR.
With diethylazodicarboxylate; In tetrahydrofuran; hexane;
To a stirring, 0 C. solution of 3,5-dimethyl-4-hydroxybenzaldehyde (1.5018 g, 10 mmol), <strong>[146667-84-7]N-Boc-3-piperidineethanol</strong> (2.153 g, 10 mmol), and triphenylphosphene (2.964 g, 11.3 mmol) in 40 mL THF, was added dropwise over 10 min 1.78 mL (11.3 mmol) DEAD the mixture was mixed slowly and allowed to warm to ambient temperature and stirred for 12 hours. The mixture was concentrated in vacuo, and Hexane/DCM was added to precipitate out triphenylphosphene oxide, which was filtered off. The filtrate was concentrated in vacuo, and the residue was flash chromatographed on silica gel, the appropriate fractions combined to give the desired boc-amino ether.
With MgCl2; magnesium chloride; In tetrahydrofuran; water; ethyl acetate; acetonitrile;
16) Removal of triphenylphosphine oxide from 1-bromo-2-(3.4-dimethoxyphenyl)-ethane reaction mixture using MgCl2 (1 eq) A mixture of 2-(3,4-dimethoxyphenyl)ethyl alcohol (3.64 g) and <strong>[1034-39-5]dibromotriphenylphosphorane</strong> (8.44 g) in acetonitrile (30 ml) was stirred at 0-5 C. for 2.5 days. The solvent was removed Th vacuo and the residue was dissolved in ethyl acetate (50 ml) and water (20 ml). The organic layer was separated and dried (MgSO4), and the solvent then removed in vacuo. A sample was analyzed by Gc for triphenylphosphine oxide content. Magnesium chloride (1.9 g) and tetrahydrofuran (15 ml) were added to the residue. The mixture was heated under reflux for 3 hours, left to stand for 16 hours at ambient temperature, cooled to 0 C. for 3 hours, filtered and the filter pad washed with tetrahydrofuran (10 ml). The solvent was removed from the filtrate in vacuo and the residue extracted with ethyl acetate (20 ml). The extract was filtered, washed with water (20 ml), and the solvent then removed in vacuo to yield a residue which was analyzed by Gc for triphenylphosphine oxide content. % Triphenylphosphine oxide content by normalisation by Gc analysis
With MgCl2; magnesium chloride; In tetrahydrofuran; water; ethyl acetate; acetonitrile;
16) Removal of triphenylphosphine oxide from 1-bromo-2-(3.4-dimethoxyphenyl)-ethane reaction mixture using MgCl2(1 eq) A mixture of 2-(3,4-dimethoxyphenyl)ethyl alcohol (3.64 g) and <strong>[1034-39-5]dibromotriphenylphosphorane</strong> (8.44 g) in acetonitrile (30 ml) was stirred at 0-5C for 2.5 days. The solvent was removed Th vacuo and the residue was dissolved in ethyl acetate (50 ml) and water (20 ml). The organic layer was separated and dried (MgSO4), and the solvent then removed in vacuo. A sample was analyzed by Gc for triphenylphosphine oxide content. Magnesium chloride (1.9 g) and tetrahydrofuran (15 ml) were added to the residue. The mixture was heated under reflux for 3 hours, left to stand for 16 hours at ambient temperature, cooled to 0C for 3 hours, filtered and the filter pad washed with tetrahydrofuran (10 ml). The solvent was removed from the filtrate in vacuo and the residue extracted with ethyl acetate (20 ml). The extract was filtered, washed with water (20 ml), and the solvent then removed in vacuo to yield a residue which was analyzed by Gc for triphenylphosphine oxide content.
