Structure of 32707-89-4
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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.
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| CAS No. : | 32707-89-4 |
| Formula : | C9H6F6O |
| M.W : | 244.13 |
| SMILES Code : | OCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 |
| MDL No. : | MFCD00009907 |
| InChI Key : | BJTWPJOGDWRYDD-UHFFFAOYSA-N |
| Pubchem ID : | 122933 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
| Num. heavy atoms | 16 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.33 |
| Num. rotatable bonds | 3 |
| Num. H-bond acceptors | 7.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 42.57 |
| TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.14 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.8 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.37 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.6 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.79 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.54 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.2 |
| Solubility | 0.155 mg/ml ; 0.000635 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.88 |
| Solubility | 0.321 mg/ml ; 0.00131 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.01 |
| Solubility | 0.0241 mg/ml ; 0.0000986 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
| BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
| P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.8 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.59 |
* 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 |
|---|---|---|
| 90% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper diacetate; In water; acetonitrile; at 20℃; for 6h;Green chemistry; | General procedure: A mixture of alcohol (5.0 mmol), Cu(OAc)2 (9.1 mg, 0.05 mmol), and TEMPO (7.8 mg, 0.05 mmol) in CH3CN/H2O (5/10 mL) was stirred at room temperature for specified time. After completion of the reaction (monitored by TLC, eluents: petroleum ether/ethyl acetate = 4/1), dichloromethane (10 mL) was added to the resulting mixture. The dichloromethane phase was separated, and the aqueous phase was further extracted with dichloromethane (10 mL × 2). The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give a residue, which was purified by column chromatography (eluents: petroleum ether/ethyl acetate = 10/1) to provide the desired product. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 74% | With lithium aluminium tetrahydride; In diethyl ether; at 0 - 35℃; for 10h; | Into 460 ml (0.46 mol) of a 1.0 M diethyl ether solution of aluminum lithium hydride cooled to 0C, 80 g (0.31 mol) of 3,5-bis(trifluoromethyl)benzoic acid obtained in the same manner as in Example 2 was gradually added. The reaction solution was heated to the reflux temperature (35C) while stirring under a nitrogen flow to continue the reaction for 10 h. After completion of the reaction, the reaction solution was cooled to 0C and 20 ml of water was added over 15 min. Then, 20 ml of a 15% sodium hydroxide aqueous solution and 60 ml of water were gradually added. After stirring for 30 min, the organic phase was separated by filtration and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the organic phase was analyzed by gas chromatography. It was confirmed that 58.6 g (0.24 mol) of the aimed 3,5-bis(trifluoromethyl)benzyl alcohol was produced (yield: 78%; selectivity: 91%). By vacuum distillation after removing ether, 55.9 g (0.23 mol) of 3,5-bis(trifluoromethyl)benzyl alcohol was isolated (yield: 74%). The purity determined by gas chromatography was 99% or higher. The results of ICP total elements analysis showed that none of Li, Na, K, Mg, Ca, Sr, Ba, Sc, Y, Ti, Zr, V, Nb, Cr, Mo, W, Mn, Fe, Ru, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, Al, In, Si, Sn, Pb, P, Sb and S were detected, and the content of each of group 1 and group 2 elements was 1 ppm or lower. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Purification / work up; | EXAMPLES 17 to 31 In the same manner as in Examples 2 to 16, each (fluoroalkyl)benzene derivative was produced. To reduce the impurities, the crystallization was conducted twice in Example 17 and the final distillation was repeated in the other examples. The purity, residual halogen content and residual metal content of the (fluoroalkyl)benzene derivatives are collectively shown in Table 2 |
[ 401-95-6 ]
[ 557-20-0 ]
[ 32707-89-4 ]

[ 6066-82-6 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 32707-89-4 ]
[ 1122-58-3 ]
[ 32707-89-4 ]
[ 538-75-0 ]
[ 2243-42-7 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 32% | In dichloromethane; at 0 - 20℃; | EXAMPLE 13 2-Phenoxy-benzoic acid 3,5-bis-trifluoromethyl-benzyl ester To a solution of 118 mg (0.55 mmol) 2-phenoxybenzoic acid and 122 mg (0.50 mmol) 3,5 bis(trifluoromethyl)benzyl alcohol in 1.5 ml dichloromethane at 0 C. was added a solution of 124 mg (0.60 mmol) 1,3-dicyclohexylcarbodiimide and 7 mg (0.06 mmol) 4-dimethylaminopyridine in 1 ml dichloromethane.. The ice bath was removed and stirring was continued at room temperature overnight.. The solvent was removed in vacuo and the residue re-dissolved in diethyl ether, filtered and evaporated.. The residue was purified by flash chromatography to give 70 mg (32%) of the title compound as white crystals. MS m/e (%): 440 (M+, 51), 347 (39), 227 (36), 197 (100). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 82.5% | With hydrogen;aluminum nickel; In toluene; | Example 5 (not according to the invention) 37 g of 3,5-bis(trifluoromethyl)benzaldehyde and 4 g of Raney nickel together with 150 ml of toluene were placed in a reaction vessel at room temperature. The vessel was pressurized with 30 bar of hydrogen gas and the mixture was hydrogenated at 50 C. for 7.5 hours while stirring. The mixture was subsequently cooled to room temperature, depressurized and the catalyst was filtered off. The filtrate was evaporated and the crude product obtained in this way was distilled at 17 mbar. 3,5-bis(trifluoromethyl)benzyl alcohol having a boiling point of 97 C. was obtained in a yield of 31.5 g and a purity of 97.7%. This corresponds to a yield of 82.5% of theory. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 99.1% | With sulfuric acid; hydrogen bromide; In water; at 50 - 105℃; for 10h;Heating / reflux; | EXAMPLE 2 Preparation of 3, 5-bis (trifluoromethyl)-benzyl bromide; In a 4-neck flask with capacity 1000 ml equipped with mechanical agitator, thermometer, bubble condenser and 100 ml loading funnel, 262.2 g of the product of Example 1 (ii) at 92. 8% (0. 988 moles), 550,2 g HBr 48% (3.2645 moles) are loaded; this is heated at 50C so as to melt the alcohol, then one starts to dose 113 g of concentrated His04 (1.153 moles). Pouring is accomplished in 30 minutes, noting an increase of the internal temperature. This is heated to 100-105C and left to react for 8 hours. The reaction is completed by reflux heating for per 1.5 hours. the mixture is left to settle and the phases are separated; the solvents are removed from the organic phase and the product in the title is obtained with a yield of 99.1 %. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| > 92% | (ii)-Preparation of 3, 5-bis (trifluoromethvl)-benzylalcohol; 53.8 g of solid paraformaldehyde (1,7933 moles) are added to the reaction mixture obtained in the previous step (i), dosing it in two portions of about 27g. The reaction is exothermic. It is left to react at 45C for 6 hours and then the organo-magnesium adduct is hydrolysed with 1002.3 g of H2S04 at 20%, cooling the system by means of an ice/water bath (Tm, 337C), after which it is kept stirring vigorously for another hour. the mixture is left to settle, the two phases are separated and the solvents are eliminated from the organic phase; it is then distilled in a vacuum (20 mbar) collecting 318.6 g of evaporated crude alcohol (tit. > 92%). |

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