Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 25574-11-2 | MDL No. : | MFCD09028724 |
Formula : | C9H11BrO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | WODKXGCVVOOEIJ-UHFFFAOYSA-N |
M.W : | 215.09 | Pubchem ID : | 10560614 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 49.88 |
TPSA : | 20.23 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.98 cm/s |
Log Po/w (iLOGP) : | 2.36 |
Log Po/w (XLOGP3) : | 2.3 |
Log Po/w (WLOGP) : | 2.37 |
Log Po/w (MLOGP) : | 2.91 |
Log Po/w (SILICOS-IT) : | 3.01 |
Consensus Log Po/w : | 2.59 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.83 |
Solubility : | 0.319 mg/ml ; 0.00149 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.36 |
Solubility : | 0.933 mg/ml ; 0.00434 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -3.9 |
Solubility : | 0.0273 mg/ml ; 0.000127 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.17 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
66% | With carbon tetrabromide; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 15.25 h; | Example 138. l-Bromo-4-(3-bromo-propyD-benzene (79); [0322] To a solution of compound 78 described in Example 137 (4.0 g, 19 mmol) inTHF (30 mL) at 0 °C under the argon atmosphere was added PPh3 (6.3 g, 24 mmol) followed by CBr4 (8.0 g, 24 mmol). The mixture was stirred at the same temperature for 15 min and then stirred at room temperature for additional 15 h. Most of the solvent was removed and the residue purified by flash chromatography on silica gel (hexane) to afford the title compound (3.5 g, 66percent) as a colorless oil.[0323] 1H NMR (500 MHz, DMSO-d6): δ 2.03-2.12 (m, 2H), 2.68 (t, J= 7.5 Hz, 2H), 3.49 (t, J= 6.5 Hz, 2H), 7.19 (d, J= 8.3 Hz, 2H), 7.47 (d, J= 8.3 Hz, 2H). |
66% | With carbon tetrabromide; triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 15.25 h; | EXAMPLE 100. Synthesis of l-Broιtio-4-(3-Bromo-Propyl)-Benzene (Intermediate50150[02981 To a solution of intermediate 49 (Example 99) (4.0 g, 19 mmol) in THF (30 mL)O at 0 C under the argon atmosphere was added PPh3 (6.3 g, 24 mmol) followed by CBr4 (8.0 g, 24 mmol). The mixture was stirred at the same temperature for 15 min and then stirred at room temperature for additional 15 h. Most of the solvent was removed and the residue purified by flash chromatography on silica gel (hexane) to afford the title compound (3.5 g, 66percent) as a colorless oil.[0299] 1H NMR (500 MHz, DMSOd6): δ 2.03-2.12 (m, 2H), 2.68 (t, J= 7.5 Hz, 2H), 3.49 (t, J= 6.5 Hz, 2H), 7.19 (d, J= 8.3 Hz, 2H), 7.47 (d, J= 8.3 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With Dess-Martin periodane In dichloromethane at 20℃; for 2 h; | Example A.4: Synthesis of 3-(4-bromophenyl)propanal (10*) Alcohol 4* (4.71g, 21.8mmol) was dissolved in DCM, treated with Dess-Martin periodinane (9.71g, 20.9mmol) and stirred at rt for 2h. The mixture was quenchedwith 2M NaOH, the phases were separated the aqueous layer extracted with DCM. The combined organic phases were dried on Mg504, filtered and evaporated in vacuo. The crude was purified by flash chromatography on silica gel using a gradient of DCM in cHex to yield the desired product 10* (4.46g, 96percent) as a colourless liquid.1H NMR (400MHz, CDCI3) 6 9.81 (5, 1H), 7.41 (d, 2H), 7.07 (d, 2H), 2.91 (t, 2H),2.79-2.74 (m, 2H).MS (ES) C9H9BrO requires: 211/213, (Mi-H) not found, 100percent. |
86% | Stage #1: With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78℃; for 0.5 h; Stage #2: With triethylamine In dichloromethane at -78 - 20℃; for 3 h; |
Oxalyl chloride (0.599 mL, 6.973 mmol) was dissolved in DCM (15 mL), and DMSO (0.99 mL, 13.94 mmol)dissolved in DCM (10 mL) was slowly added thereto at -78°C. The mixture was stirred for 15 minutes, and 3-(4-bromophenyl)propan-1-ol (1.0 g, 4.64 mmol) dissolved in DCM (10 mL) was slowly added thereto at -78°C. The mixture was stirredfor 30 minutes, and TEA (1.96 mL) was slowly added thereto at -78°C. The temperature was slowly increased to roomtemperature, and the reaction solution was stirred for 3 hours. After termination of the reaction, the reaction solutionwas diluted with water and extracted with DCM. The organic layer was dried with anhydrous magnesiumsulfate andpurified by column chromatography (eluent, EtOAc/Hex = 1/5) to obtain the title compound (0.859 g, 86percent).NMR: 1H-NMR (CDCl3) δ 9.81(1H, s), 7.40 (2H, d), 7.07(2H, d), 2.91(2H, m), 2.77(2H, t) |
76.9% | With pyridinium chlorochromate In dichloromethane at 0 - 20℃; for 4 h; | 3-(4-Bromophenyl) propan-1-ol (4 g, 18.5 mmol, 1.0 equiv) was dissolved into dichloromethane (60 mL) and cooled to 0°C. PCC (5.21 g, 24.1 mmol, 1.5 equiv) was added in portions and the reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite bed and the filtrate was concentrated to afford a crude residue. The crude residue was purified by silica gel column chromatography (10-20 percent diethyl ether/n-pentane) to afford the desired product 5.21a (3.05 g, 76.9 percent yield). 1H NMR (400 MHz, CDCI3) 69.83 (s, 1H), 7.43 (d, J = 8.3 Hz, 2H), 7.10 (d, J 8.2 Hz, 2H), 2.94 (t, J 7.3 Hz, 2H), 2.79 (t, J 7.4 Hz, 2H). |
58.5% | With sodium hydrogencarbonate; Dess-Martin periodane In dichloromethane at 0 - 20℃; | To a 0° C. mixture of 26A (7 g, 32.5 mmol) and NaHCO3 (3.28 g, 39.1 mmol) in DCM (200 mL) was added Dess-Martin periodinane (16.56 g, 39.1 mmol) and the reaction was allowed to slowly warm to rt overnight. The reaction was diluted with sat. aq. NaHCO3 (150 mL) and extracted with DCM (50 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was chromatographed (SiO2; 80 g; A=Hex, B=EtOAc; 20 min gradient from 0percent B to 40percent B; flow rate=60 mL/min) to afford the title compound (4.06 g, 19.1 mmol, 58.5percent yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) δ 9.82 (t, J=1.2 Hz, 1H), 7.48-7.37 (m, 2H), 7.19-6.97 (m, 2H), 3.02-2.88 (m, 2H), 2.83-2.70 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With 1-methyl-pyrrolidin-2-one In water | 33B 3-(4-Cyanophenyl)propan-1-ol A mixture of 3-(4-bromophenyl)propan-1-ol (2.0 g, 9.3 mmol), copper (I) cyanide (1.49 g, 16.7 mmol) and N-methylpyrrolidinone (13 ml) was stirred at 200°C for 2.5 hours. After that the reaction mixture was cooled at room temperature, poured onto a solution of diethylamine (30 g) and water (80 ml) and extracted with ethyl acetate (3x40 ml). The combined organic phases were dried and volatiles were removed, to obtain an oil from which N-methylpyrrolidinone was removed by distillation under high vacuum (0.5 torr, 85°C), thereby obtaining 0.78 g of the title compound (52percent yield). 1H N.M.R. (300 MHz, CDCL3) δ ppm: 1.85 (m, 2H); 2.42 (s broad, 1H); 2.76 (t, 2H); 3.64 (t, 2H); 7.29 (d, 2H); 7.53 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.1% | With lithium aluminium tetrahydride In diethyl ether for 48h; | |
With lithium aluminium tetrahydride In tetrahydrofuran for 1h; Heating; | ||
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Reflux; |
With D-Glucose; Escherichia coli endogenous alcohol dehydrogenase; Segniliparus rugosus carboxylic acid reductase; dimethyl sulfoxide; magnesium chloride In aq. phosphate buffer at 30℃; for 18h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With carbon tetrabromide; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 15.25h; | Example 138. l-Bromo-4-(3-bromo-propyD-benzene (79); [0322] To a solution of compound 78 described in Example 137 (4.0 g, 19 mmol) inTHF (30 mL) at 0 C under the argon atmosphere was added PPh3 (6.3 g, 24 mmol) followed by CBr4 (8.0 g, 24 mmol). The mixture was stirred at the same temperature for 15 min and then stirred at room temperature for additional 15 h. Most of the solvent was removed and the residue purified by flash chromatography on silica gel (hexane) to afford the title compound (3.5 g, 66%) as a colorless oil.[0323] 1H NMR (500 MHz, DMSO-d6): delta 2.03-2.12 (m, 2H), 2.68 (t, J= 7.5 Hz, 2H), 3.49 (t, J= 6.5 Hz, 2H), 7.19 (d, J= 8.3 Hz, 2H), 7.47 (d, J= 8.3 Hz, 2H). |
66% | With carbon tetrabromide; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 15.25h; | EXAMPLE 100. Synthesis of l-Broiotatio-4-(3-Bromo-Propyl)-Benzene (Intermediate50150[02981 To a solution of intermediate 49 (Example 99) (4.0 g, 19 mmol) in THF (30 mL)O at 0 C under the argon atmosphere was added PPh3 (6.3 g, 24 mmol) followed by CBr4 (8.0 g, 24 mmol). The mixture was stirred at the same temperature for 15 min and then stirred at room temperature for additional 15 h. Most of the solvent was removed and the residue purified by flash chromatography on silica gel (hexane) to afford the title compound (3.5 g, 66%) as a colorless oil.[0299] 1H NMR (500 MHz, DMSOd6): delta 2.03-2.12 (m, 2H), 2.68 (t, J= 7.5 Hz, 2H), 3.49 (t, J= 6.5 Hz, 2H), 7.19 (d, J= 8.3 Hz, 2H), 7.47 (d, J= 8.3 Hz, 2H). |
64% | With carbon tetrabromide; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 4h;Inert atmosphere; | Triphenylphosphine (140 mg, 534 mumol) was dissolved in 1 mL of tetrahydrofuran (THF) at 0 C, and then 3-(4-bromophenyl)propan-1-ol (100 mg, 465 mumol) and tetrabromomethane (180 mg, 543 mmol) in 1 mL of THF were added dropwise to the solution. After stirring for 4 h at room temperature under a nitrogen atmosphere, the solvent was removed in vacuo. The residue was purified by chromatography on silica gel using chloroform as the eluent to obtain compound 7 (82 mg, 64%) as yellow oil. 1H NMR (400 MHz, CDCl3): delta 2.14 (qt, J=7.0 Hz, 2H), 2.74 (t, J=7.3 Hz, 2H), 3.39 (t, J=6.6 Hz, 2H), 7.08 (d, J=8.2 Hz, 2H), 7.41 (d, J=8.2 Hz, 2H). |
With N-Bromosuccinimide; triphenylphosphine; In dichloromethane; at 20℃; for 6h;Ice-cooling; | (41-3) Synthesis of 4-bromo-1-(3-bromopropyl)benzene (compound 41-3) Compound 41-2 (3.63 g) was dissolved in methylene chloride (40 ml), triphenylphosphine (4.88 g) and N-bromosuccinimide (3.31 g) were added under ice-cooling, and the mixture was stirred under ice-cooling for 2 hr, and at room temperature for 4 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Diethyl ether (100 ml) was added, and the precipitated triphenylphosphine oxide was filtered off. The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone) to give the object product (1.87 g) as a colorless oil. 1H-NMR(CDCl3) delta (ppm): 2.10-2.17(2H, m), 2.74(2H, t, J=7.4Hz), 3.38(2H, t, J=6.5Hz), 7.08(2H, d, J=8.3Hz), 7.41(2H, dd, J=8.3, 1.9Hz). | |
With carbon tetrabromide; triphenylphosphine; In dichloromethane; at 0 - 20℃; for 18h; | General procedure: To a stirred solution of 3- or 4-substituted phenylpropanoic acid 51-63 (7.0 mmol) in dry THF (35 ml), borane dimethyl sulfide (21.0 mmol) was added dropwise at 0 oC. The reaction mixture was stirred for 18h at room temperature, quenched with H2O and concentrated in vacuo. The resulting residue was re-dissolved in diethyl ether (25 ml), and washed with 10%NaOH (30ml) and brine. The organic fraction was dried over Na2SO4, filtered, and concentrated in vacuo to give 3-phenylpropan-1-ol derivatives that were used in the next step without further purification. Triphenylphosphine (7.5 mmol) and carbon tetrabromide (7.1 mmol) were added to a stirred solution of the 3-phenylpropan-1-ol derivatives in dry CH2Cl2 at 0 oC. The reaction mixture was stirred for 18h at room temperature and quenched with brine. The organic fraction was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (10:1 n-hexane/EtOAc) to give the corresponding title compound (38-50) in a 64-73% yield (two steps). These are also all known, but commercially unavailable compounds for which the chemical structure of each could be identified from the 1H- and 13C-NMR spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | ||
