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CAS No. : | 6163-58-2 |
Formula : | C21H21P |
M.W : | 304.37 |
SMILES Code : | C1=CC=CC(=C1P(C2=C(C=CC=C2)C)C3=C(C=CC=C3)C)C |
MDL No. : | MFCD00008514 |
InChI Key : | COIOYMYWGDAQPM-UHFFFAOYSA-N |
Pubchem ID : | 80271 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;palladium diacetate; In tetrahydrofuran; water; | To a stirred solution of tert-butyl (1R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate (1.0 g, 2.9 mmol) and <strong>[146014-66-6]methyl 2-fluoro-6-iodobenzoate</strong> (1.2 g, 4.32 mmol) in 25 mL of a 5:1 THF:water mixture was added potassium carbonate (1.2 g, 8.64 mmol), tri-o-tolylphosphine (350 mg, 1.15 mmol) and lastly palladium acetate (65 mg, 0.29 mmol). The reaction vessel was then sealed and placed into a 90 C. oil bath for overnight stirring and heating. After about 18 hours the reaction mixture was cooled to ambient temperature and then diluted with EtOAc. The organics were washed with brine (*4), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give an oil. This oil was subject to silica gel chromatography eluding with 10-60% EtOAc in hexanes to provide methyl 4'-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl }-3-fluoro-1,1'-biphenyl-2-carboxylate (205 mg), found to be pure by LC/MS and proton NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;palladium diacetate; In tetrahydrofuran; water; ethyl acetate; | A mixture of <strong>[685892-23-3]methyl 2-bromo-6-chlorobenzoate</strong> (2.25 g, 9.03 mmol), tert-butyl (1R)-1-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-ethylcarbonate (see Example 11, 3.00 g, 8.21 mmol), potassium carbonate (2.84 g, 20.5 mmol), tri-o-tolylphosphine (0.10 g, 0.33 mmol), and palladium acetate (0.018 g, 0.08 mmol) in 40 mL of THF and 4 mL of water was heated in a sealed flask at 100 C. for 4 h. The mixture was then cooled and concentrated in vacuo. The resulting residue was dissolved in ethyl acetate, washed with water and brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was subjected to silica gel chromatography eluted with 0-10% ethyl acetate and hexane to provide methyl 4'-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-3-chloro-3'-fluoro-1,1'-biphenyl-2-carboxylate that gave proton NMR spectra consistent with theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With triethylamine;palladium diacetate; | 3-(2-Methylindol-5-yl)acrylic Acid Methyl Ester A mixture of <strong>[1075-34-9]5-bromo-2-methylindole</strong> (2.10 g, 10.0 mmol), methyl acrylate (1.08 g, 12.5 mmol), palladium acetate (23.2 mg, 0.1 mmol), tri(o-tolyl)phosphine (61.3 g, 0.2 mmol) and triethylamine (3.62 g, 35.8 mmol) was heated under argon in a heavy-walled Pyrex tube at 100° C. for 3 h. The cooled reaction mixture was diluted with DCM (60 mL) and distilled water (30 mL). The organic layer was washed with distilled water (3*25 mL). The aqueous is layer was extracted with DCM (25 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give a pale yellow solid. Purification by recrystallization with EtOAc gave a pale yellow powder (1.57 g; 73percent): mp 172-173° C.; Rf0.35 (C); Rf0.61 (E); numax (KBr): 3295, 1698, 1305, 1282, 1165, 975 cm-1; m/z (EI): 215.1, 184.1, 156.1, 77.2; deltaH (CDCl3, 400 MHz): 2.45 (3 H, s), 3.82 (3 H, s), 6.25 (1 H, s), 6.42 (1 H, d, J=16.0), 7.27 (1 H, d, J=8.0), 7.35 (1 H, d, J=8.0), 7.69 (1 H, s), 7.85 (1 H, d, J=16.0), 8.15 (1 H, bs); deltaC (CDCl3, 101 MHz): 14.0, 51.8, 101.5, 111.0, 114.5, 121.1, 121.4, 126.5, 129.7, 136.7, 137.7, 147.4, 168.6; m/z calculated for C13H13NO2: 215.0946 (M+), found 215.0945 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; dichloromethane; | To a suspension of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (2.23 g), 1-(tert-butoxycarbonyl)-4-(piperidin-4-ylcarbonyl)piperazine (1.49 g) and sodium t-butoxide (1.06 g) in 1,4-dioxan (20 ml) was added tris(dibenzylidene acetone)dipalladium(0) (0.09 g) and tri-o-tolylphosphine (0.12 g) and the mixture heated at reflux for 3 hours. The mixture was diluted with diethyl ether and washed with saturated aqueous sodium chloride solution, dried (Na2SO4) and evaporated. The residue was purified by chromatography on alumina (N32-63) eluding with 0.4percent methanol in dichloromethane to give as a solid, 1-(tert-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperidin-4-ylcarbonyl]piperazine (0.70 g). 