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| CAS No. : | 6341-72-6 |
| Formula : | C15H14O2 |
| M.W : | 226.27 |
| SMILES Code : | CC(C1=CC=C(C2=CC=CC=C2)C=C1)C(O)=O |
| English Name : | 2-([1,1'-Biphenyl]-4-yl)propanoic acid |
| MDL No. : | MFCD00156944 |
| InChI Key : | JALUUBQFLPUJMY-UHFFFAOYSA-N |
| Pubchem ID : | 22810 |
* 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 |
|---|---|---|
| 76% | With hydrogenchloride; sodium hydroxide 1.) reflux; | |
| 76% | With hydrogenchloride; sodium hydroxide | |
| With sodium hydroxide Yield given; |
| With sodium hydroxide at 80 - 85℃; for 3h; | ||
| With sodium hydroxide In water Heating; Yield given; | ||
| With hydroxide Yield given; | ||
| With sodium hydroxide | ||
| 3.37 g | With potassium hydroxide In methanol at 20℃; | |
| 1.29 g | Stage #1: Methyl 2-(4'-biphenylyl)propanoate With lithium hydroxide In tetrahydrofuran; methanol; water Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 100% | With oxalyl dichloride; N,N-dimethyl-formamide In chloroform at 0 - 25℃; | |
| With thionyl chloride |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 76.4% | Stage #1: 2-([1,1'-biphenyl]-4-yl)acetic acid With lithium dipropan-2-ylazanide In tetrahydrofuran; hexane at -84℃; for 2h; Stage #2: methyl iodine In tetrahydrofuran; hexane at -84 - 25℃; for 5h; | |
| Stage #1: 2-([1,1'-biphenyl]-4-yl)acetic acid With n-butyllithium In tetrahydrofuran; hexanes at 0℃; for 0.166667h; Inert atmosphere; Stage #2: methyl iodine In tetrahydrofuran; hexanes Inert atmosphere; | ||
| Stage #1: 2-([1,1'-biphenyl]-4-yl)acetic acid With n-butyllithium; N-isopropylpropan-2-amine In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: methyl iodine In tetrahydrofuran at 20℃; Inert atmosphere; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With salcomine; tetrabutylammonium perchlorate In N,N-dimethyl-formamide at 5℃; Electrochemical reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 93% | With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane; water | R.1 REFERENCE EXAMPLE 1 STR47 REFERENCE EXAMPLE 1 STR47 In usual manner, lithium diisopropylamide in tetrahydrofuran was prepared with diisopropylamine (3.2 ml, 22.6 mmol) and 1.6M n-butyllithium in hexane (14.2 ml, 22.6 mmol). ("Reagents for Organic Synthesis", 2, p. 249) To this lithium diisopropylamide in tetrahydrofuran was added dropwise 4-biphenylyl acetic acid (2.40 g, 11.3 mmol) in tetrahydrofuran at from -50° C. to -30° C. After the mixture was reacted at from -40° C. to -10° C. for 2 h, to the mixture was added dropwise methyliodide (1.77 g, 12.4 mmol) in tetrahydrofuran, then the temperature was rised at from -30° C. to room temperature in nature. After the mixture was stirred for 4 h, was added water and was adjusted at pH 2 with 3N sulfonic acid, then extracted with ether. After the ether extract was dried over, then the extract was evaporated under reduced pressure to a residue, which was chromatographed to afford 2-(4-biphenylyl)propionic acid (2.38 g, 93% yield) as white crystalline material: mp 144°-145° C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 80% | With nickel(II) bromide dimethoxyethane; tetrabutylammonium tetrafluoroborate; 4,4'-di-tert-butyl-2,2'-bipyridine In water; N,N-dimethyl-formamide at 20℃; for 10h; Electrochemical reaction; | |
| 62% | Stage #1: carbon dioxide; p-vinylbiphenyl With [NiBr2(2,9-dimethyl-1,10-phenanthroline)]; diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; 4CzIPN; potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; Molecular sieve; Irradiation; Stage #2: With hydrogenchloride; water regioselective reaction; | |