95% | With 1H-imidazole In tetrahydrofuran at 20℃; for 3h; Inert atmosphere; | |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 0℃; | [3-(4-Bromo-phenyl)-propoxy]-tert-butyl-dimethyl-silane A sol. of 3-(4-bromo-phenyl)-propan-1-ol (49.4 g, 230 mmol) in DMF (500 mL) is cooled to 0° C., and imidazole (23.77 g, 349 mmol) and TBDMS-Cl (52.6 g, 349 mmol) are added. The mixture is stirred overnight, while warming up to rt. The mixture is diluted with heptane (1.0 L) and aq. sat. NH4Cl (800 mL), and the mixture is shaken. The layers are separated. The aq. layer is extracted with heptane, and the combined org. extracts are washed with brine. The org. extracts are dried over MgSO4, filtered, and the solvents are removed under reduced pressure. Purification by FC (Et2O/heptane 1:99→1:19) yields the title compound (68.1 g, 90%). LC-MS: tR=1.24 min. |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; | Compound 10; EPO A sol. of compound 9 (49.4 g, 230 mmol) in DMF (500 mL) was cooled to 0 °C, and imidazole (23.77 g, 349 mmol) and TBDMS-Cl (52.6 g, 349 mmol) were added. The mixture was stirred overnight, while warming up to rt. The mixture was diluted with heptane (1.0 L) and aq. sat. NH4Cl (800 mL), and the mixture was shaken. The layers were separated. The aq. layer was extracted with heptane, and the combined org. extracts were washed with brine. The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification by FC (Et2θ/heptane 1:99 → 1:19) yielded the title compound (68.1 g, 90%). LC-MS: tR = 1.24 min; ES+: not visible. |
With 1H-imidazole In N,N-dimethyl-formamide Yield given; | ||
With triethylamine In dichloromethane | ||
With 1H-imidazole In N,N-dimethyl-formamide for 2h; Inert atmosphere; | ||
With dmap; triethylamine In dichloromethane at 17 - 25℃; Inert atmosphere; | 1.ii (ii) (3-(4-Bromophenyl)propoxy)(tert-butyl)dimethylsilane: To a solution of the product of step (i) (32.25 g, 0.15 mol) in anhydrous dichloromethane (400mL) was added triethylamine (45 g, 0.45 mol), DMAP (915 mg, 7.5 mmol) and TBSCl (33 g, 0.215 mol) sequentially. The resulting solution was stirred overnight. The reaction mixture was extracted with dichloromethane and washed with water (x3). The combined organic layer was dried over anhydrous MgS04, filtered and concentrated in vacuo. The crude product was purified by column chromatography with PE to afford the subtitle compound (ii) as a pale brown oil (40 g). 1H-NMR(400 MHz, CDC13) δ 7.34 (d, 2H), 7.02 (d, 2H), 3.56 (t, 2H), 2.58 (t, 2H), 1.77- 1.73 (m, 2H), 0.86 (s, 9H), 0.00 (s, 6H);HPLC Retention Time = 1.017min. | |
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 13h; | 3.1 Step 1 : [3-(4-Bromophenyl)propoxy](fer?-butyl')dimethylsilane To a solution of 3-(4-bromophenyl)propan-l-ol (1 eq.) in DMF (0.25 M) was added imidazole (1.2 eq.) and tert-butyldimethylsilyl chloride (1.1 eq.). The resulting solution was stirred at RT for 13 h. The reaction mixture was quenched with sat. aq. NH4CI and extracted with hexanes. The combined organic extracts were washed further with water and brine. Concentration of the organic extracts in vacuo afforded the title compound as a colorless oil |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine In dichloromethane at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 0℃; for 0.00833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
319 g | With aluminum (III) chloride; sodium tetrahydroborate; In 1,2-dimethoxyethane; at 20 - 50℃; for 4h;Large scale; | The second step:Add M1 300g, ethylene glycol dimethyl ether 2000g, sodium borohydride 70g, and stir in a 5L reaction flask.Add 82g of aluminum trichloride in batches at room temperature, add 2 hours, the system will automatically heat up, and finally keep warm at 50 C for 2 hours.Sampling plate analysis, the reaction is over, and the reaction is stopped.Pour into ice water for hydrolysis, adjust to pH=2 with sulfuric acid, extract with ethyl acetate, wash with 10% sodium bicarbonate until neutral, separate the liquid, and steam the solvent.Obtained intermediate M2(319 g, molar yield 90%, HPLC purity 98.6%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With toluene-4-sulfonic acid In dichloromethane at 20℃; for 5h; | |
77% | With pyridinium p-toluenesulfonate In dichloromethane at 23℃; for 16h; | |
With toluene-4-sulfonic acid In dichloromethane at 20℃; for 11.5h; Large scale; | 1.3 third step: The M2 128g, 2000g of dichloromethane was added to a 5L reaction flask, and 2 g of p-toluenesulfonic acid was added at room temperature.Stir, add 3,4-dihydro-2H-pyran 60g, add 1 hour,The system temperature will rise slightly, keep warm for 30 minutes, drop to room temperature, stir for 10 hours.Sampling and analysis, after the completion of the reaction of the raw materials, washing once with 500 ml of 10% sodium hydrogencarbonate, the aqueous layer was extracted with dichloromethane, the organic phase was combined, and the solvent was evaporated.Got crude M3(180 g, HPLC purity 87%).The crude product does not need to be purified and can be used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With diisobutylaluminium hydride In toluene at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 1H-imidazole In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With borane-THF; at 20℃; for 1h; | Step 1: synthesis of 3-(4-bromophenyl)propan-1 -ol (4*)3-(4-Bromophenyl)propanoic acid (5.Og, 21 .8mmol) was treated with a 1 M solution ofBH3THF (44m1, 44mmol) and stirred at rt for lh. The mixture was diluted with a 1:1mixture of sat. aq. Rochelle?s salt and sat. aq. NaHCO3 solutions, and extracted withEtOAc. The combined organic phases were dried on Mg504, filtered and evaporatedin vacuo to yield the desired product 4* (4.71g, 100%) as a colorless liquid.1H NMR (300MHz, ODd3) 6 7.40 (d, 2H), 7.07 (d, 2H), 3.66 (t, 2H), 2.67 (t, 2H), 1 .86(quint, 2H).MS (ES) C9H11BrO requires: 213/215, (Mi-H) not found, 95%. |
99% | With borane-THF; In tetrahydrofuran; at 20℃; for 0.5h; | To a 0 C. solution of 3-(4-bromophenyl)propanoic acid (7.5 g, 32.7 mmol) and THF (100 mL) was added BH3*THF (32.7 mL of a 1 M solution in THF, 32.7 mmol) dropwise. The reaction was slowly allowed to warm to rt, then was quenched with AcOH (5 mL) and stirred for 30 min, neutralized with sat. aq. NaHCO3 (100 mL), and extracted with EtOAc (2×75 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was chromatographed (SiO2; 80 g; A=Hex, B=EtOAc; 30 min gradient from 0% B to 100% B; flow rate=60 mL/min) to afford the title compound (7.0 g, 32.5 mmol, 99% yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) delta 7.48-7.37 (m, 1H), 7.15-7.01 (m, 1H), 3.67 (t, J=6.3 Hz, 1H), 2.79-2.59 (m, 1H), 1.96-1.81 (m, 1H). |
97% | With sodium tetrahydroborate; boron trifluoride diethyl etherate; In tetrahydrofuran; at 0℃; | A round-bottom-flask was charged with <strong>[1643-30-7]3-(4-bromophenyl) propanoic acid</strong> (1.00 g, 4.37 mmol, 1 eq) dissolved in dry THF (8.8 mL). After cooling the solution to 0C NaBH4 (331 mg, 8.73 mmol, 2 eq) was added in small portions and thereafter BF3·Et2O (1.10 mL, 8.73 mmol, 2 eq) was added dropwise. The resulting mixture was stirred overnight and then quenched by slowly adding MeOH (6 mL), aqueous HCl (1 M, 5 mL) and brine (50 mL). The mixture was then extracted with EtOAc (3x50 mL), the combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude was re-dissolved in DCM and filtered over Celite to yield the product (0.92 g, 97%). 1H NMR (400 MHz, chloroform-d) delta 7.40 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 3.66 (t, J = 6.4 Hz, 2H), 2.70 - 2.61 (m, 2H), 1.92 - 1.80 (m, 2H), 1.54 (s, 1H). 13C NMR (101 MHz, chloroform-d) delta 140.88, 131.55, 130.33, 119.70, 62.10, 34.11, 31.56. |
94% | With lithium aluminium tetrahydride; In diethyl ether; at 0 - 20℃; for 3h;Schlenk technique; | An oven-dried 500 mL two-neckedround-bottom flask equipped with a Teflon-coated magnetic stirring bar, refluxcondenser and drying tube was charged with 8.56 g (37.4 mmol,1.0 eq) 3-(4-bromophenyl)propanoic acid (11). It was dissolved in 200 mL Et2O andsubsequently cooled in an ice bath to 0 C. Afterwards 2.13 g(56.1 mmol, 1.5 eq) LiAlH4 were added in small portions tothe colorless solution over a period of 5 min. The resulting greysuspension was stirred at 0 C for 10 min, afterwards the ice bathwas removed and vigorously stirred at room temperature for 3 h. Aftercomplete conversion (reaction control viaTLC), the grey suspension was again cooled in an ice bath to 0 C and180 mL 1 M HCl were added carefully. The greyish two-phase system wasextracted with EtOAc (2 x 250 mL), whereby the two layers were separatedby centrifugation. Afterwards the colorless, combined organic layers werewashed with saturated NaHCO3 (2 x 150 mL) as well as with brine(1 x 150 mL), dried over MgSO4, filtered and concentrated on arotary evaporator. Finally, the colorless, liquid crude material was purified via flash column chromatography(250 g SiO2, column: 18.0 x 6.0 cm, eluent:cyclohexane:EtOAc = 3:1 (v/v), Rf = 0.25) providing 7.53 g(35.0 mmol, 94 %) 3-(4-bromophenyl)propan-1-ol (12a) as a colorless liquid after drying under high vacuum Yield: 7.53 g (35.0 mmol, 94 %); colorless liquid.1H-NMR (300.36 MHz, CDCl3): delta = 7.39(d, 3JHH =8.3 Hz, 2H), 7.07 (d, 3JHH= 8.3 Hz, 2H), 3.65 (t, 3JHH= 6.4 Hz, 2H), 2.66 (t, 3JHH= 6.4 Hz, 2H), 1.90-1.81 (m, 2H), 1.56 (bs, 1H).13C-NMR (75.53 MHz, CDCl3): delta = 140.9 (Cq),131.5, 130.3, 119.7 (Cq), 62.1, 34.1, 31.6. |
93% | (127a) 3-(4-bromophenyl)propan-1-ol; Methyl chloroformate (1.9 mL, 24.1 mmol) was added dropwise to a tetrahydrofuran (80 mL) solution of triethylamine (3.4 mL, 24.1 mmol) and <strong>[1643-30-7]3-(4-bromophenyl) propanoic acid</strong> (5.02 g, 21.9 mmol) at 0C and the mixture was stirred at room temperature for one hour under nitrogen atmosphere. Insolubles were removed by filtration from the reaction liquid and an aqueous solution (40 mL) of sodium borohydride (1.24 g, 32.9 mmol) was added to the filtrate and the mixture was stirred at room temperature for two hours. Ethyl acetate (200 mL) was added to the reaction liquid and the organic layer was washed with a saturated saline solution (200 mL) twice, and the solvent was evaporated under reduced pressure after drying over sodium sulfate and the title compound was obtained (4.36 g, yield 93%). Colourless liquid IR (film) numax 3353, 2942, 1711, 1489, 1072, 1012, 833, 796 cm-1; 1H NMR(CDCl3, 400 MHz) delta 1.83 -1.90 (2H, m), 2.67 (2H, t, J = 7.8 Hz), 3.66 (2H, t, J = 6.3 Hz), 7.06 (2H, d, J = 8.2 Hz), 7.39 (2H, d, J = 8.2 Hz); MS (EI) m/z: 214 [M+], 196, 169, 117, 104, 91, 90, 77, 51, 50, 39. | |