3-[2-(3.4-dichlorophenyl)-ethenyl]indole-5-carbonitrile[ No CAS ]
[ 17380-18-6 ]
bromo[(3,4-dichlorophenyl)methyl]triphenylphosphorane[ No CAS ]
[ 791-28-6 ]
Yield
Reaction Conditions
Operation in experiment
With MgCl2; In tetrahydrofuran; water; ethyl acetate;
14) Removal of triphenylphosphine oxide from 3-[2-(3.4-dichlorophenyl)-ethenyl]indole-5-carbonitrile reaction mixture using MgCl2 (2.2 eq) n-Butyllithium (2.5M solution in hexanes, 3.6 ml) was added to a stirred solution of (3,4-dichlorobenzyl)triphenylphosphonium bromide (4.4 g) in tetrahydrofuran (20 ml) at 0-5 C. under nitrogen and the mixture then stirred at ambient temperature for 30 minutes. 3-Formylindole-5-carbonitrile (1.0 g) was added in portions over 5 minutes. The resulting mixture was stirred for 25 minutes, diluted with tetrahydrofuran (10 ml) and then heated under reflux for 2.5 hours. water (20 ml) followed by ethyl acetate (25 ml) were added to the cooled mixture and the layers were separated. The ethyl acetate layer was washed with water (2*30 ml) and then brine (30 ml), then dried (MgSO4) and the solvent removed in vacuo to give a residue which was analyzed by NMR for triphenylphosphine oxide content.
With MgCl2; In tetrahydrofuran; water; ethyl acetate;
14) Removal of triphenylphosphine oxide from 3-[2-(3.4-dichlorophenyl)-ethenyl]indole-5-carbonitrile reaction mixture using MgCl2(2.2 eq) n-Butyllithium (2.5M solution in hexanes, 3.6 ml) was added to a stirred solution of (3,4-dichlorobenzyl)triphenylphosphonium bromide (4.4 g) in tetrahydrofuran (20 ml) at 0-5C under nitrogen and the mixture then stirred at ambient temperature for 30 minutes. 3-Formylindole-5-carbonitrile (1.0 g) was added in portions over 5 minutes. The resulting mixture was stirred for 25 minutes, diluted with tetrahydrofuran (10 ml) and then heated under reflux for 2.5 hours. water (20 ml) followed by ethyl acetate (25 ml) were added to the cooled mixture and the layers were separated. The ethyl acetate layer was washed with water (2 x 30 ml) and then brine (30 ml), then dried (MgSO4) and the solvent removed in vacuo to give a residue which was analyzed by NMR for triphenylphosphine oxide content.
EXAMPLE 12 4,6-Dihydroxypyrimidine (0.5 g, 4.46 mmol) was suspended in chlorobenzene (10 ml) and dichlorotriphenylphosphorane (1.44 g, 4.46 mmol; previously prepared by the reaction of triphenylphosphine oxide with phosgene) was added as a solid. The mixture was stirred at 80 C. to 90 C. under a nitrogen atmosphere. Analysis by thin layer chromatography (tlc) of a sample removed after 90 minutes showed some 4,6-dichloropyrimidine formation. However, quite a lot of <strong>[1193-24-4]4,6-dihydroxypyrimidine</strong> remained out of solution. Another quantity of dichlorotriphenylphosphorane (1.44 g, 4.46 mmol) was added and stirring continued for a further hour at 110 C. A cloudy yellow solution was obtained with a solid residue. Analysis by tlc confirmed the formation of 4,6-dichloropyrimidine.