| 40% | Stage #1: p-vinylbiphenyl With N-(2,6-diisopropylphenyl)-N-((1E)-1-(6-[(1E)-N-(2,6-diisopropylphenyl)ethanimidoyl]pyridin-2-yl)ethylidene)amine; ethylmagnesium bromide; iron(II) chloride In tetrahydrofuran; diethyl ether at 20℃; for 2h; Inert atmosphere; Stage #2: carbon dioxide In tetrahydrofuran; diethyl ether for 0.5h; Inert atmosphere; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With triethylamine In acetonitrile at 20℃; for 0.00833333h; Sonication; | 4.2. general procedure for the syntheses of acyl/sulfonly hydrazines General procedure: In a 100 mL round-bottom flask, benzoic acid 1 (0.122 g= 1 mmol) / benzene sulfonic acid 18 (0.152 g = 1 mmol),and triethylamine (0.1 ml = 1.2 mmol) in acetonitrile (10mL) were taken. 1,1-carbonyldiimidazole (0.162 g = 1mmol) was added to the above-mentioned mixture and reflux for 15 to 30 min. Acyl imidazole formation was confirmedby TLC monitoring. Then, hydrazine hydrate 55% (SigmaAldrich) (1 mL) was added into the reaction mixture andfurther reflux for 2-4 h. After completion (TLC monitoring), the reaction mixture was poured onto crushed ice, formed precipitates were filtered and washed with plenty of distilled water and then with hexane. The crude products were recrystallized from ethyl acetate and hexane. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 88% | With palladium diacetate; acetic anhydride; tris(para-trifluoromethyl)phenyl phosphine In toluene at 65℃; for 48h; Inert atmosphere; Sealed tube; regioselective reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 61% | With 2-methyl-propan-1-ol; RuPhos Pd G4; sodium tert-pentoxide In toluene at 80℃; for 18h; Sealed tube; Inert atmosphere; | |
| 61% | With Ruphos Pd G4; sodium tert-pentoxide; isopropyl alcohol In toluene at 80℃; Inert atmosphere; | |
| 60 % | With 18-crown-6 ether; potassium <i>tert</i>-butylate; hydrogen; C39H60ClGaN4P3Rh(1-)*Li(1+)*4C4H8O In tetrahydrofuran at 20 - 25℃; Irradiation; Sealed tube; |
| 78 % | With tetrahydrofuran; 2,2-diphenylacetic acid; sodium formate; Lithium 1,1,1,3,3,3-hexamethyldisilazide at 0℃; Schlenk technique; Inert atmosphere; Irradiation; |

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89% | With 4CzIPN; triisopropylsilanethiol In N,N-dimethyl-formamide at 0℃; for 24h; Irradiation; Sealed tube; | |
| 85% | With N,N-dicyclohexyl-N-ethylamine; 4DPAIPN In dimethyl sulfoxide at 30℃; for 24h; Irradiation; | |
| 77% | With tetrabutylammonium perchlorate; 1,2-dichloro-ethane; sodium iodide at 20℃; for 12h; Electrolysis; Green chemistry; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 87.6% | Stage #1: 4-bromo-1,1'-biphenyl With iodine; magnesium In tetrahydrofuran at 65 - 70℃; for 2h; Stage #2: magnesium 2-bromopropionate With tris(acetylacetonato)cobalt(III); N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -5 - 5℃; for 3h; | 17 Example 2 General procedure: Add 4.8g of magnesium chips, 250ml of THF and catalytic amount of iodine to the 1000ml reaction flask A, heat it up to 65°C, and dropwise add a solution of 46.6g of 4-bromobiphenyl and 100ml of THF. rising phenomenon occurs.Control the temperature at 65-70°C for about 1h to complete the dropwise addition, and then keep the reaction for 1h until the raw material is less than 2% monitored by HPLC, and cool to below 10°C for use.Add 38.5g sodium 2-bromopropionate, 200ml THF, 3.56g Co(acac)3and 1.16g TMEDA to 1000ml reaction flask B, ccool down to -5-0 deg.C in ice-salt bath, add dropwise the Grignard reaction solution, keep the internal temperature at -5 ~ 5 and finish dropping for about 2 hours, and then react for 1 hour to monitor the reaction by HPLC without change.Add about 300ml of 1N HCl solution to quench the reaction and adjust the pH to 3-4, stir for 1h, filter, stand the filtrate for 0.5h, and separate the layers. The lower aqueous phase is extracted twice with 300ml of ethyl acetate, and the organic layers are combined and saturated with 100ml The NaCl solution was washed once and concentrated under reduced