93% | With lithium aluminium tetrahydride; In diethyl ether; for 16h;Reflux; | Example 130(5a,8a)-8-Hydroxy-8-isopropyl-2-(4-(3-methoxypropyl)phenyl)-2-aza-spiro[4.5]decan- 1-oneStep 1: 3-(4-Bromo-phenyl)-propan-l-olTo a suspension of 3-(4-bromophenyl)-propionic acid (3.0g, [CAS Reg. No. 1643-30-7]) in diethyl ether (50mL) was added lithium aluminium hydride (746mg) in three portions. The mixture was then heated to reflux for 16 hours. The mixture was cooled to room temperature and saturated sodium sulfate solution (3mL) was added dropwise over a period of 5 minutes. Stirring was continued for 30 minutes at RT. A white precipitation was obtained. The solid was filtered off, washed with diethyl ether and the filtrate was concentrated in vacuo to afford the title compound as a colorless liquid (2.62g, 93%) that was used without further purification. MS (EI): 215.0 [M+]. |
93% | Step 1: 3-(4-Bromo-phenyl)-propan-1-ol To a suspension of 3-(4-bromophenyl)-propionic acid (3.0 g, [CAS Reg. No. 1643-30-7]) in diethyl ether (50 mL) was added lithium aluminium hydride (746 mg) in three portions. The mixture was then heated to reflux for 16 hours. The mixture was cooled to room temperature and saturated sodium sulfate solution (3 mL) was added dropwise over a period of 5 minutes. Stirring was continued for 30 minutes at RT. A white precipitation was obtained. The solid was filtered off, washed with diethyl ether and the filtrate was concentrated in vacuo to afford the title compound as a colorless liquid (2.62 g, 93%) that was used without further purification. MS (EI): 215.0 [MH+]. | |
93% | With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 16h; | 3-(4-bromophenyl)propanoic acid (1.67 g, 7.3 mmol) was dissolved in 24 mL of THF and cooled to 0C. Borane-THF (22 mL, 22 mmol, 1.0 M THF solution) was added thereto, and the mixture was stirred at room temperature for 16hours. The reaction solution was cooled to 0C, and water and 1N HCl aqueous solution were sequentially added thereto.The reaction solution was extracted with EtOAc, and the organic layer was dried with MgSO4 and purified by columnchromatography to obtain the title compound (1.46 g, 93 %).1H-NMR (CDCl3) delta 7.40 (2H, d), 7.08 (2H, d), 3.66 (2H, m), 2.67 (2H, m), 1.86 (2H, m), 1.26(1H, t, OH) |
50.2% | <strong>[1643-30-7]3-(4-bromophenyl)propionic acid</strong> (Aldrich) (12.25 g, 53.48 mmol) was dissolved in tetrahydrofuran (100 mL) and the solution was slowly added to lithium aluminum hydride (1.22 g, 32.09 mmol) in tetrahydrofuran (100 mL). The reaction was stirred for 3h, then 150 mL 1 N aqueous sodium hydrogen carbonate was added, the mixture was extracted with ethyl acetate (3 x 150 mL) and the organic phases were dried over magnesium sulphate and concentrated in vacuo. The crude product was used without purification. Yield: 5.77 g (50.2%) 1H-NMR (300MHz, CHLOROFORM-d): delta [ppm]= 1.59 (br. s., 1H), 1.79 - 1.96 (m, 2H), 2.57 - 2.74 (m, 2H), 3.67 (t, 2H), 7.02 - 7.15 (m, 2H), 7.36 - 7.47 (m, 2H). | |
Reference Example 56; 4-[3-(tert-Butyldiphenylsilyloxy)propyl]benzyl bromide To a solution of <strong>[1643-30-7]3-(4-bromophenyl)propionic acid</strong> (1.0 g) in tetrahydrofuran (15 mL) was added borane tetrahydrofuran complex (1.0 mol/L tetrahydrofuran solution, 6.55 mL) under ice-cooling, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added 20% aqueous potassium carbonate solution under ice-cooling, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 3-(4-bromophenyl)propanol (0.93 g). The title compound was prepared in a similar manner to that described in Reference Example 55 using this material instead of 2-(4-bromophenyl)ethanol. | ||
To a suspension of lithium aluminum hydride (2.39 g, 62.9 mmol) in diethyl ether (100 mL) at 0 0C was added 3-(4-bromorhohenyl)propionic acid (9.59 g, 41.9 mmol) in THF (100 mL). After stirring at rt for 2 h, the reaction mixture was cooled to 00C and H2O (2.5 mL), NaOH (15% aq., 2.5 mL), H2O (5 mL), Et2O (200 mL), hexane (50 ml), and anhydrous Na2SO4 were added sequentially. The suspension was stirred at rt for 1 h and was filtered, and the filtrate was concentrated to afford 3-(4-bromophenyl)-propanol. | ||
Example 137. 3-(4-Bromo-phenyI)-propan-l-ol (78); [0321] To a solution of <strong>[1643-30-7]3-(4-bromo-phenyl)-propionic acid</strong> (4.0 g, 18 mmol) in THF(30 mL) at 0 C under the argon atmosphere was added LiAlH4 (1.0 M in THF; 14 mL, 14 mmol). After the addition, the ice-bath was removed and the mixture refluxed for 18 h. After cooling to room temperature, the reaction was quenched with 1 M HCl and the mixture extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated and the crude product used in the next step without further purification. | ||
Example 1 3-Amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2- carboxamide tri-hydrochloride 3HCI The title compound was prepared in accordance with the following scheme: (i) 3-(4-Bromophenyl)propan-l-ol: To a solution of 3-(4-bromophenyl)-propionic acid (9.16 g, 40 mmol) in THF (150 mL) at 0 C was added LiAlH4 (1.4 g, 36 mmol) in portionwise. When the addition was completed, the reaction mixture was heated and stirred under reflux for additional 5 hours. The reaction mixture was cooled to 0 C and 2 N-HC1 (50 mL) added dropwise. The reaction mixture was extracted with EtOAc and washed with water (x3). The combined organic extract was dried over anhydrous MgS04, filtered and concentrated in vacuo, which afforded the subtitle compound (i) as an oil (8g). 1H-NMR(400 MHz, CDC13) delta 7.40 (d, 2H), 7.08 (d, 2H), 3.66 (t, 2H), 2.66 (t, 2H), 1.89- 1.82 (m, 2H). | ||
Example 9-<4-Bromophenyl)propan-1 -ol; <strong>[1643-30-7]3-(4-bromophenyl)propionic acid</strong> (Aldrich) (12.25 g, 53.48 mmol) was dissolved in tetrahydrofuran (100 mL) and the solution was slowly added to lithium aluminum hydride (1 .22 g, 32.09 mmol) in tetrahydrofuran (100 mL). The reaction was stirred for 3h, then 150 mL 1 N aqueous sodium hydrogen carbonate was added, the mixture was extracted with ethyl acetate (3 x 150 mL) and the organic phases were dried over magnesium sulphate and concentrated in vacuo. The crude product was used without purification.Yield: 5.77 g (50.2%)1H-NMR (300MHz, CHLOROFORM-d): delta [ppm]= 1 .59 (br. s., 1 H), 1 .79 - 1 .96 (m, 2H), 2.57 - 2.74 (m, 2H), 3.67 (t, 2H), 7.02 - 7.15 (m, 2H), 7.36 - 7.47 (m, 2H). | ||
With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 70℃; for 2h;Inert atmosphere; | Under a nitrogen atmosphere L1AIH4 (0.27 g, 7.01 mmol, 1.5 eq) was added portionwise to a stirred solution of <strong>[1643-30-7]3-(4-bromophenyl)propionic acid</strong> (1.08 g, 4.70 mmol, 1 eq) in dry THF (22.0 mL) at 0 C. The reaction mixture was heated to 70 C for 2 h. After completion of the reaction, the mixture was quenched by addition of HCl 1 M drop wise at 0 C. The resulting aqueous phase was extracted with EtOAc (x3) The combined organic layers were washed with HCl 1 M (xl), sat. aq. NaHC03 (x2), brine (xl), dried over sodium sulfate and concentrated in vacuo, to give 0.97 g product as a colorless oil, which was used in the next step without further purification; yield 96%; IR (KBr) 3318, 3024, 2939, 1488, 1404, 1071, 1011, 833, 795 cm"1; 1H- MR (300 MHz, CDC13) delta 7.39 (d, J = 8.2 Hz, 2-H), 7.06 (d, J = 8.2 Hz, 2-H), 3.65 (t, J = 6.4 Hz, 2-H), 2.66 (t, J = 7.3 Hz, 2-H), 1.90-1.83 (m, 2-H), 1.65 (br s, 1-H) ppm; 1 C- MR (75 MHz, CDC13) delta 140.8, 131.4, 130.2, 119.5, 61.7, 33.9, 31.4 ppm | |
EXAMPLE 99. Synthesis of 3-(4-Bromo-Phenvn-Propan-l-ol (Intermediate 4949[0297]; To a solution of <strong>[1643-30-7]3-(4-bromo-phenyl)-propionic acid</strong> (4.0 g, 18 mmol) in THF (30 mL) at 0C under the argon atmosphere was added LiAlH4 (1.0 M in THF; 14 mL, 14 mmol). After the addition, the ice-bath was removed and the mixture refluxed for 18 h. After cooling to room temperature, the reaction was quenched with 1 M HCl and the mixture extracted with ethyl acetate. The organic layer was separated, washed with brine, <n="111"/>dried over Na2SO4 and filtered. The filtrate was concentrated and the crude product used in the next step without further purification. | ||
With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 20℃; for 18h; | General procedure: To a stirred solution of 3- or 4-substituted phenylpropanoic acid 51-63 (7.0 mmol) in dry THF (35 ml), borane dimethyl sulfide (21.0 mmol) was added dropwise at 0 oC. The reaction mixture was stirred for 18h at room temperature, quenched with H2O and concentrated in vacuo. The resulting residue was re-dissolved in diethyl ether (25 ml), and washed with 10%NaOH (30ml) and brine. The organic fraction was dried over Na2SO4, filtered, and concentrated in vacuo to give 3-phenylpropan-1-ol derivatives that were used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | In dichloromethane at 20℃; for 24h; | |
With triethylamine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: 1-Heptene; 3-(4-bromophenyl)propanol With 9-borabicyclo[3.3.1]nonane dimer In tetrahydrofuran at 20℃; Stage #2: With potassium hydroxide; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-(4-bromophenyl)propanol With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: C11H21NO4S In N,N-dimethyl-formamide at 80℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | In diethyl ether; water | 33 33A 3-(4-Bromophenyl)propan-1-ol 33A 3-(4-Bromophenyl)propan-1-ol A solution of 4-bromocinnamic acid (5.0 g, 22 mmol) in 20 ml of dry ethyl ether was added to a suspension of aluminium lithium hydride (2.49 g, 66 mmol) in dry ethyl ether (130 ml) under inert atmosphere. The reaction mixture was stirred at room temperature for 2 hours, then a NaCl saturated solution in water (80 ml) was slowly added, the two phases were separated and the aqueous one was extracted with ethyl acetate (3x50 ml). The organic extracts were dried and the solvent was evaporated off to obtain 3.60 g of the title compound as a yellowish oil (76% yield). 1H N.M.R. (300 MHz, CDCl3) δ ppm: 1.85 (m, 2H); 2.66 (t, 2H); 3.65 (t, 2H); 7.06 (d, 2H); 7.39 (d, 2H). |
With lithium aluminium tetrahydride In tetrahydrofuran for 2h; Heating; | ||
Stage #1: trans-4-bromocinnamic acid With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; Inert atmosphere; Cooling with ice; Stage #2: In tetrahydrofuran for 4h; Reflux; Inert atmosphere; | Preparation of 3-(substituted-phenyl) propan-1-ol 3 (a-g) General procedure: Yield: 23.3-88.0% .Take 3-(4-chlorophenyl)propan-1-ol (3c) for example. To a suspension of lithium aluminum hydride (1.71 g, 45 mmol) in THF (30 mL), under nitrogen atmosphere and ice bath, the solution of 2.74 g (15 mmol) 3-(4-chlorophenyl)acrylic acid (2c) in THF was gently added in 30 min. the resulting mixture stirred until it reached ambient temperature and then it was reflux for 4h. When TLC analyses indicated the disappearance of the starting material, after cooling to ambient temperature, 15 ml methanol and 15 ml water was dropped slowly to quench the reaction, then the PH was adjusted to 3 with 10% hydrochloric acid, The crude mixture was extracted with ethyl acetate (3 × 30 ml), organic layer was combined and dried over anhydrous MgSO4 and concentrated in vacuo. The resulting yellow oil was purified by chromatography on silica-gel column (n-hexane: ethyl acetate = 4:1, v/v) to obtain the product, yellow oil, yield 54.7%. 1H NMR (300 MHz, CDCl3) δ: 7.27-7.22(m, 2H), 7.15-7.10 (m, 2H), 3.66(t, J=6.4Hz, 2H), 2.68(t, J=7.44Hz, 2H), 1.91-1.81(m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: Et3N 2: lithium diisopropylamide 3: sodium hexamethyldisilazide | ||