4-[3-[4-(1-imidazolyl)benzyloxy]phenyl]-4-methoxy-3,4,5,6-tetrahydro-2H-pyran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
17%
With triphenylphosphine; In tetrahydrofuran; dichloromethane; acetone;
EXAMPLE 1 4-[3-[4-(1-Imidazolyl)benzyloxy]phenyl]-4-methoxy-3,4,5,6-tetrahydro-2H-pyran To a stirred solution of 4-(1-imidazolyl)benzyl alcohol (Eur. J. Med. Chem., 1992, 27, 219) (0.87 g, 5.0 mmol), 4-(3-hydroxyphenyl)-4-methoxy-3,4,5,6-tetrahydro-2H-pyran (J. Med. Chem., 1992, 35, 2600) (1.03 g, 4.9 mmol) and triphenylphosphine (1.55 g, 5.9 mmol) in THF (30 ml) cooled to 0 C. was added dropwise a solution of diethyl azodicarboxylate (DEAD) (1.03 g, 12.0 mmol) in THF (10 ml) over 20 min under a nitrogen atmosphere. After completion of addition, the mixture was stirred at 0 C. for 30 min and allowed to warm to room temperature, and then volatiles were removed under reduced pressure. Chromatographic purification of the residue (SiO2, 230 g; gradient elution, 15% to 30% acetone in dichloromethane) provided 0.27 g of the title compound as a gum, which solidified on standing at room temperature. Fractions contaminated with triphenylphosphine oxide were combined, concentrated to dryness, solidified by triturating with diisopropyl ether and recrystallized from diisopropyl ether / ethyl acetate to provide 0.16 g of the title compound. Combined solids were further purified by recrystallization from diisopropyl ether / ethyl acetate afforded the title compound as tiny colorless needles (0.30 g, 17%). m.p.: 129-130.5 C. IR (KBr) cm-1: 2960, 2875, 1607, 1579, 1524, 1480, 1306, 1281, 1251, 1073, 1061, 1026. 1 H NMR (CDCl3) delta: 7.78 (t, 1H, J=1 Hz), 7.56 (d, 2H, J=8 Hz), 7.43 (d, 2H, J=8 Hz), 7.32 (t, 1H, J=8 Hz), 7.28 (dd, 1H, J=1, 8 Hz), 7.22 (t, 1H, J=1 Hz), 7.08-6.98 (m, 2H), 6.94-6.88 (in, 1H), 5.12 (s, 2H), 3.92-3.81 (m, 4H), 2.98 (s, 3H), 2.10-1.92 (m, 4H).
With trifluoromethylsulfonic anhydride; In dichloromethane;
(E) Preparation of 2-chloro-5-methoxynicotinonitrile Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2 Cl2 (50 mL) and the mixture cooled to 0-4 C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2 Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2 CO3 solution and extracted with CHCl3 (2*). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86%) of 2-chloro-5-methoxynicotinonitrile 1 H NMR (CDCl3) delta3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm- 1.
6.2 g (86%)
With trifluoromethylsulfonic anhydride; In dichloromethane;
(E) Preparation of 2-chloro-5-methoxynicotinonitrile Into a flame dried flask under N2 was placed triphenylphosphine oxide (12.0 g, 0.04 mol) and CH2 Cl2 (50 mL) and the mixture cooled to 0-4 C. A solution of triflic anhydride (6.75 ml, 0.04 mol) in CH2 Cl2 (80 mL) was added dropwise. After the addition, the solution was stirred for 15 min. and 2-chloro-5-methoxynicotinamide (8.0 g, 0.04 mol) was added portionwise over 15 minutes. The mixture was allowed to warm to room temperature with stirring overnight, poured into saturated Na2 CO3 solution and extracted with CHCl3 (2X). After concentration, the residue was chromatographed on silica gel and the product eluted with CHCl3 to yield 6.2 g (86%) of 2-chloro-5-methoxynicotinonitrile 1 H NMR (CDCl3) delta 3.9 (3H, s), 7.5 (1H, d, J=3) and 8.3 (1H, d, J=3); (nujol) 2250 cm-1.
1,068,709, by reaction with triphenylphosphine and sulfuric acid. Melting point 150 - 155 C. 8 g of this triphenylphosphonium bisulfate are dissolved in 70 ml of water; 30 ml of 30 percent strength by weight hydrogen peroxide are added and 10 percent strength by weight aqueous sodium carbonate solution is then added dropwise whilst stirring. The temperature rises to +30 C. The mixture is then stirred for three hours at room temperature. The precipitated triphenylphosphine oxide and the lycopene are filtered off and washed with warm water. The residue is suspended in ethanol, the suspension is stirred at room temperature and the product is filtered off.