1H-NMR (CDCl3): 1.45 (s, 9H), 1.80 (m, 2H), 2.00 (m, 2H), 2.65 (m, 1H), 2.90 (m, 2H), 3.40 (m, 8H), 3.80 (m, 2H), 6.70 (dd, 1H), 8.10 (d, 1H) and 8.20 (d, 1H); m/z 393 (M+1). | |
In 1,4-dioxane; dichloromethane; | To a suspension of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (2.23 g), 1-(tert-butoxycarbonyl)-4-(piperidin-4-ylcarbonyl) piperazine (1.49 g) and sodium t-butoxide (1.06 g) in 1,4-dioxan (20 ml) was added tris(dibenzylidene acetone)dipalladium(0) (0.09 g) and tri-o-tolylphosphine (0.12 g) and the mixture heated at reflux for 3 hours. The mixture was diluted with diethyl ether and washed with saturated aqueous sodium chloride solution. dried (Na2SO4) and evaporated. The residue was purified by chromatography on alumina (N32-63) eluding with 0.4percent methanol in dichloromethane to give as a solid, 1-(tert-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperidin-4-ylcarbonyl]piperazine (0.70 g). 1H-NMR (CDCl3): 1.45 (s, 9H), 1.80 (m, 2H), 2.00 (m, 2H), 2.65 (m, 1H), 2.90 (m, 2H), 3.40 (m, 8H), 3.80 (m, 2H), 6.70 (dd, 1H), 8.10 (d, 1H) and 8.20 (d, 1H); m/z 393 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; methanol; dichloromethane; | Tris(dibenzylideneacetone)dipalladium(0) (0.184 g) and tri-o-tolylphosphine (0.244 g) were added to a suspension of <strong>[22282-75-3]3-fluoro-4-iodopyridine</strong> (4.46 g), 1-[1-(t-butoxycarbonyl)piperazin-4-ylcarbonyl]piperazine (3.0 g) and sodium t-butoxide (2.12 g) in dry 1,4-dioxane (40 ml) under an atmosphere of argon. The mixture was heated at 100° C. for 18 hours. The mixture was cooled, diluted with diethyl ether (200 ml) and washed with saturated brine (40 ml). The aqueous layer was back-extracted with diethyl ether (2*100 ml). The ether layers were all combined, washed with saturated brine (2*100 ml), dried (Na2SO4) and evaporated. The residual oil was purified by chromatography on alumina (N32-63) using 0.1-0.4percent methanol in dichloromethane as eluent to give 1-(t-butoxycarbonyl)-4-[1-(3-fluoro-4-pyridyl)piperazin-4-ylcarbonyl]piperazine (1.7 g) as an orange solid: NMR (CDCl3): 1.47 (s, 9H), 3.25 (m, 8H), 3.45 (m, 8H), 6.75 (dd, 1H), 8.20 (dd, 2H); m/z 394 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate; triethylamine; lithium chloride; In N,N-dimethyl-formamide; | (x) 4-{2-[3-(1-tert-Butoxycarbonylmethyl-piperidin-4-yl)-1-(4-fluoro-benzyl)-1H-indazol-6-yl]-(E)-vinyl}-piperidine-1-carboxylic acid tert-butyl ester A stirred mixture of {4-[6-bromo-1-(4-fluoro-benzyl)-1H-indazol-3-yl]-piperidin-1-yl}-acetic acid tert-butyl ester (286 mg, 0.57 mmol), <strong>[180307-56-6]4-vinyl-piperidine-1-carboxylic acid tert-butyl ester</strong> (120 mg, 0.57 mmol), lithium chloride (24 mg, 0.57 mmol), triethylamine (0.24 ml, 1.71 mmol), palladium (II) acetate (8 mg 0.03 mmol), tri-o-tolylphosphine (35 mg, 0.11 mmol), and DMF (5 ml) was heated at 105 (oil-bath temperature) under nitrogen for 18 h. When cool, the mixture was evaporated in vacuo, treated with aqueous saturated sodium bicarbonate (20 ml), and extracted with ethyl acetate (2*20 ml). The combined, dried (Na2 SO4) organic extracts were evaporated, and the residue purified by flash chromatography over silica gel (Merck 9385). Elution with ethyl acetate --cyclohexane (1:2) afforded impure fractions and pure fractions (I). The impure fractions were purified by flash chromatography over silica gel (Merck-9385) eluding with ethyl acetate--cyclohexane (gradient 1:4 to 1:2) to give pure fractions (II). The pure fractions (I) and (II) were combined to give the title compound as a pale yellow oil (195 mg). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;palladium(II) chloride; In dichloromethane; water; | To a mixture of 27 g of 4-(t-butoxycarbonylamino)-bromobenzene, 0.18 g of palladium chloride, 1.25 g of tri-O-tolylphosphine and 50 ml of triethylamine is added 9.5 ml of acrylic acid followed by 25 ml of triethylamine. The reaction mixture is heated under reflux for 3 hours. Methylene chloride (250 ml) is added, the reaction mixture is filtered and evaporated to dryness. The residue is suspended in water, the suspension is washed with toluene, concentrated HCl is added while cooling to pH5. The resulting 4-(t-butoxycarbonylamino)-cinnamic acid is collected, washed with water and dried; m.p. 175-177. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.1% | With sodium hydrogencarbonate;palladium diacetate; In 1-methyl-pyrrolidin-2-one; | Preparation 10 5-(2-methyl-3-oxobutyl)-thiophene-2-sulfonamide 5-bromothiophene-2-sulfonamide (5.2 g, 21.5 mmol) and 3-methyl-3-buten-2-ol (2.8 g, 32.2 mmol) were dissolved in N-methylpyrrolidinone (40 mL) and treated with catalytic palladium diacetate (96 mg, 0.43 mmol), tris-(o-tolyl)-phosphine (262 mg, 0.86 mmol), and NaHCO3(2.2 g, 25.8 mmol). The mixture was stirred at 160C for 48 hours. TLC indicated the reaction was ca. 50% completed at that time. The solution was cooled to ambient temperature and partitioned between H2O/ethyl acetate, dried (MgSO4) and concentrated in vacuoto a dark brown oil. The residue was applied to a silica chromatography column and eluted with 2:3 hexane/ethyl acetate to yield 220 mg of a pale brown oil (4.1%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;palladium diacetate; In toluene; | Referential Example 14 19 mg of palladium acetate (II) was added to 5 mL of toluene solution containing 0.50 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 50 mg of tri(o-tolyl)phosphine, 0.44 mL of allylbenzene and 0.46 mL of triethylamine, and the resulting mixture was heated to reflux under nitrogen atmosphere for 2 hours. After the reaction mixture was cooled to room temperature, 20 mg of palladium acetate (II) was added and the resulting mixture was heated to reflux for 7 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [eluent; hexane:ethyl acetate = 30:1] to obtain 0.31 g of tert-butyl 2-nitro-4-(3-phenyl-1-propenyl)benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine;palladium diacetate; In toluene; | Referential Example 15 19 mg of palladium acetate (II) was added to 5 mL of toluene solution containing 0.50 g of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong>, 50 mg of tri(o-tolyl)phosphine, 0.50 mL of 4-phenyl-1-butene and 0.46 mL of triethylamine, and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours and 30 minutes. After the reaction mixture was cooled to room temperature, 20 mg of palladium acetate (II) was added and the resulting mixture was heated to reflux for 5 hours and 30 minutes. After cooled to room temperature, the reaction mixture was purified with silica gel column chromatography [eluent; hexane:ethyl acetate = 30:1] to obtain 0.35 g of tert-butyl 2-nitro-4-(4-phenyl-1-butenyl)benzoate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