Multi-step reaction with 3 steps 1: 64 percent / CH2Cl2 / 24 h / 20 °C 2: 83 percent / lithium diisopropylamide / tetrahydrofuran / 12 h / 65 °C 3: 91 percent / sodium hexamethyldisilazide / tetrahydrofuran / 6 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: Et3N 2: lithium diisopropylamide 3: sodium hexamethyldisilazide 4: 64 percent / (allyl)PdCp; P(t-Bu)3; NaOt-Bu / benzene-d6 / 14 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: n-BuLi / -75 °C 1.3: HCl 2.1: BH3*SMe2 | ||
Multi-step reaction with 2 steps 1.1: n-BuLi / tetrahydrofuran / 0.75 h / -78 °C 1.2: tetrahydrofuran / 20 °C 1.3: 90 percent / aq. HCl / 1 h / Heating 2.1: 99 percent / BH3-SMe2 / tetrahydrofuran / 0 - 20 °C | ||
Multi-step reaction with 2 steps 1: 82 percent / LDA / tetrahydrofuran / 1 h / -30 °C 2: 89 percent / DIBAL / toluene / 20 °C |
Multi-step reaction with 3 steps 1: sodium hydride / tetrahydrofuran 2: sodium chloride / dimethyl sulfoxide 3: diisobutylaluminium hydride | ||
Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 50 °C / Schlenk technique 1.2: 2 h / 50 °C 2.1: potassium hydroxide / water / 16 h / Schlenk technique; Reflux 2.2: 90 h / 110 °C 3.1: lithium aluminium tetrahydride / diethyl ether / 3 h / 0 - 20 °C / Schlenk technique |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 78 percent / sodium hydrogensulfate; p-hydroquinone; 4-tert-butylcatechol / diethyl ether / 3 h / 200 °C 2.1: BMS / bis-(2-methoxy-ethyl) ether / 3.5 h / 0 - 140 °C 2.2: aq. NaOH; H2O2 / 3 h / 25 - 50 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 76 percent / diethyl ether / 1 h / 20 °C 2.1: 78 percent / sodium hydrogensulfate; p-hydroquinone; 4-tert-butylcatechol / diethyl ether / 3 h / 200 °C 3.1: BMS / bis-(2-methoxy-ethyl) ether / 3.5 h / 0 - 140 °C 3.2: aq. NaOH; H2O2 / 3 h / 25 - 50 °C | ||
Multi-step reaction with 2 steps 1: CH3CO2K 2: LiAlH4 / tetrahydrofuran / 1 h / Heating | ||
Multi-step reaction with 3 steps 1: triphenylphosphine; sodium hydrogencarbonate / water / 2 h / 20 °C 2: diisobutylaluminium hydride / dichloromethane / 3 h / 0 - 20 °C 3: palladium 10% on activated carbon; hydrogen / ethyl acetate / 12 h / 20 °C |
Multi-step reaction with 2 steps 1.1: piperidine / pyridine / 6 h / 85 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 20 °C / Inert atmosphere; Cooling with ice 2.2: 4 h / Reflux; Inert atmosphere | ||
Multi-step reaction with 2 steps 1: triphenylphosphine / toluene; dichloromethane / 2 h / 20 °C 2: sodium tetrahydroborate / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 64 percent / CH2Cl2 / 24 h / 20 °C 2: 83 percent / lithium diisopropylamide / tetrahydrofuran / 12 h / 65 °C 3: 91 percent / sodium hexamethyldisilazide / tetrahydrofuran / 6 h / Heating 4: 55.3 percent / P(t-Bu)3; sodium acetate / Pd(dba)2 / dimethylformamide / 16 h / 100 - 105 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 92 percent / p-TsOH*H2O / CH2Cl2 / 5 h / 20 °C 2: nBuLi; B(O-iPr)3 / tetrahydrofuran; hexane 3: HCl; water / methanol / 3 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With potassium fluoride; N,N-phenylbistrifluoromethane-sulfonimide In tetrahydrofuran; N,N-dimethyl-formamide at 60℃; for 1h; Sealed tube; | |
Multi-step reaction with 2 steps 1: pyridine / CH2Cl2 / 0.5 h / 0 °C 2: Me4NHF2 / acetonitrile / 1 h / Ambient temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 3-(4-bromophenyl)propanol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.166667h; Stage #2: benzyl bromide In N,N-dimethyl-formamide at 20℃; for 3h; | 127.127b (127b) 1-[3-(benzyloxy)propyl]-4-bromobenzene; N,N-dimethylformamide (20 mL) solution of 3-(4-bromophenyl)propan-1-ol (4.22 g, 19.6 mmol) which was produced in Example 127 (127a) was blended with sodium hydride (55% oily, 1.03 g, 23.5 mmol) at 0°C under nitrogen atmosphere and the mixture was stirred for 10 minutes. The reaction mixture was blended with benzyl bromide (2.3 mL, 23.5 mmol) and the mixture was stirred at room temperature for three hours. The reaction liquid was cooled to 0°C, and the resultant solution was blended with water (10 mL) and ether (50 mL) and partitioned. The organic layer was washed with water (50 mL) twice and the solvent was evaporated under reduced pressure after drying over sodium sulfate. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate = 5:1) and the title compound was obtained (4.78 g, yield 80%). Colourless liquid IR (film) νmax 2941, 2858, 2384, 1488, 1455, 1364, 1102, 1073, 1012, 736, 698 cm-1; 1H NMR(CDCl3, 400 MHz) δ 1.87-1.94 (2H, m), 2.67 (2H, t, J = 7.8 Hz), 3.47 (2H, t, J = 6.3 Hz), 4.50 (2H, s), 7.04 (2H, d, J = 8.6 Hz), 7.29-7.39 (7H, m); MS (EI) m/z: 304 [M+], 225, 213, 183, 169, 117, 104, 91, 65. |
43.9% | With sodium hydroxide In dichloromethane; water | 9.b 3-(4-bromophenyl)propan-1-ol (5.77 g, 26.83 mmol) was mixed with dichloromethane (30 mL) and water (30 mL), and benzyl bromide (6.88 g, 40.24 mmol), tetra-n-butylammonium hydrogen sulfate (0.46 g, 1.34 mmol), and sodium hydroxide (5.37 g, 134.17 mmol) were added subsequently. The mixture was stirred overnight, extracted several times with dichloromethane and the combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was purified on silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated. Yield: 3.59 g (43.9%) 1H-NMR (300MHz, CHLOROFORM-d): δ [ppm]= 1.80 - 2.04 (m, 2H), 2.69 (t, 2H), 3.48 (t, 2H), 4.51 (s, 2H), 7.06 (d, 2H), 7.32 - 7.47 (m, 7H). |
With sodium hydroxide In dichloromethane; water | 9.b pyl ether; 3-(4-bromophenyl)propan-1 -ol (5.77 g, 26.83 mmol) was mixed with dichloromethane (30 mL) and water (30 mL), and benzyl bromide (6.88 g, 40.24 mmol), tetra-n- butylammonium hydrogen sulfate (0.46 g, 1 .34 mmol), and sodium hydroxide (5.37 g, 134.17 mmol) were added subsequently. The mixture was stirred overnight, extracted several times with dichloromethane and the combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The crude product was purified on silica gel using a hexane/ethyl acetate gradient, and the appropriate fractions were combined and concentrated. Yield: 3.59 g (43.9%)1H-NMR (300MHz, CHLOROFORM-d): δ [ppm]= 1 .80 - 2.04 (m, 2H), 2.69 (t, 2H), 3.48 (t, 2H). 4.51 (s, 2H), 7.06 (d, 2H), 7.32 - 7.47 (m, 7H). |
With sodium hydride In benzene for 7h; Reflux; Stirring; | 1 Reference Example 1 4-(3-Benzyloxypropyl)bromobenzene A suspension of sodium hydride (60%, 0.97 g), 3-(4-bromophenyl)-1-propanol (1.0 g) and benzyl bromide (0.69 ML) in benzene (24 ML) was stirred under reflux for 7 hours.. After cooling to room temperature, a saturated aqueous ammonium chloride solution (50ML) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (100 ML).. The organic layer was washed with water (40 ML) and brine (40 ML) and dried over anhydrous sodium sulfate.. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate = 20/1) to give 4-(3-benzyloxypropyl)bromobenzene (1.4 g).1H-NMR (CDCl3) δ ppm: 1.85-2.00 (2H, m), 2.60-2.75 (2H, m), 3.47 (2H, t, J=6.2Hz), 4.50 (2H, s), 7.00-7.10 (2H, m), 7.20-7.45 (7H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | ||
With wilkinson's In ethanol; toluene | 3-(4-bromophenyl)-propanol 3-(4-bromophenyl)-propanol To a solution under inert gas of 36.4 g of 3-(4-bromophenyl)-2-propynol (stage A) in 200 ml of ethanol at 5% of toluene, is added 200 ml of toluene, 7.9 g of Wilkinson's reagent and hydrogen at 1900 mbar for 5 hours. It is evaporated at reduced pressure until the obtainment of 45.9 g of raw product that is purified by chromatography on silica by eluding with the compound CH2Cl2/AcOEt 95/5. 30.1 g of expected product is obtained. Rf (CH2Cl2/AcOEt 95/5): 0.28 IR (CHCl3) | |
With hydrogen In toluene at 60℃; for 7h; | 41-2 (41-2) Synthesis of 3-(4-bromophenyl)-1-propanol (compound 41-2) A suspension of compound 41-1 (4.34 g) and chlorotris(triphenylphosphine)rhodium(I) (2.50 g) in toluene (170 ml) was stirred under a hydrogen atmosphere at 60°C for 7 hr. The reaction mixture was filtered through celite and concentrated. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=98:2 - 70:30) to give the object product (3.62 g) as a brown oil. 1H-NMR(CDCl3) δ (ppm): 1.28(1H, brs), 1.83-1.90(2H, m), 2.67(2H, t, J=7.7Hz), 3.67(2H, t, J=6.3Hz), 7.08(2H, d, J=8.2Hz), 7.40(2H, d, J=8.2Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With triphenylphosphine; diethylazodicarboxylate; In dichloromethane; at 20℃; for 18h; | Methyl 2,6-dihydroxybenzoate (1.002 g, 5.96 mmol), 3- (4-BROMOPHENYL) propanol (1.002 g, 4.66 mmol) and polymer supported PPh3 (2.34 mmol/g; 8.76g, 20.50 mmol) were suspended in CH2C12 (100 ml) under an inert atmosphere and cooled to 0 C. Diethyl azodicarboxylate (1. 10 ml, 6.99 mmol) was added and the mixture allowed to warm to room temperature and stirred for 18 hours. The solid was filtered off and washed with DCM (100 ml) and the solution evaporated to give an off white solid. Purification by chromatography through silica, eluent ET20 : Hexane (1: 4) gave the title compound as a white solid. Yield (381MG, 22%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | Stage #1: 1-allyl-4-bromo-benzene With borane In tetrahydrofuran at 0℃; Stage #2: With sodium hydroxide; dihydrogen peroxide In tetrahydrofuran; water at 0 - 20℃; for 3h; | 3-(4-Bromo-phenyl)-propan-1-ol BH3 (1M in THF, 412 mL, 412 mmol) is added to a sol. of 1-allyl-4-bromo-benzene (204 g, 1.03 mmol) in THF (1.00 L) under nitrogen at 0 ° C. The mixture is stirred overnight while warming up to rt. Aq. NaOH (2.5M, 1.65 L, 4.12 mol) is added, and the mixture is cooled to 0° C. H2O2 (35%, 480 mL, 5.15 mol) is dropped carefully, and the mixture is stirred for 3 h. Et2O is added, and the phases are separated. The org. layer is washed with water (1*), and brine (1*). The org. layer is dried over MgSO4, filtered, and the solvents are removed under reduced pressure. Purification by FC (Et2O/petroleum ether 1:1→Et2O) yields the title compound (97.4 g, 44%). |