47
[ 558-13-4 ]
[ 13246-46-3 ]
[ 791-28-6 ]
[ 170281-92-2 ]
Yield
Reaction Conditions
Operation in experiment
67%
With triphenylphosphine; In dichloromethane; pentane;
Reference Example 3 A mixture of triphenylphosphine (15.7 g) and carbon tetrabromide (9.93 g) in dry dichloromethane (100 mL) is cooled to 0 C. and stirred for 30 minutes. A solution of <strong>[13246-46-3]2,4-dibenzyloxybenzaldehyde</strong> (4.76 g) in dichloromethane (30 mL) is added and the solution stirred at 0 C. for 2 hours. The solution is treated with pentane to precipitate triphenylphosphine oxide. The filtrate is evaporated to give 1-(2,4-dibenzyloxyphenyl)-2,2-dibromoethylene as a yellow oil (4.85 g, 67%).
With hydrogen; In tetrahydrofuran; at 120 - 150℃; under 187519.0 Torr;
1. Hydrogenation of Triphenylphosphine Oxide; A mixture of triphenylphosphine oxide (707 g, 2.54 mol) and a suspension of ruthenium(IV) oxide hydrate (supported on aluminum oxide) (140 g, comprises 3 g of ruthenium) in tetrahydrofuran (2 l) was hydrogenated at from 120 to 150 C. and a hydrogen pressure of 250 bar with stirring. After cooling to room temperature, the catalyst was filtered off and the filtrate was freed of the solvent under reduced pressure. Distillation of the residue at from 200 to 210 C. (1 mbar) afforded 722 g (96% of theory) of tricyclohexylphosphine oxide in the form of a white solid.
(3R)-(tert-butyl-dimethyl-silanyloxy)-5-oxo-6-(triphenylphosphoranylidene)-hexanoate[ No CAS ]
[ 147118-37-4 ]
3-(tert-butyl-dimethyl-silanyloxy)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(methylsulfonyl-methyl-amino)pyrimidin-5-yl]-5-oxo-hept-6-enoic acid methyl ester[ No CAS ]
[ 791-28-6 ]
Yield
Reaction Conditions
Operation in experiment
In acetonitrile; for 15h;Reflux;Product distribution / selectivity;
N-[4-(4-Fluoro-phenyl)-5-formyl-6-isopropyl-pyrimidin-2-yl]-N-methyl- methane- sulfonamide (100 g) and methyl (3R)-(tert-butyl-dimethyl-silanyloxy)-5-oxo-6- (triphenylphosphoranylidene)-hexanoate (228 g) was taken in acetonitrile (200 ml) and refluxed for 15 hours. After completion of reaction (monitored by TLC), solvent was distilled off completely. Isopropyl ether (400 ml) was added to resulting residue to crystallize by- product triphenylphosphine oxide (TPPO). The reaction mixture was filtered to remove triphenylphosphine oxide (TPPO) and insoluble particulate. Resulting filtrate was concentrated under vacuum to get 225 g of title compound.A portion of resulting product was purified by column chromatography to give title compound having purity 96.6 %; triphenylphosphine oxide 0.12% by HPLC.
With palladium diacetate; potassium carbonate; tricyclohexylphosphine; In N,N-dimethyl-formamide; at 180℃; for 1h;Inert atmosphere; Microwave irradiation;
General procedure: 5-Bromopyrimidine (1) (79mg, 0.5mmol), the corresponding 2-(het)aryl substituted thiophene (2a, 2b or 2c) (1.0mmol), Pd(OAc)2 (11mg, 10mol%), PCy3 (28mg, 0.1mmol), and K2CO3 (207mg, 1.5mmol) were dissolved in DMF (5mL). The resulting reaction mixture was deaerated by bubbling argon and irradiated in a microwave apparatus at 180C (250W) for 10min. After that the solvent was distilled off under reduced pressure, and the residue was purified by flash column chromatography (hexane/ethyl acetate, 1:2) to afford the desired product (3a, 3b or 3c). Yields ofreaction products are based on the molar amount of 5-bromopyrimidine used. The regioisomeric products 4a, 4b, and 4c were not isolated.