palladium diacetate; In methanol; ethanol; hexane; water; acetone; toluene; | Synthesis Method of 3,6-di(dibenzofuran-4-yl)-9-phenyl-9H-carbazole (abbreviated as DBF2PC-II)To a 200-mL three-neck flask were added 2.0 g (5.0 mmol) of <strong>[57103-20-5]3,6-dibromo-9-phenyl-9H-carbazole</strong>, 3.2 g (11 mmol) of dibenzofuran-4-boronic acid, 10 mg (0.1 mmol) of palladium(II) acetate, 30 mg (0.1 mmol) of tris(o-tolyl)phosphine, 50 mL of toluene, 5 mL of ethanol, and 7.5 mL of a 2 mol/L aqueous potassium carbonate solution.This mixture was degassed while being stirred under reduced pressure, and then heated and stirred at 90° C. for 6.5 hours under a nitrogen stream to be reacted.After the reaction, 250 mL of toluene was added to this reaction mixture and the mixture was heated.The mixture was filtered through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), alumina, and Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135) in this order to give a filtrate.The resulting filtrate was purified by silica gel column chromatography (a developing solvent in which the toluene/hexane ratio was 1:3).The obtained fraction was concentrated, acetone, methanol, and water were added thereto, and the mixture was irradiated with ultrasonic waves.Then, acetone and methanol were added to the obtained precipitate and the mixture was irradiated with ultrasonic waves, filtrated, washed, and dried.Thereby, 2.8 g of a target substance, white powder, was obtained in 69percent yield.A reaction scheme of the above synthesis method is illustrated in the following (E-1).The Rf values of the white powder obtained through the reaction and <strong>[57103-20-5]3,6-dibromo-9-phenyl-9H-carbazole</strong> were respectively 0.32 and 0.55, which were found by silica gel thin layer chromatography (TLC) (a developing solvent in which the ethyl acetate/hexane ratio was 1:10).The white powder obtained by the step 1 was subjected to nuclear magnetic resonance (NMR) spectroscopy.The measurement data are shown below.show the 1H NMR charts.Note that is an enlarged chart of .By the measurement results, it was confirmed that the white powder obtained by the step 1 was DBF2PC-II, which is represented by the structural formula (208).1H NMR (CDCl3, 300 M Hz): delta (ppm)=7.37 (dt, J=7.8 Hz, J=1.2 Hz, 2H), 7.44-7.56 (m, 5H), 7.60-7.69 (m, 8H), 7.75 (dd, J=7.2 Hz, J=1.5 Hz, 2H), 7.95 (dd, J=7.8 Hz, J=1.5 Hz, 2H), 8.00-8.04 (m, 4H), 8.75 (d, J=1.5 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | palladium diacetate; In ethanol; hexane; acetone; toluene; | Step 1:Synthesis of 3,6-di-(dibenzothiophen-4-yl)-9-phenyl-9H-carbazole (abbreviated as DBT2PC-II)To a 200-mL three-neck flask were added 2.0 g (5.0 mmol) of <strong>[57103-20-5]3,6-dibromo-9-phenyl-9H-carbazole</strong>, 3.2 g (11 mmol) of dibenzothiophene-4-boronic acid, 10 mg (0.1 mmol) of palladium(II) acetate, 30 mg (0.1 mmol) of tri(ortho-tolyl)phosphine, 50 mL of toluene, 5 mL of ethanol, and 7.5 mL of a 2 mol/L aqueous potassium carbonate solution.This mixture was degassed while being stirred under reduced pressure, and then heated and stirred at 90° C. for 6 hours in a nitrogen atmosphere to be reacted.After the reaction, this reaction mixture solution was cooled to room temperature, and then filtered to give a residue while being washed with water, ethanol, toluene, and hexane in this order.The residue was purified by silica gel column chromatography (a developing solvent in which the toluene/hexane ratio was 1:3).The fraction thus obtained was concentrated, acetone and ethanol were added thereto, and the mixture was irradiated with ultrasonic waves.Then, recrystallization gave 1.4 g of a white powder in 47percent yield.The synthesis scheme of Step 1 is shown in (A-1).The obtained white powder was subjected to nuclear magnetic resonance (NMR) spectroscopy.The measurement data are shown below.1H NMR (CDCl3, 300 MHz): delta=7.44-7.70 (m, 15H), 7.82-7.86 (m, 4H), 8.15-8.22 (m, 4H), 8.57 (d, J=1.5 Hz, 2H) |
Tags: Tri(2-methylphenyl)phosphine | Benzene Compounds | Aryls | Phosphoruses | Mono-phosphine Ligands | Organic Building Blocks | Achiral Phosphine Ligands | 6163-58-2
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H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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