44% | Stage #1: 1-allyl-4-bromo-benzene With borane In tetrahydrofuran at 0 - 20℃; Stage #2: With sodium hydroxide; dihydrogen peroxide In tetrahydrofuran; water at 0 - 20℃; for 3h; | Compound 9; BH3 (IM in THF, 412 mL, 412 mmol) was added to a sol. of compound 8 (204 g, 1.03 mmol) in THF (1.00 L) under nitrogen at 0 °C. The mixture was stirred overnight while warming up to rt. Aq. NaOH (2.5M, 1.65 L, 4.12 mol) was added, and the mixture was cooled to 0 °C. H2O2 (35%, 480 mL, 5.15 mol) was dropped carefully, and the mixture was stirred for 3 h. Et2O was added, and the phases were separated. The org. layer was washed with water (Ix), and brine (Ix). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification by FC (Et2O/petroleum ether l:l -> Et2O) yielded the title compound (97.4 g, 44%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With 1-methyl-pyrrolidin-2-one; In water; | 33B 3-(4-Cyanophenyl)propan-1-ol A mixture of 3-(4-bromophenyl)propan-1-ol (2.0 g, 9.3 mmol), copper (I) cyanide (1.49 g, 16.7 mmol) and N-methylpyrrolidinone (13 ml) was stirred at 200°C for 2.5 hours. After that the reaction mixture was cooled at room temperature, poured onto a solution of diethylamine (30 g) and water (80 ml) and extracted with ethyl acetate (3x40 ml). The combined organic phases were dried and volatiles were removed, to obtain an oil from which N-methylpyrrolidinone was removed by distillation under high vacuum (0.5 torr, 85°C), thereby obtaining 0.78 g of the title compound (52percent yield). 1H N.M.R. (300 MHz, CDCL3) delta ppm: 1.85 (m, 2H); 2.42 (s broad, 1H); 2.76 (t, 2H); 3.64 (t, 2H); 7.29 (d, 2H); 7.53 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: methyl (E)-4-bromocinnamate With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 4h; Stage #2: With water In tetrahydrofuran at 0℃; | 2.1 Step 1 : 3-(4-Bromophenyl)propan-l-olTo a THF solution (0.5 M) of methyl (2£)-3-(4-bromophenyl)acrylate (1 eq.) was added, at 0 0C, lithium aluminum hydride (1.0 M THF solution, 1 eq.) dropwise over a period of for 3 h. The reaction mixture was then warmed slowly to RT over I h. At 0 0C, the reaction was carefully quenched with freshly-deoxygenated H2O. The organic layer was separated and washed with cold 10% aq. HCl. The aqueous washes were combined and back-extracted with ether. The organic extracts were then washed further with sat. aq. NaHCO3 and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo to reveal a yellow oil. Purification by way of full vacuum distillation afforded the title compound as a colorless oil |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tributylphosphine; 1,1'-azodicarbonyl-dipiperidine In toluene at 80℃; for 2h; | 2.2 Step 2: 2-[3-(4-Bromophenyl)propoxy]-3-chloro-l,4-difluorobenzene3-(4-Bromophenyl)propan-l-ol from the previous step (1 eq.) and 2-chloro-3,6- difluorophenol (1 eq.) were taken up in freshly deoxygenated toluene (0.3 M). To this solution was then added l , r-(azodicarbonyl)-dipiperidine (1.2 eq.) and finally tributylphosphine (1.2 eq.). The resulting yellow solution was heated at 80 0C for 2 h. The reaction mixture was cooled to RT, diluted with ether, and washed with 1 N aq. NaOH. The aqueous wash was back extracted with ether and the combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a EPO yellow semi-solid. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex - > 15: 1 (v/v) Hex : EtOAc) afforded the title compound as a colorless oil |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium acetate In 1,4-dioxane at 100℃; Inert atmosphere; | 3-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-1-ol (108) A round-bottom-flask was charged with 3-(4-bromophenyl)propan-1-ol (88) (916 mg, 4.26 mmol, 1 eq), bis (pinacolato)diboron (1.63 g, 6.39 mmol, 1.5 eq), potassium acetate (2.09 g, 21.29 mmol, 5 eq) and [1,1′-bis (diphenylphosphino) ferrocene]dichloropalladium (174 mg, 0.21 mmol, 0.05 eq). The flask was put under argon atmosphere and after the reactants were suspended in 1,4-dioxane (22 mL) the mixture was heated to 100°C overnight and then concentrated under reduced pressure. The residue was purified via flash-column-chromatography (SiO2, 0% to 20% EtOAc in pentane) to yield the product (1.03 g, 92%). 1H NMR (400 MHz, chloroform-d) δ 7.74 (d, J = 7.4 Hz, 2H), 7.22 (d, J = 7.4 Hz, 2H), 3.66 (t, J = 6.3 Hz, 2H), 2.72 (t, J = 7.6 Hz, 2H), 1.89 (p, J = 6.7 Hz, 2H), 1.34 (s, 12H). 13C NMR (101 MHz, chloroform-d) δ 145.40, 135.09, 128.05, 83.80, 62.35, 34.20, 32.40, 24.98. |
With potassium acetate In dimethyl sulfoxide at 80℃; | B A mixture of 3-(4-bromophenyl)propanol (8.15 g, 37.9 mmol), potassium acetate (11.2 g, 113.7 mmol), bis(pinacolato)diboron (10.6 g, 41.7 mmol), dimethyl sulfoxide (150 mL) and 1, l '-bis(diphenyl-phosphino) ferroncene-palladium dichloride dichloromethane complex (1:1) (1.55 g, 1.89 mmol) was heated at 800C under nitrogen overnight. Upon cooling, the reaction mixture was poured into water (-300 mL), and the product was extracted with Et2O-hexanes (1:1) (3x300mL). The combined organic extracts were washed with water (~300 mL), brine, dried (Na2SO4) and concentrated to afford 3-[4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl]propanol, which was used without further purification. | |
With potassium acetate In dimethyl sulfoxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With pyridine; formic acid; isocyanate de chlorosulfonyle In dichloromethane | |
80% | With formic acid; isocyanate de chlorosulfonyle; triethylamine In dichloromethane at 0 - 25℃; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | |
66% | Stage #1: 3-(4-bromophenyl)propanol With 1H-imidazole; chloro-diphenylphosphine In toluene at 20℃; Inert atmosphere; Stage #2: With iodine In toluene at 20℃; Inert atmosphere; | |
62% | With 1H-imidazole; iodine; triphenylphosphine In diethyl ether; acetonitrile at 0 - 20℃; for 0.75h; Inert atmosphere; |
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium tetrahydroborate In decaethylene glycol at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 22 - 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 22 - 25℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: 3-(4-bromophenyl)propanol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 20℃; | 130.2 Step 2: l-Bromo-4-(3-methoxy-propyl)-benzene3-(4-Bromo-phenyl)-propan-l-ol (2.60g, obtained in example 130, step 1) was dissolved in THF (35mL). The mixture was cooled to 0°C and sodium hydride (60% in mineral oil, 967mg) was added in four portions to the cold mixture. Stirring was continued at 0°C for 1 hour. Then, iodomethane (1.13mL) was added dropwise over a period of 15 minutes to the reaction mixture. The mixture was warmed to room temperature over a period of 1 hour. The reaction mixture was poured into ice/water and was extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2S04, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a light yellow liquid (2.61g, 94%). MS (EI): 229.0 [M+]. |
94% | Stage #1: 3-(4-bromophenyl)propanol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 1h; Stage #2: methyl iodide In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.25h; | 130.2 Step 2 : 1-Bromo-4-(3-methoxy-propyl)-benzene 3-(4-Bromo-phenyl)-propan-1-ol (2.60 g, obtained in example 130, step 1) was dissolved in THF (35 mL). The mixture was cooled to 0° C. and sodium hydride (60% in mineral oil, 967 mg) was added in four portions to the cold mixture. Stirring was continued at 0° C. for 1 hour. Then, iodomethane (1.13 mL) was added dropwise over a period of 15 minutes to the reaction mixture. The mixture was warmed to room temperature over a period of 1 hour. The reaction mixture was poured into ice/water and was extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a light yellow liquid (2.61 g, 94%). MS (EI): 229.0 [M-]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; | |
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 5℃; for 1h; Inert atmosphere; | 2.i Example 2 3-Amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine- carboxamideThe title compound was prepared in accordance with the following scheme:(i) 3-(4-Bromophenyl)propyl methanesulphonate:To a stirred solution of 3-(4-Bromophenyl)propan-l-ol (500 g, 2.30 mol) anddiisopropylethylamine (312 g, 2.40 mol) in anhydrous dichloromethane (4 L) at 0~5°C was added dropwise methanesulphonyl chloride (280 g, 2.40 mol) slowly. After addition, the reaction mixture was stirred for 1 hour at 0~5°C. The reaction mixture was washed with brine (1 L) twice. The organic phase was concentrated in vacuo to afford the subtitle compound (i) (667 g). HPLC Retention Time = 1.353 min. | |
With triethylamine In dichloromethane at 0℃; for 2h; | 25.B Step B: 3-(4-bromophenyl)propyl methanesulfonate 3-(4-bromophenyl)propan-1-ol (1.07 g, 4.97 mmol) obtained in Step A was dissolved in DCM (12 mL). TEA(1.04 mL, 7.46 mmol) was added thereto, and methanesulfonyl chloride (0.46 mL, 5.96 mmol) was then slowly addedthereto at 0°C. The mixture was stirred for 2 hours. After termination of the reaction, the reaction solution was dilutedwith water at 0°C, washed with 1N HCl and extracted with DCM. The organic layer was dried with anhydrous magnesiumsulfateto obtain 1.4 g of the title compound, which was used in the next step without purification. |
With triethylamine In chloroform at 20℃; for 2.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With Dess-Martin periodane; In dichloromethane; at 20℃; for 2h; | Example A.4: Synthesis of 3-(4-bromophenyl)propanal (10*) Alcohol 4* (4.71g, 21.8mmol) was dissolved in DCM, treated with Dess-Martin periodinane (9.71g, 20.9mmol) and stirred at rt for 2h. The mixture was quenchedwith 2M NaOH, the phases were separated the aqueous layer extracted with DCM. The combined organic phases were dried on Mg504, filtered and evaporated in vacuo. The crude was purified by flash chromatography on silica gel using a gradient of DCM in cHex to yield the desired product 10* (4.46g, 96%) as a colourless liquid.1H NMR (400MHz, CDCI3) 6 9.81 (5, 1H), 7.41 (d, 2H), 7.07 (d, 2H), 2.91 (t, 2H),2.79-2.74 (m, 2H).MS (ES) C9H9BrO requires: 211/213, (Mi-H) not found, 100%. |
86% | Oxalyl chloride (0.599 mL, 6.973 mmol) was dissolved in DCM (15 mL), and DMSO (0.99 mL, 13.94 mmol)dissolved in DCM (10 mL) was slowly added thereto at -78C. The mixture was stirred for 15 minutes, and 3-(4-bromophenyl)propan-1-ol (1.0 g, 4.64 mmol) dissolved in DCM (10 mL) was slowly added thereto at -78C. The mixture was stirredfor 30 minutes, and TEA (1.96 mL) was slowly added thereto at -78C. The temperature was slowly increased to roomtemperature, and the reaction solution was stirred for 3 hours. After termination of the reaction, the reaction solutionwas diluted with water and extracted with DCM. The organic layer was dried with anhydrous magnesiumsulfate andpurified by column chromatography (eluent, EtOAc/Hex = 1/5) to obtain the title compound (0.859 g, 86%).NMR: 1H-NMR (CDCl3) delta 9.81(1H, s), 7.40 (2H, d), 7.07(2H, d), 2.91(2H, m), 2.77(2H, t) | |
76.9% | With pyridinium chlorochromate; In dichloromethane; at 0 - 20℃; for 4h; | 3-(4-Bromophenyl) propan-1-ol (4 g, 18.5 mmol, 1.0 equiv) was dissolved into dichloromethane (60 mL) and cooled to 0C. PCC (5.21 g, 24.1 mmol, 1.5 equiv) was added in portions and the reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was filtered through celite bed and the filtrate was concentrated to afford a crude residue. The crude residue was purified by silica gel column chromatography (10-20 % diethyl ether/n-pentane) to afford the desired product 5.21a (3.05 g, 76.9 % yield). 1H NMR (400 MHz, CDCI3) 69.83 (s, 1H), 7.43 (d, J = 8.3 Hz, 2H), 7.10 (d, J 8.2 Hz, 2H), 2.94 (t, J 7.3 Hz, 2H), 2.79 (t, J 7.4 Hz, 2H). |