pressure until no liquid was distilled.Add 500ml of 50% methanol/water solution to crystallize, filter and dry to obtain deflurbiprofen as a white powder product (41.4g, yield 91.6%, purity 99.3% (HPLC)), |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91.6% | Stage #1: 4-bromo-1,1'-biphenyl With iodine; magnesium In tetrahydrofuran at 65 - 70℃; for 2h; Stage #2: 2-bromopropionic acid sodium salt With tris(acetylacetonato)cobalt(III); N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -5 - 5℃; for 3h; | 2; 10-15 Example 2 Add 4.8g of magnesium chips, 250ml of THF and catalytic amount of iodine to the 1000ml reaction flask A, heat it up to 65°C, and dropwise add a solution of 46.6g of 4-bromobiphenyl and 100ml of THF. rising phenomenon occurs.Control the temperature at 65-70°C for about 1h to complete the dropwise addition, and then keep the reaction for 1h until the raw material is less than 2% monitored by HPLC, and cool to below 10°C for use.Add 38.5g sodium 2-bromopropionate, 200ml THF, 3.56g Co(acac)3and 1.16g TMEDA to 1000ml reaction flask B, cool down to -5-0 deg.C in ice-salt bath, add dropwise the Grignard reaction solution, keep the internal temperature at -5 ~ 5 and finish dropping for about 2 hours, and then react for 1 hour to monitor the reaction by HPLC without change.Add about 300ml of 1N HCl solution to quench the reaction and adjust the pH to 3-4, stir for 1h, filter, stand the filtrate for 0.5h, and separate the layers. The lower aqueous phase is extracted twice with 300ml of ethyl acetate, and the organic layers are combined and saturated with 100ml The NaCl solution was washed once and concentrated under reduced pressure until no liquid was distilled.Add 500ml of 50% methanol/water solution to crystallize, filter and dry to obtain deflurbiprofen as a white powder product (41.4g, yield 91.6%, purity 99.3% (HPLC)), |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 84.4% | Stage #1: 4'-biphenyl chloride With iodine; magnesium In tetrahydrofuran at 65 - 70℃; for 2h; Stage #2: 2-bromopropionic acid sodium salt With tris(acetylacetonato)cobalt(III); N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -5 - 5℃; for 3h; | 20 Example 2 General procedure: Add 4.8g of magnesium chips, 250ml of THF and catalytic amount of iodine to the 1000ml reaction flask A, heat it up to 65°C, and dropwise add a solution of 46.6g of 4-bromobiphenyl and 100ml of THF. rising phenomenon occurs.Control the temperature at 65-70°C for about 1h to complete the dropwise addition, and then keep the reaction for 1h until the raw material is less than 2% monitored by HPLC, and cool to below 10°C for use.Add 38.5g sodium 2-bromopropionate, 200ml THF, 3.56g Co(acac)3and 1.16g TMEDA to 1000ml reaction flask B, cool down to -5-0 deg.C in ice-salt bath, add dropwise the Grignard reaction solution, keep the internal temperature at -5 ~ 5 and finish dropping for about 2 hours, and then react for 1 hour to monitor the reaction by HPLC without change.Add about 300ml of 1N HCl solution to quench the reaction and adjust the pH to 3-4, stir for 1h, filter, stand the filtrate for 0.5h, and separate the layers. The lower aqueous phase is extracted twice with 300ml of ethyl acetate, and the organic layers are combined and saturated with 100ml The NaCl solution was washed once and concentrated under reduced pressure until no liquid was distilled.Add 500ml of 50% methanol/water solution to crystallize, filter and dry to obtain deflurbiprofen as a white powder product (41.4g, yield 91.6%, purity 99.3% (HPLC)), |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 89.7% | Stage #1: 4-phenyliodobenzene With iodine; magnesium In tetrahydrofuran at 65 - 70℃; for 2h; Stage #2: 2-bromopropionic acid sodium salt With tris(acetylacetonato)cobalt(III); N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -5 - 5℃; for 3h; | 21 Example 2 General procedure: Add 4.8g of magnesium chips, 250ml of THF and catalytic amount of iodine to the 1000ml reaction flask A, heat it up to 65°C, and dropwise add a solution of 46.6g of 4-bromobiphenyl and 100ml of THF. rising phenomenon occurs.Control the temperature at 65-70°C for about 1h to complete the dropwise addition, and then keep the reaction for 1h until the raw material is less than 2% monitored by HPLC, and cool to below 10°C for use.Add 38.5g sodium 2-bromopropionate, 200ml THF, 3.56g Co(acac)3and 1.16g TMEDA to 1000ml reaction flask B, cool down to -5-0 deg.C in ice-salt bath, add dropwise the Grignard reaction solution, keep the internal temperature at -5 ~ 5 and finish dropping for about 2 hours, and then react for 1 hour to monitor the reaction by HPLC without change.Add about 300ml of 1N HCl solution to quench the reaction and adjust the pH to 3-4, stir for 1h, filter, stand the filtrate for 0.5h, and separate the layers. The lower aqueous phase is extracted twice with 300ml of ethyl acetate, and the organic layers are combined and saturated with 100ml The NaCl solution was washed once and concentrated under reduced pressure until no liquid was distilled.Add 500ml of 50% methanol/water solution to crystallize, filter and dry to obtain deflurbiprofen as a white powder product (41.4g, yield 91.6%, purity 99.3% (HPLC)), |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 60% | With 2,4,6-trimethyl-pyridine; 1,10-o-phenanthroline; manganese bis(trifluoromethanesulfonate); trimethylsilylazide; tetra-n-butylammonium tetrafluoroborate; cerium trifluoromethanesulfonate In 2,2,2-trifluoroethanol; N,N-dimethyl-formamide; acetonitrile at 20℃; Inert atmosphere; Irradiation; Electrolysis; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 79% | With di-tert-butyl peroxide; water; tetra-(n-butyl)ammonium iodide; Diphenylphosphine oxide; nickel dibromide at 140℃; for 12h; Autoclave; | 25 Example 25: Preparation of 2- (4-biphenyl) propionic acid In the ampoule was added nickel bromide (0.02mg), L3Ligand (1.0mg), tetrabutylammonium iodide (1.9mg), di-tert-butyl peroxide (184μL), 4-ethylbiphenyl (3mL) and water (36μL), the ampoule is placed in the autoclave, the air in the CO displacement kettle is three times and filled with 30atm carbon monoxide, heated to 140 °C for 12 hours. After the autoclave is cooled, the CO in the kettle is slowly released. After the solvent in the ampoule was removed by distillation under reduced pressure, petroleum ether and ethyl acetate were used as the eluent (petroleum ether/ethyl acetate = 2/1-1/2), and the residue was separated by column chromatography to obtain phenylacetic acid products, with a yield of 79% |
| 40 % | With di-tert-butyl peroxide; water; tetra-(n-butyl)ammonium iodide; Diphenylphosphine oxide; nickel dibromide at 140℃; Autoclave; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 86 % | With ammonium tetrachloropalladate; acetic anhydride; DavePhos In 1,2-dichloro-ethane at 60℃; Inert atmosphere; Sealed tube; regioselective reaction; | |
| 86 % | With ammonium tetrachloropalladate(II); acetic anhydride; DavePhos In cis-1,2-Dichloroethylene at 60℃; Inert atmosphere; | 6 The synthesis reaction of carboxylic acid II-f is: (NH4)2PdCl4 (0.0071 g, 0.025 mmol), 2-dicyclohexylphosphin-2'-(N,N-dimethylamine) biphenyl (0.0394 g, 0.1 mmol), oxalic acid (0.135 g, 1.50 mmol), and acetic anhydride (0.1029 g, 1.0 mmol) Add to the reaction vessel, add 0.50mL of the first organic solvent dichloroethane, 4-phenylstyrene I-f (0.0902g, 0.50mmol), fill with Ar, and react at 60 °C for 24h. Column chromatography, the specific conditions are: the column is packed with petroleum ether, the eluent is petroleum ether/ethyl acetate, and II-f white solid (0.0971g, 86% yield) is obtained. |