With potassium carbonate; In [(2)H6]acetone; at 60℃; for 3h;Inert atmosphere;
To a J-Young NMR tube were added triphenylphosphine oxide (1,19.5 mg, 0.070 mmol), [IrCp*Cl2]2 (27.9 mg, 0.035 mmol), AgNTf2(54.3 mg, 0.14 mmol), and acetone-d6 under argon atmosphere, andthe reaction mixture was stirred at room temperature for 10 min. Tothis solution was added K2CO3 (19.4 mg, 0.14 mmol) and the mix-ture was allowed to heat at 60 C for 3 h, forming complex 3 in 70%NMR yield based on 31P NMR analysis. Subsequent addition of TsN3(13.8 mg, 0.070 mmol) into the above solution containing complex3 afforded a complex 4 with >95% conversion at room temperaturein 4 h. Complexes 3 and 4 were analyzed by 31P NMR spectroscopicand ESI-MS in each step of these transformations.
General procedure: Method A. In a flame-dried Schlenk tube (50 mL) equipped with magnetic stirrer and an inert gas inlet substrate (0.5 mmol) was dissolved in 10 mL THF. The mixture was cooled to -78 C and commercial organolithium or Grignard reagent (1.0 mmol) was added at once. The mixture was allowed to warm to room temperature over 24 h. The reaction was quenched by addition of saturated NH4Cl solution (10 mL) and extracted with DCM (3×20 mL). The combined organic phases were dried over MgSO4, filtered, and evaporated under the reduced pressure. The residue was purified by flash column chromatography. Method B. In a flame-dried Schlenk tube (50 mL) equipped with magnetic stirrer and an inert gas inlet aryl or alkyl halide (1.0 mmol) was dissolved in 10 mL Et2O. The mixture was cooled to -78 C and organolithium (1.0 mmol) was added gradually. After the mixture was stirred for 2 h, the reaction was allowed to warm to room temperature and the substrate (0.5 mmol) was added. The mixture was stirred for 24 h. The reaction was quenched by addition of saturated NH4Cl solution (10 mL) and extracted with DCM (3×20 mL). The combined organic phases were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by flash column chromatography.
With sodium hexamethyldisilazane; 3,5-dimethyl-4H-pyrazole; trifluoroacetic anhydride; In tetrahydrofuran; at -60 - 20℃; for 2.5h;Inert atmosphere;
Put 15 g of triphenylphosphine oxide,0.5 g of 3,5-dimethyl-4H-pyrazole,Trifluoroacetic anhydride 0.55g,Dissolve in 100 ml of tetrahydrofuran for use.25 g of the compound III obtained above,Add 200 ml of anhydrous tetrahydrofuran,Nitrogen protection,Cool to -60 ~ -50 C,Add 2mol/L NaHMDS 30ml,After the drop,The above prepared triphenylphosphine oxide solution is added dropwise,Reaction for 2 hours,Slowly warm up to 20 C,Keep it for 0.5 hours.Pour the reaction solution into 2% ammonium chloride ice water.Stir for 10min,The aqueous phase was extracted with 200 ml of toluene.50 ml of toluene is extracted once more.Wash 100ml of water twice,Filtered through diatomaceous earth,Concentrated under reduced pressure,Add 50 ml of cyclohexane,Heated to 60 C,Filtered through diatomaceous earth,Cool to 10 C,Keep warm for more than 5 hours,filter,Vacuum drying to obtain 21.5 g of methyl (3R)-tert-butyldimethoxysiloxy-5-oxo-6-triphenylphosphanylidenehexanoate (I) with a purity of 99.7%.The yield was 77.6%.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