58.5% | With sodium hydrogencarbonate; Dess-Martin periodane; In dichloromethane; at 0 - 20℃; | To a 0 C. mixture of 26A (7 g, 32.5 mmol) and NaHCO3 (3.28 g, 39.1 mmol) in DCM (200 mL) was added Dess-Martin periodinane (16.56 g, 39.1 mmol) and the reaction was allowed to slowly warm to rt overnight. The reaction was diluted with sat. aq. NaHCO3 (150 mL) and extracted with DCM (50 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was chromatographed (SiO2; 80 g; A=Hex, B=EtOAc; 20 min gradient from 0% B to 40% B; flow rate=60 mL/min) to afford the title compound (4.06 g, 19.1 mmol, 58.5% yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) delta 9.82 (t, J=1.2 Hz, 1H), 7.48-7.37 (m, 2H), 7.19-6.97 (m, 2H), 3.02-2.88 (m, 2H), 2.83-2.70 (m, 2H). |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 1h; | General procedure: Yield: 44.2-90.3 %. Take 3-(4-chlorophenyl)propanal (4c) for example. To a mixture of pyridinium chlorochromate (PCC) (2.55 g, 11.8 mmol) and dichloromethane (50 mL), the corresponding alcohol 3-(4-chlorophenyl)propan-1-ol (1.4 g, 8.21 mmol) was added. The resulting mixture was stirred for 1 h under ambient temperature, when TLC analyses indicated the disappearance of the starting material. The mixture was filtered over silica gel under vacuum, washing with dichloromethane. The solvent was totally removed under reduced pressure, resulting in a yellow oil, which was purified by column chromatography on silica-gel column (n-hexane: ethyl acetate = 3:1, v/v) to obtain the product, yellow oil, yield 44.2 %. 1H NMR (300 MHz, CDCl3) delta 9.81 (t, J=1.2Hz, 1H), 7.28-7.23 (m, 2H), 7.16-7.07 (m, 2H), 2.92 (t, J=7.4Hz, 2H), 2.77 (dt, J=7.2Hz, 1.2Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate In 1,4-dioxane | 1.2 1.2 1.2 3-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propan-1-ol 26.5 g (0.123 mol) of 3-(4-bromophenyl)propan-1-ol and 36.0 g (0.139 mol) of bis(pinacolato)diboron are dissolved in 400 ml of dioxane and, after addition of 36.5 g (0.372 mol) of potassium acetate and 2.80 (3.82 mmol) of [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride, heated under reflux overnight. The batch is subsequently acidified using dil. hydrochloric acid and extracted three times with MTB ether. The combined org. phases are washed with water, dried over sodium sulfate and evaporated in vacuo. The residue is filtered through silica gel with heptane/MTB ether (4:1), and residues of bis(pinacolato)diboron are removed at 160° C. in a fine vacuum, giving 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propan-1-ol as a yellow oil which is sufficiently pure for further reactions. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(triphenylphosphine)palladium(II)-chloride In tetrahydrofuran; ethyl acetate | 2.3 2.3 7.0 g (32.5 mmol) of 3-(4-bromophenyl)propan-1-ol are initially introduced in 70 ml of THF and 30 ml of diisopropylamine, and, after addition of 1.0 g (1.4 mmol) of bis(triphenylphosphine)palladium(II) chloride and 0.4 g (2.1 mmol) of copper(I) iodide, 16.4 g (50.5 mmol) of (6-ethynylnaphthalen-2-yloxy)triisopropylsilane in 30 ml of THF are added dropwise at 70° C. The batch is left to stir for 5 h at 70° C., 200 ml of ethyl acetate are added, and the mixture is washed three times with water. The combined aqueous phases are extracted with ethyl acetate, and the combined org. phases are dried over sodium sulfate and evaporated in vacuo. Chromatography of the crude product on silica gel with firstly toluene and then toluene/ethyl acetate (7:3) gives 2-triisopropylsilanyloxy-6-trimethylsilanylethynylnaphthalene as a brown oil, which is employed in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40 mg | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane at 90℃; for 0.5h; | 80.1 6-chloro-5-[4-(3-hydroxypropyl)phenyl]-1H-indole-3-carbaldehyde To a solution of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (100 mg, 0.379 mmol) in dioxane (2 mL) and DMF (0.1 mL) was added N,N-dimethylformiminium chloride (180 mg, 0.36 mmol). The resulting mixture was stirred at room temperature for 20 min. The reaction was quenched with 2.0 N potassium carbonate (1.5 mL, 3.0 mmol), then 3-(4-bromophenyl)propan-1-ol (81.5 mg, 0.379 mmol) and Pd(dppf)Cl2 (28 mg, 0.037 mmol) were added, then heated to 90° C. for 30 min. The reaction mixture was extracted with EtOAc (3 mL*3), combined the organic layers and concentrated in vacuo to afford the title compound (40 mg, 27% yield) after purification via preparative TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 3-(p-isopropylphenyl)propionic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 45℃; for 0.25h; Inert atmosphere; Stage #2: 3-(4-bromophenyl)propanol With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 45℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: 3-(4-methoxyphenyl)propanoic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 45℃; for 0.25h; Inert atmosphere; Stage #2: 3-(4-bromophenyl)propanol With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 45℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Stage #1: 3-(4-chlorophenyl)propanoic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 45℃; for 0.25h; Inert atmosphere; Stage #2: 3-(4-bromophenyl)propanol With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 45℃; for 6h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With di-isopropyl azodicarboxylate; triphenylphosphine at 20 - 24℃; Inert atmosphere; Cooling with ice; | 59 Preparation of 2-(3-(4-bromophenyl)propyl)isoindoline-1,3-dione (C56) To 3-(4-bromophenyl)propan-1-ol (4.70 g, 21.9 mmol), isoindoline-1,3-dione (3.54 g, 24.0 mmol) and triphenylphosphine (6.88 g, 26.2 mmol) in a 500 mL round bottomed flask equipped with a stir bar, nitrogen, and addition funnel, and cooled in an ice water bath was added diisopropyl azodicarboxylate (5.10 mL, 26.2 mmol). The reaction was allowed to warm to room temperature over the weekend. The reaction mixture was adsorbed onto Celite. Purification by flash column chromatography using 5-20% ethyl acetate/hexanes as eluent provided a solid which was dried overnight at 50° C. in vacuo to afford the title compound as a white solid (6.51 g, 87%): mp 88-90° C., 1H NMR (400 MHz, CDCl3) δ 7.86-7.79 (m, 2H), 7.71 (dd, J=5.5, 3.0 Hz, 2H), 7.38-7.32 (m, 2H), 7.11-7.04 (m, 2H), 3.73 (t, J=7.1 Hz, 2H), 2.68-2.59 (m, 2H), 2.07-1.96 (m, 2H); ESIMS m/z 346 [(M+2)+]. |
With triphenylphosphine In ethyl acetate | 9 Preparation of 2-(3-(4-bromophenyl)propyl)isoindoline-1,3-dione (C3) Example 9 Preparation of 2-(3-(4-bromophenyl)propyl)isoindoline-1,3-dione (C3) To 3-(4-bromophenyl)propan-1-ol (4.70 g, 21.9 mmol), isoindoline-1,3-dione (3.54 g, 24.04 mmol) and triphenylphosphine (6.88 g, 26.2 mmol) in a 500 mL round-bottomed flask equipped with a stir bar, nitrogen, and addition funnel cooled in an ice water bath was added diisopropyl azodicarboxylate (5.10 mL, 26.2 mmol). The reaction was allowed to warm to room temperature over the weekend. The reaction mixture was adsorbed onto Celite. Purification by flash column chromatography using 5-20% ethyl acetate/hexanes as eluent provided a solid which was dried overnight at 50° C. at about 25 in. Hg providing the title compound as a white solid (6.51 g, 87%): mp 88-90° C.; 1H NMR (400 MHz, CDCl3) δ 7.86-7.79 (m, 2H), 7.71 (dd, J=5.5, 3.0 Hz, 2H), 7.38-7.32 (m, 2H), 7.11-7.04 (m, 2H), 3.73 (t, J=7.1 Hz, 2H), 2.68-2.59 (m, 2H), 2.07-1.96 (m, 2H); ESIMS m/z 346 ([M+2]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 3-(4-bromophenyl)propanol With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: With sodium azide In N,N-dimethyl-formamide at 50℃; for 24h; Inert atmosphere; | 55 Preparation of l-(3-azidopropyl)-4-bromobenzene (55) Under a nitrogen atmosphere, DPPA (diphenylphosphoryl azide) (2 eq) and l,8-Diazabicycloundec-7-ene (DBU) (2 eq) were subsequently added to a cooled (0° C) solution of the corresponding alcohol (4) (1 eq) in dry Ν,Ν'- dimethylformamide (0.4 M). After 0.5 h. NaN3 (2 eq) was added and the reaction mixture was heated for 3 h. at 100 °C. After cooling to room temperature, the reaction was worked up by dilution with water and extraction with diethyl ether (x5). The combined organic layers were washed with water (x2), brine (xl), dried over sodium sulfate and concentrated in vacuo. Finally the crude material was purified by column chromatography to give the desired azide 3-(l-(8-azidooctyl)-lH-l,2,3-triazol-4-yl)pyridine ; The title compound was prepared from (54) according to the general procedure of example 5, but the reaction mixture was heated to 50 °C for 24 h. The crude material was purified by column chromatography using PE/EtOAc 98:2 as eluant, to give a colorless oil; yield 79%; IR (KBr) 2941, 2097, 1488, 1254, 1072, 1011, 831, 795 cm"1; 1H- MR (300 MHz, CDC13) δ 7.41 (dd, J = 6.4/1.8 Hz, 2-H), 7.06 (dd, J = 6.4/1.8 Hz, 2-H), 3.28 (t, J= 6.7 Hz, 2-H), 2.66 (t, J = 7.3 Hz, 2-H), 1.88(quint, J = 6.7 Hz, 2-H) ppm; 1 C-NMR (75 MHz, CDC13) δ 139.9, 131.7, 130.3, 120.0, 50.6, 32.2, 30.4 ppm. |
Stage #1: 3-(4-bromophenyl)propanol With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: With sodium azide In N,N-dimethyl-formamide at 50℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Methyldicyclohexylamine; palladium diacetate; triphenylphosphine In ethanol at 80℃; Inert atmosphere; | Intermediate I.1 A mixture of 3-(4-bromophenyl)propan-1-ol (5.0 g; 23.25 mmol), diethyl phosphite (3.85 g; 27.90 mmol) N-methyldicyclohexylamine (7.40 ml; 34.87 mmol), triphenylphosphine (0.37 g; 1.39 mmol) and palladium acetate (0.10 g; 0.46 mmol) in ethanol (10 ml) and argon atmosphere is stirred at 80° C. over night. The mixture is evaporated and the residue is taken up in water and extracted with ethyl acetate. The organic layer is separated, dried and evaporated. The residue is purified by silica gel column chromatography (gradient: DCM/methanol 0-5%). C13H21O4P ESI Mass spectrum: m/z=273 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Methyldicyclohexylamine; palladium diacetate; triphenylphosphine In ethanol at 80℃; Inert atmosphere; | Intermediate I.1 Intermediate I.1A mixture of 3-(4-bromophenyl)propan-1 -ol (5.0 g; 23.25 mmol), diethyl phosphite (3.85 g; 27.90 mmol) /V-methyldicyclohexylamine (7.40 ml; 34.87 mmol), triphenylphosphine (0.37 g; 1.39mmol) and palladium acetate (0.10 g; 0.46 mmol) in ethanol (10 ml) and argon atmosphere is stirred at 80°C over night. The mixture is evaporated and the residue is taken up in water and extracted with ethyl acetate. The organic layer is separated, dried and evaporated. The residue is purified by silica gel column chromatography (gradient: DCM / methanol 0-5%). C13H21O4P ESI Mass spectrum: m/z = 273 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With copper(l) iodide; sodium azide; sodium 2-(1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-3-olate; N,N-dimethylethylenediamine In diethyl ether at 100℃; for 2h; Inert atmosphere; Schlenk technique; | Generalprocedure for the Buchwald-Finkelstein reaction General procedure: An evacuated and argon purged 250 mLthree-necked round-bottom flask equipped with a Teflon-coated magnetic stirringbar, argon inlet, reflux condenser and gas bubbler was charged with30.0 mmol (1.0 eq) 4-bromoaryl derivative. It was dissolved in60 mL degassed EtOH:H2O = 7:3 (v/v) under argon and 3.90 g(60.0 mmol, 2.0 eq) NaN3, 297 mg (1.50 mmol, 5.0 mol %)sodiumascorbate, 571 mg (3.00 mmol, 10 mol%) as well as 485 µL (397 mg,4.50 mmol, 15 mol%) N,N’-dimethylethylenediamine(DMEDA) were added, respectively. The bluish suspension wasadditionally degassed for three times applying vacuum to the suspension untilthe solvent started to boil, which was immediately afterwards purged withargon. It was heated under reflux in an oil bath at 100 °C for 2 huntil reaction control via GC-MSshowed quantitative conversion of the starting