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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4'-Trifluoromethyl-2-biphenyl carboxylic acid (Xenalipin) is a biphenyl carboxylic acid derivative with lipid-lowering activity. It reduces blood cholesterol and triglycerides in rats and is considered an orally active hypolipidemic agent.
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CAS No. : | 84392-17-6 |
Formula : | C14H9F3O2 |
M.W : | 266.22 |
SMILES Code : | OC(=O)C1=C(C=CC=C1)C1=CC=C(C=C1)C(F)(F)F |
MDL No. : | MFCD00075353 |
InChI Key : | IQOMYCGTGFGDFN-UHFFFAOYSA-N |
Pubchem ID : | 55251 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With water; lithium hydroxide; In tetrahydrofuran; methanol; at 60.0℃; | To a solution of methyl 4’-(trifluoromethyl)[1,T-biphenyl]-2-carboxylate (120 mg, 428 μmol) in THF (1 .5 ml) and methanol (300 pi) was added an aqueous lithium hydroxide solution (1 .1 ml, 2.0 M, 2.1 mmol) and the mixture was stirred at 60 Cfor 5 hours. An aqueous solution of lithium hydroxide (1 .1 ml, 2.0 M, 2.1 mmol) was added and the reaction was stirred at 60 C over night. The mixture was acidified with excess 2N aqueous hydrochloric acid and was extracted with ethyl acetate and the organic layers were dried, filtered and evaporated. Purification was done by flash chromatography (n-heptane- n-heptane : ethyl acetate (50:50)). Product containing samples were united, the solvents were evaporated. 97.0 mg (99 % purity, 84 % yleld) of the title compound were obtained. LC-MS (Method 7): Rt = 1 .87 min; MS (ESIneg): m/z = 265 [M-H]- 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.006 (0.47), 1 .234 (0.49), 2.731 (0.57), 2.890 (0.71), 7.408 (7.62), 7.410 (7.81 ), 7.423 (8.91 ), 7.425 (8.64), 7.514 (4.14), 7.516 (4.14), 7.529 (11.51), 7.532 (14.91 ), 7.535 (14.57), 7.545 (8.62), 7.547 (11.70), 7.551 (15.41 ), 7.614 (5.63), 7.617 (5.78), 7.630 (8.61), 7.632 (8.40), 7.645 (3.72), 7.647 (3.45), 7.762 (16.00), 7.778 (13.68), 7.819 (8.50), 7.822 (8.25), 7.835 (7.76), 7.837 (7.12), 12.881 (1 .65). |
With potassium hydroxide; In methanol; at 80.0℃; | General procedure: To a 50 mL oven-dried Schlenk flask equipped with a magnetic stir bar, were added methyl 2-iodobenzoate (2.62 g, 10 mmol), arylboronic acid (15 mmol),Pd(OAc)2 (22 mg, 1 mol%), PPh3 (52 mg, 2 mol%) and K3PO4 (4.24 g, 20 mmol).The Schlenk flask was evacuated and backfilled with N2 for 3 times. Then toluene (20mL) was added. The reaction mixture was heated at 80 C. The reaction progress wasmonitored by thin-layer chromatography (TLC) analysis. After the reaction was completed, the mixture was cooled to room temperature. Then the reaction mixture was concentrated on a rotary evaporator, and purified by column chromatography(PE/EtOAc = 50/1) to give the desired ester.KOH (3.0 g, 75 mmol), MeOH (20 mL) and the desired ester were added to a50-mL of flask, and the mixture was heated at 80 oC for 2-12 h (TLC monitored). The reaction mixture was cooled to room temperature. Then the reaction mixture was acidified and extracted with DCM (3 x 30 mL). Combined organic extract was dried with Na2SO4, concentrated on a rotary evaporator and the residue was purified bycolumn chromatography on silica gel using PE/EtOAc = 5/1 as eluent to afford theproduct. To a 50 mL oven-dried Schlenk flask equipped with a magnetic stir bar, were added methyl 2-iodobenzoate (10 mmol), phenylboronic acid (15 mmol), Pd(OAc)2(112 mg, 5 mol%), DPPF (338 mg, 6 mol%) and K3PO4 (20 mmol). The Schlenk flask was evacuated and backfilled with N2 for 3 times. Then 1,2-dimethoxyethane (30 mL)was added. The reaction mixture was heated at 80 C. The reaction progress was monitored by thin-layer chromatography (TLC) analysis. After the reaction was completed, the mixture was cooled to room temperature. Then the reaction mixture was concentrated on a rotary evaporator, and purified by column chromatography(PE/EtOAc = 50/1) to give the desired ester.KOH (3.0 g, 75 mmol), MeOH (20 mL) and the desired ester were added to a 50-mL of flask, and the mixture was heated at 80 oC for 2-12 h (TLC monitored). The reaction mixture was cooled to room temperature. Then the reaction mixture was acidified and extracted with DCM (3 x 30 mL). Combined organic extract was dried with Na2SO4, concentrated on a rotary evaporator and the residue was purified by column chromatography on silica gel using PE/EtOAc = 5/1 as eluent to afford theproduct.Other reagents and solvents were purchased from commercial supplier and used without any further treatment. | |
With water; sodium hydroxide; In methanol; at 50.0℃;Inert atmosphere; | General procedure: Based on a modified literature procedure,24 a round bottom flask was charged with methyl 2-iodobenzoate (2.6 g, 10mmol), arylboronic acid (10.5mmol), PdCl2(PPh3)2 (0.18 g, 0.25mmol), Na2CO3 (2.1 g, 20mmol) in THF (25 mL) and H2O (25 mL) under nitrogen atmosphere. The mixture was stirred at 80 C overnight. The resulting reaction mixture was cooled to room temperature before H2O was added, and the mixture was extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, and the filtrate was evaporated under reduced pressure. The crude material was purified by column chromatography on silica gel (hexane/EtOAc) to afford the corresponding methyl 2-arylbenzoate as a colorless liquid. Next, to a solution of the methyl 2-arylbenzoate (8mmol) in MeOH (32 mL), 1M NaOH in H2O (32 mL) was added slowly. The resultant mixture was stirred at 50 C overnight. The resulting reaction mixture was then acidified using an aqueous solution of HCl (1 M) and extracted with CH2Cl2. The combined organic layer was dried over anhydrous Na2SO4, and the filtrate was evaporated under reduced pressure. The crude material was purified by recrystallization from hexane/EtOAc to afford the desired 2-arylbenzoic acid as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Preparation 91 Methyl 4-[4-([4'-(trifluoromethyl)-1,1'-biphenyl-2-yl]carbonyl}amino)phenyl]butanoate was obtained from 4'-(trifluoromethyl)-1,1'-biphenyl-2-carboxylic acid and <strong>[20637-09-6]methyl 4-(4-aminophenyl)butanoate</strong> in the same manner as in Preparation 1. 1H-NMR (DMSO-d6): delta1.71-1.86 (2H, m), 2.28 (2H, t, J=7.40 Hz), 2.49-2.56 (2H, m), 3.57 (3H, s), 7.09 (2H, d, J=8.36 Hz), 7.45 (2H, d, J=8.36 Hz), 7.47-7.66 (6H, m), 7.75 (2H, d, J=8.38 Hz), 10.30 (1H, s) |
Tags: 4'-Trifluoromethyl-2-biphenyl carboxylic acid | Benzene Compounds | Trifluoromethyls | Fluorinated Building Blocks | Carboxylic Acids | Aryls | Organic Building Blocks | 84392-17-6
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