material. Subsequently, the bluishsuspension was cooled to room temperature and the solvent was removed on arotary evaporator. The residual, brownish solid was diluted with 300 mLEtOAc and the organic phase was washed with 1 M HCl (2 x 150 mL).Afterwards the product was re-extracted from the brownish, aqueous phase withEtOAc (1 x 50 mL), the combined brownish, organic phases were washed withhalf-saturated NaHCO3 (2 x 150 mL) and again re-extracted withEtOAc (1 x 50 mL). The combined yellowish, organic phases were dried overMgSO4, filtered, and concentrated on a rotary evaporator. Finally, the brownish, viscous liquid was purified via flash column chromatography(250 g SiO2, column: 22.0 x 6.0 cm) and the resultingyellowish liquid dried under high vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With (S)-diphenylprolinol; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dimethyl sulfoxide; acetonitrile at 20℃; for 7h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.4% | With tetrabutyl-ammonium chloride; sodium hydroxide In toluene | 27.27A tert-Butyl 2-(3 -(4-bromophenyl)propoxy)acetate To a 0 °C mixture of 3-(4-bromophenyl)propan-1-ol (3.0 g, 14.0 mmol) and Bu4NC1.H20 (1.94 g, 6.97 mmol) in toluene (100 mL) was added NaOH (22.3 mL of a 30% w/v aq. solution; 167 mmol) followed by tert-butyl 2-bromoacetate (3.79 mL, 25.6mmol). The reaction was stirred vigorously overnight, then was diluted with water (100 mL) and extracted with EtOAc (2x50 mL). The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. The residue was chromatographed (Si02 80 g; A = Hex, B = EtOAc; 15 mm gradient from 0% B to 50% B; flow rate = 60 mL/min) to afford the title compound (2.45 g, 7.44 mmol, 5 3.4% yield)as a colorless oil. 1H NMR (400 MHz, CD2C12) ö 7.47 - 7.41 (m, 2H), 7.14 (d, J8.6 Hz,2H), 3.95 (s, 2H), 3.53 (t, J=6.3 Hz, 2H), 2.74 - 2.67 (m, 2H), 1.96 - 1.86 (m, 2H), 1.50 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 1,2-bis(t-butyloxycarbonyl)hydrazine; 3-(4-bromophenyl)propanol With (2S)-2-{diphenyl[(trimethylsilyl)oxy]methyl}pyrrolidine; 2,6-dimethylpyridine; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(I) bromide In acetonitrile at 20℃; for 72h; Stage #2: In methanol; acetonitrile at 0℃; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | Stage #1: 3-(4-bromophenyl)propanol With n-butyllithium In tetrahydrofuran at -78℃; for 5h; Stage #2: 2-methyl-1,2-epoxypropane In tetrahydrofuran at -50℃; for 0.5h; Stage #3: With boron trifluoride diethyl etherate In tetrahydrofuran at -50℃; for 1.5h; | 1.1 Step 1: 3-[4-(2-hydroxy-2-methylpropyl)phenyl]propanol To a solution of 3-(4-bromophenyl)propan-l-ol (22.8 g, 106 mmol, 1 equiv.) in THF (1.06 L) at -78°C was added w-BuLi (1.6 M, 358 mL, 573 mmol, 5.4 equiv.) dropwise. After stirring at -78°C for 5 hours, the temperature was allowed to reach -50°C and isobutylene oxide (47.1 mL, 530 mmol, 5 equiv.) was added dropwise. After stirring at -50°C for 30 min, boron trifluoride etherate (101 mL, 796 mmol, 7.5 equiv.) was added dropwise. After stirring at -50°C for lh30, the reaction was quenched with a 10% w/w solution of Na/K tartrates and the mixture was allowed to reach room temperature overnight. It was extracted three times with ether, the combined organic extracts were dried over sodium sulfate and the solvent was evaporated. Lighter impurities were removed by bulb-to-bulb distillation (100-120°C, 10 mbar) to afford 3-[4-(2-hydroxy-2- methylpropyl)phenyl]propanol as an oil (11.5 g, 52 % yield) that solidified upon standing. 1H NMR: 1.22 (s, 6H), 1.44 (s, 2H), 1.85-1.92 (m, 2H), 2.65-2.73 (m, 2H), 2.73 (s, 2H),3.67 (t, / = 6.4, 2H), 7.12-7.14 (m, 4H). 13C NMR: 140.0 (s), 135.2 (s), 130.5 (d, 2C), 128.3 (d, 2C), 70.8 (s), 62.3 (t), 49.3 (t), 34.2 (t), 31.7 (t), 29.2 (q, 2C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate In 1,4-dioxane at 20 - 100℃; for 18h; Inert atmosphere; | 41A 41A. 3-(2'-Fluoro-5'-isopropoxy-[1 ,1 '-biphenyl]-4-yl)propan-1-ol To a solution of 3-(4-bromophenyl)propan-1-ol(1.5 g, 6.97 mmol) in dioxane (20 mL) was added (2-fluoro-5-isopropoxyphenyl)boronic acid (1.381 g, 6.97 mmol),Pd(Ph3P)4 (0.806 g, 0.697 mmol), and Cs2C03 (2.95 g, 9.07mmol). The mixture was degassed and charged with Ar. Themixture was stirred under Ar for 10 hat 100° C., then cooledtort and stirred for 8 hat rt, after which sat'd aq. NaHC03was added. The aqueous layer was extracted with EtOAc(2x). The combined organic extracts were dried over MgS04and concentrated in vacuo. The residue was chromatographed(Si02 ; 40 g; Et0Ac/Hexane=1/4) and then purifiedby preparative HPLC (PHENOMENEX 30x100 mmAxiaLuna column with 65-100% B over 10 min, A=90:10:0.1H20:MeOH:TFA and 8=90:10:0.1 MeOH:H20:TFA) togive the title compound (1.62 g, 5.34 mmol, 77% yield). 1HNMR (400 MHz, CDC13 ) ll7.54-7.45 (m, lH), 7.36-7.29 (m,lH), 7.08 (dd, 1=10.1, 9.0 Hz, lH), 6.98 (dd, 1=6.4, 3.1 Hz,lH), 6.85 (dt, 1=9.0, 3.5 Hz, lH), 4.55 (dt, 1=12.1, 6.1 Hz,lH), 3.77 (t, 1=6.5 Hz, 2H), 2.85-2.71 (m, 2H), 1.97 (dd,1=7.8, 6.7 Hz, 2H), 1.36 (d, 1=5.9 Hz, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 3-(4-bromophenyl)propanol; aniline With lithium hexamethyldisilazane In toluene for 0.5h; Inert atmosphere; Stage #2: With tris-(dibenzylideneacetone)dipalladium(0); tri tert-butylphosphoniumtetrafluoroborate In toluene at 100℃; for 17h; Inert atmosphere; | 1 An oven dried 1 L round bottom flask equipped with a reflux condenser, magnetic stir bar and gas inlet/outlet valves was charged with 3-(4-bromophenyl)propan-1-ol (17.2 g, 80 mmoles) and aniline (3.72 g, 40 mmoles). A solution of 1M lithium bis trimethylsilylamide in toluene (200 mL, 200 mmoles) was then added via cannula transfer. The resulting dark brown slurry was stirred under nitrogen for 30 minutes. Under a strong stream of nitrogen, Pd2(dba)3 (183 mg, 0.2 mmoles), and tri-tert-butylphosphonium tetrafluoroborate (174 mg, 0.6 mmoles) were added at once. The stopcock was immediately replaced and the flask was heated to 100° C. under nitrogen. After about 30 minutes, solid particles began appearing in the rapidly stirring mixture. The reaction was allowed to proceed overnight. The next morning, evenly distributed brown particles were observed. These particles had not collected on the walls of the flask. The reaction was allowed to proceed for a total time of 17 h. The flask was cooled and 200 mL of toluene was added to the flask. Aqueous HCl (2M, 200 mL) was added dropwise to the vigorously stirring mixture. During the addition, the solid slowly dissolved. The resulting two-phase mixture was neutralized using a saturated solution of NaHCO3. The organic layer was separated and washed with 2*200 mL of water, and 3*3 300 mL of brine. The resulting dark brown solution was filtered through a short bed of Celite and dried over MgSO4. The mixture was filtered to remove the MgSO4 and solvent was removed under vacuum to give the triphenylamine comprising two propyl alcohol groups as a dark brown viscous liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium hydroxide at 120℃; for 24h; Sealed tube; Autoclave; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; triphenylphosphine at 65 - 70℃; for 6h; Inert atmosphere; | 4.2 Step 2: Synthesis of Intermediate 2 The raw material p-bromophenylpropanol (10.7g, 50mmol) and triethylamine were added to a three-vial flask equipped with a constant pressure dropping funnel, a spherical condenser tube, and a thermometer, and after sufficient nitrogen replacement,Bis(triphenylphosphine)dichloropalladium (0.35 g, 1%), cuprous iodide (0.28 g, 3%), and triphenylphosphine (0.9 g, 3%) were added to the system.Trimethylsilyne was added to the dropping funnel and nitrogen gas was replaced again.After that, the system was heated to 65°C and trimethylsilylne was added dropwise.During the addition, the internal temperature of the system was maintained at 65-70°C, and the reaction was continued for 6 hours after the addition was completed until sufficient conversion occurred.After the work-up process, the triethylamine salt was filtered off with suction and the triethylamine was evaporated under reduced pressure to give a black oil.After adding heptane, it was washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to give a black oil. The product of the previous step and ethanol were added to a single-mouth flask, KOH (0.84 g, 15 mmol) was added, and the flask was thoroughly replaced with nitrogen.The reaction was sampled under magnetic stirring for 1 hour until the reaction was completed.After the work-up, ethanol was distilled off under reduced pressure, and after addition of n-heptane, the mixture was washed with water to remove KOH until neutral, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to obtain a black oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 20℃; for 12h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tetramethylammonium formiate; triphenylphosphine In water; N,N-dimethyl-formamide at 80℃; for 4h; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; N,N-dimethyl-formamide at 85℃; for 2.5h; Inert atmosphere; | 3-(4-(Pyridin-3-yl)phenyl)propan-1-ol (89) A round-bottom-flask was charged with 3-(4-bromophenyl)propan-1-ol (88) (406 mg, 1.89 mmol, 1 eq), pyridin-3-ylboronic acid (348 mg, 2.83 mmol, 1.5 eq) and Pd(PPh3)4 (20 mg, 0.02 mmol, 0.01 eq) dissolved in DCM (1.9 mL) and DMF (4.2 mL). The flask was put under an argon atmosphere and aqueous K2CO3 (2 M, 2.36 mL, 4.73 mmol, 2.5 eq) was added. The reaction mixture was stirred at 85°C for 2.5 h, filtered over Celite and concentrated under reduced pressure. The residue was purified via flash-column-chromatography (SiO2, 50% to 90% EtOAc in pentane) to yield the product (296 mg, 74%). 1H NMR (400 MHz, chloroform-d) δ 8.83 (d, J = 1.9 Hz, 1H), 8.57 (dd, J = 4.8, 1.3 Hz, 1H), 7.88 (dt, J = 7.9, 1.9 Hz, 1H), 7.51 (d, J = 8.1 Hz, 2H), 7.37 (dd, J = 7.8, 4.9 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 3.72 (t, J = 6.4 Hz, 2H), 2.83 - 2.74 (m, 2H), 2.59 (s, 1H), 1.94 (dt, J = 13.9, 6.4 Hz, 2H). 13C NMR (101 MHz, chloroform-d) δ 148.12, 148.09, 142.25, 136.70, 135.37, 134.49, 129.34, 127.23, 123.75, 62.13, 34.28, 31.85. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With thionyl chloride In N,N-dimethyl-formamide at 0 - 20℃; for 19h; | 1-Bromo-4-(3-chloropropyl)benzene (114) 3-(4-Bromophenyl)propan-1-ol (88) (3.5 g, 15 mmol, 1.0 eq) was dissolved in DMF (30 mL). The solution was cooled to 0°C and thionyl chloride (2.36 mL, 32.54 mmol, 2.2 eq) was added and the resulting mixture stirred for 19 h at RT. The mixture was quenched with H2O (1x100 mL) and washed with H2O (2x100 mL). The phases were separated and the combined aqueous layers were extracted with Et2O (2x100 mL). The combined organic layers were dried over Na2SO4, filtered and the solvent removed under reduced pressure. The resulting residue was purified via flash-column-chromatography (SiO2, 100% pentane) to yield the product (3.75 g, 99%). 1H NMR (300 MHz, chloroform-d) δ 7.46 - 7.37 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 2.74 (t, J = 7.4 Hz, 2H), 2.12 - 1.98 (m, 2H). 13C NMR (75 MHz, chloroform-d) δ 139.74, 131.68, 130.44, 120.04, 44.11, 33.90, 32.24. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With palladium diacetate; sodium carbonate; triphenylphosphine In propan-1-ol; water Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / water; 1,4-dioxane / Reflux; Inert atmosphere 2.1: Dess-Martin periodane / dichloromethane / 20 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / 0 °C / Inert atmosphere 3.2: 0 °C / Inert atmosphere 4.1: palladium on activated charcoal; hydrogen / methanol; dichloromethane / 4 h / 20 °C | ||
Multi-step reaction with 6 steps 1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / water; 1,4-dioxane / Reflux; Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 20 °C 3: tetrahydrofuran / 2 h / 0 - 20 °C 4: triethylamine; dmap / dichloromethane / 3 h / 20 °C / Inert atmosphere 5: bis(1,5-cyclooctadiene)nickel (0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; methyl magnesium iodide / dichloromethane; toluene / 0.75 h / 20 °C / Inert atmosphere 6: palladium on activated charcoal; hydrogen / methanol; dichloromethane / 4 h / 20 °C | ||
Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / water; 1,4-dioxane / Reflux; Inert atmosphere 2.1: Dess-Martin periodane / dichloromethane / 20 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / 0 °C / Inert atmosphere 3.2: 0 °C / Inert atmosphere 4.1: palladium on activated charcoal; hydrogen / methanol; dichloromethane / 4 h / 20 °C 5.1: lithium aluminium tetrahydride / diethyl ether / 2 h / 0 - 20 °C / Inert atmosphere 6.1: triethylamine; dmap / dichloromethane / 3 h / 20 °C / Inert atmosphere 7.1: bis(1,5-cyclooctadiene)nickel (0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl / dichloromethane; toluene / 0.75 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: tetrakis(actonitrile)copper(I) hexafluorophosphate; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 1-methyl-1H-imidazole / acetonitrile / 20 °C 2: tetrahydrofuran / 2 h / 0 - 20 °C 3: tetrahydrofuran / 0 - 20 °C 4: sodium hydroxide; dihydrogen peroxide / tetrahydrofuran; methanol; water / 3 h / 20 °C 5: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / water; 1,4-dioxane / Reflux; Inert atmosphere 6: triethylamine; dmap / dichloromethane / 3 h / 20 °C / Inert atmosphere 7: bis(1,5-cyclooctadiene)nickel (0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; methyl magnesium iodide / dichloromethane; toluene / 8 h / 20 °C / Inert atmosphere; Glovebox | ||
Multi-step reaction with 8 steps 1: tetrakis(actonitrile)copper(I) hexafluorophosphate; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 1-methyl-1H-imidazole / acetonitrile / 20 °C 2: tetrahydrofuran / 2 h / 0 - 20 °C 3: tetrahydrofuran / 0 - 20 °C 4: sodium hydroxide; dihydrogen peroxide / tetrahydrofuran; methanol; water / 3 h / 20 °C 5: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / water; 1,4-dioxane / Reflux; Inert atmosphere 6: triethylamine; dmap / dichloromethane / 3 h / 20 °C / Inert atmosphere 7: bis(1,5-cyclooctadiene)nickel (0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; methyl magnesium iodide / dichloromethane; toluene / 0.08 h / 20 °C / Inert atmosphere; Glovebox 8: bis(1,5-cyclooctadiene)nickel (0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; methyl magnesium iodide / toluene / 0.75 h / 20 °C / Inert atmosphere; Glovebox | ||
Multi-step reaction with 8 steps 1: tetrakis(actonitrile)copper(I) hexafluorophosphate; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 1-methyl-1H-imidazole / acetonitrile / 20 °C 2: tetrahydrofuran / 2 h / 0 - 20 °C 3: tetrahydrofuran / 0 - 20 °C 4: sodium hydroxide; dihydrogen peroxide / tetrahydrofuran; methanol; water / 3 h / 20 °C 5: tetrakis(triphenylphosphine) palladium(0); potassium carbonate / water; 1,4-dioxane / Reflux; Inert atmosphere 6: triethylamine; dmap / dichloromethane / 3 h / 20 °C / Inert atmosphere 7: methyl magnesium iodide / dichloromethane; toluene / 0.75 h / 20 °C / Glovebox; Inert atmosphere 8: bis(1,5-cyclooctadiene)nickel (0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; methyl magnesium iodide / toluene / 0.75 h / 20 °C / Inert atmosphere; Glovebox |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 1,10-Phenanthroline; triethylamine In 1,2-dichloro-ethane at 120℃; for 16h; Autoclave; Sealed tube; | 4.2 General procedures for one-pot tandem hydroformylation-transfer hydrogenation of olefins with CO and FA General procedure: In a typical experiment, [Ir(COD)Cl]2 (0.025mmol), L1 (0.05mmol) (or the other ligand) were mixed with styrene (5mmol, or the other olefin), FA (25mmol), Et3N (0.125mol if required) and DCE (2mL, or the other solvent). The mixture was added in a 50mL sealed Teflon-lined stainless steel autoclave which was purged with CO (0.5MPa) for three times and then pressured by CO to 3.0MPa. Then the reaction mixture was stirred vigorously at appointed temperature for some time. Upon completion, the autoclave was cooled down to room temperature and slowly depressurized. The solution was analyzed by GC to determine the conversions (n-dodecane as internal standard) and the selectivities (normalization method), and the products were further identified by GC-mass spectrometry. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88 %Chromat. | With oxygen; potassium carbonate at 150℃; for 48h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.2% | Stage #1: Triisopropyl borate; 3-(4-bromophenyl)propanol With n-butyllithium In tetrahydrofuran; hexane at -80 - -70℃; for 3h; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; hexane; water for 0.25h; Inert atmosphere; | 2.1 Step 1: Preparation of compound of formula 7 In a 1L reaction flask, add 43g of p-bromophenylpropanol (compound of formula 3) and 48.8g of triisopropyl borate, dissolve it fully with 200mL of tetrahydrofuran, and under the protection of nitrogen, in the temperature range of -70~-80°C inside, 104 mL of 2.5M n-butyl lithium n-hexane solution was added, and the temperature was controlled to react for 3 hours. Add dilute hydrochloric acid to the reaction solution to adjust pH=2-3, stir for 15min, separate the liquids, extract the aqueous phase with 3×100mL ethyl acetate, combine the organic phases, wash the organic phase with saturated brine to pH=7, anhydrous sulfuric acid After drying with sodium, concentrating, beating with 100 mL petroleum ether, filtering with suction, and drying the filter cake, 26 g of white solid (the compound of formula 7, 4-hydroxyphenylboronic acid) was obtained, and the yield was 72.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85.5% | With bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II); sodium hydrogencarbonate In ethanol; water; toluene for 3h; Reflux; Inert atmosphere; | 1.2 In a 2L reaction flask, add 115.3g (4-(difluoro(3,4,5-trifluoromethoxy)methyl)-3,5-difluorophenyl)boronic acid (compound of formula 2), 63.6 g of p-bromophenylpropanol (compound of formula 3) and 75 g of sodium bicarbonate are fully dissolved in a mixed solvent of 1.2 L of toluene, ethanol and water (the volume ratio of toluene, ethanol and water is 2:1:1). Under nitrogen protection, add 0.08g dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium (II) (Pd-132), and react under reflux for 3h. The reaction solution was cooled, 300 mL of water was added to the reaction solution for separation, the aqueous phase was extracted with 3×200 mL of ethyl acetate, the organic phases were combined, the organic phase was washed with saturated brine to pH=7, dried over anhydrous sodium sulfate, and concentrated , Beaten with 300mL petroleum ether, filtered with suction, and dried the filter cake to obtain 112g of white solid (the compound of formula 4, 3-(4'-(difluoro(3,4,5-trifluoromethoxy)methyl)-3',5'-difluoro-[1,1'-biphenyl]-4-yl)propan-1-ol) with a yield of 85.5%, as shown in Figure 2 for its MS chart. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium tetrahydroborate at 20℃; for 24h; | 1.4 (4) Add methyl 4-bromocinnamate (19.6mmol) and sodium borohydride (58.6mmol) into the reaction flask, add 100mL polyethylene glycol 400, and react at room temperature for 24 hours to obtain 4-bromophenylpropanol (15.9 mmol, 81% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 3-(4-bromophenyl)propanol With sodium hydride In diethyl ether; N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 4-Vinylbenzyl chloride In ethanol at 0 - 20℃; for 2h; | 1.5 (5) Add 4-bromophenylpropanol (3.3mmol) and sodium hydride (6.0mmol) dissolved in 10mL ether and 4mL DMF into the reaction flask, react at room temperature for 1 hour, and then lower the reaction temperature to 0°C. Then 4-chloromethylstyrene (2.3 mmol) dissolved in 3 mL of ethanol was added to the mixture.After 5 minutes of reaction, return to room temperature and continue stirring for 2 hours. The reaction was quenched with water, the organic phase was extracted with ethyl acetate, the organic phase was dried with anhydrous sodium sulfate, and the organic phase was concentrated to obtain 1-bromo-4-(3-((4 -Vinylbenzyl)oxy)propyl)benzene (yield: 80%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With 1,2-Diiodoethane; tetraethylammonium iodide; triphenylphosphine In N,N-dimethyl-formamide at 80℃; for 12h; Sealed tube; Glovebox; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; N–phenyl–2–(dicyclohexylphosphino)pyrrole In 1,4-dioxane; 1,2-dimethoxyethane at 100℃; for 24h; Sealed tube; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In methanol; water at 70℃; for 15h; Inert atmosphere; | A mixture of AP2312M-51 (25.0 g, 116 mmoL), 4-Isopropylphenylboronic acid (22.8 g, 139 mmoL), PdCl2(dppf) (878 mg, 1.2 mmoL) and K2CO3 (32.0 g, 232 mmoL) in MeOH (300 mL) and H2O (100 mL) was degassed by vacuum/nitrogen purge three times. After stirring at 70 for 15 h, the reaction mixture was concentrated to remove MeOH and extracted with EtOAc (100 mL X 2). The combined organic layers were concentrated and purified by flash chromatography (PE : EA=10 : 1) to give 22.0 g of AP2312M-52 as off-white solid, 74% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With Rhizomucor miehei lipase; α,α,α-trifluorotoluene In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tert.-butylnitrite; oxygen; 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile at 20℃; for 12h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With tris(4-methoxyphenyl)phosphane In 1,4-dioxane; 1,2-dimethoxyethane; acetonitrile at 40℃; for 24h; Inert atmosphere; Molecular sieve; Sealed tube; Irradiation; chemoselective reaction; |
[ 52221-92-8 ]
3-(2-Bromo-phenyl)-propan-1-ol
Similarity: 0.89
[ 52221-92-8 ]
3-(2-Bromo-phenyl)-propan-1-ol
Similarity: 0.89
[ 52221-92-8 ]
3-(2-Bromo-phenyl)-propan-1-ol
Similarity: 0.89
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 |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
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. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
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: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
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. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
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 |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
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 |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :