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CAS No. : | 209991-62-8 | MDL No. : | MFCD00083532 |
Formula : | C8H5F3O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PQGPUBAARWWOOP-UHFFFAOYSA-N |
M.W : | 190.12 | Pubchem ID : | 2777952 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H312-H315-H319-H332-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 |
---|---|---|
With thionyl chloride; In dichloromethane; for 4h;Reflux; | General procedure: SOCl2 (1.65 mL) was added to a solution of benzoic or phenylaceticacid derivatives (2 mmol) in dry CH2Cl2 (1.65 mL), and thesuspension was refluxed for 4 h. The resulting solution was evaporated,the residue was dissolved in dry acetone (10 mL) and 3-(4-aminophenyl)-7-hydroxy-coumarin 4 (0.51 g, 2 mmol) was added.The mixture was refluxed with anhydrous K2CO3 (1.104 g, 8 mmol)for 4 h. Acetone was removed under reduced pressure and coldwater (20 mL) was added. 3 N HCl was added until the solutionbecame acidic. The resulting precipitate was filtered, washed withwater and recrystallized from methanol or ethanol to give thedesired products 5a-k. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
An emulsion of 0.06mol, 13.1g ethyl 3,4,5-trifluorophenylacetate and 100ml 1.35M aqueous NaOH solution (5.4g, 0.135mol, 2eq) is refluxed for 3h. 4 equivalents HCl (diluted aqueous solution) are added after cooling to room temperature. The white precipitate of 3,4,5-trifluorophenylacetic acid (8.7g) is filtered off and recrystallized from hexane (7.7g) (melting point: 100C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLES 107, 108, 109 AND 110; Synthesis of (6R,8S)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(3,4,5-trifluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-6-ol, (6S,8R)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(3,4,5-trifluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-6-ol, (6S,8S)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(3,4,5-trifluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-6-ol and (6R,8R)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(3,4,5-trifluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-6-ol Synthesis of 2-(3,4,5-trifluorophenyl)-4-pentenoic acidn-Butyl lithium (7.89 mL; 2.66 M solution in hexane) was added to a solution of <strong>[209991-62-8]3,4,5-trifluorophenylacetic acid</strong> (2 g) in THF (50 mL) at -78 C. The reaction solution was stirred at -78 C. for 20 minutes. Then, the reaction solution was heated to 0 C. and further stirred for 30 minutes. Allyl bromide (0.999 mL) was added dropwise to the reaction solution, and the reaction solution was stirred at room temperature for three hours. A 1 N sodium hydroxide solution and diethyl ether were added to the reaction solution, and the aqueous layer was separated. 5 N hydrochloric acid and ethyl acetate were added to the resulting aqueous layer, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 1.45 g of the title compound. The property values of the compound are as follows.1H-NMR (CDCl3) δ (ppm): 2.44-2.52 (m, 1H), 2.72-2.81 (m, 1H), 3.58 (t, J=7.6 Hz, 1H), 5.03-5.10 (m, 2H), 5.60-5.71 (m, 1H), 6.90 (dd, J=8.4, 6.4 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; triethylamine; In dichloromethane; at 0℃; for 0.583333h; | EXAMPLES 103 AND 104; Synthesis of (7S,8S)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(3,4,5-trifluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-7-ol and (7R,8R)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(3,4,5-trifluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-7-ol Synthesis of benzyl (3,4,5-trifluorophenyl)acetateTriethylamine (0.808 mL) and benzyl chloroformate (0.752 mL) were sequentially added dropwise to a solution of <strong>[209991-62-8]3,4,5-trifluorophenylacetic acid</strong> (1 g) in methylene chloride (15 mL) at 0 C., and the reaction solution was stirred at 0 C. for five minutes. DMAP (64.4 mg) was added to the reaction solution which was then stirred at 0 C. for 30 minutes. Ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 1.43 g of the title compound. The property values of the compound are as follows.1H-NMR (CDCl3) δ (ppm): 3.59 (s, 2H), 5.14 (s, 2H), 6.90 (dd, J=8.0, 6.4 Hz, 2H), 7.29-7.38 (m, 5H), 3.83 (s, 3H), 3.89 (s, 3H), 6.44 (s, 1H), 6.95 (brs, 1H), 7.04 (d, J=1.6 Hz, 1H), 7.07 (dd, J=8.0, 1.6 Hz, 1H), 7.20 (t, J=8.8 Hz, 2H), 7.28 (d, J=8.0 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.83 (s, 1H), 8.09 (dd, J=8.8, 5.2 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis of 1-amino-3-(3,4,5-trifluorophenyl)piperidin-2-one 6.6 g of the title compound was obtained from <strong>[209991-62-8]3,4,5-trifluorophenylacetic acid</strong> (11 g) according to the method in Examples 20 and 21. The property value of the compound is as follows. ESI-MS; m/z 245 [M++H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; ethyl acetate; | Synthesis of 4-chloro-2-(3,4,5-trifluorophenyl)butyric acid A 2.66 M solution of butyl lithium in hexane (20 mL) was added to a solution of <strong>[209991-62-8]3,4,5-trifluorophenylacetic acid</strong> (5.00 g) in THF (150 mL) in a nitrogen atmosphere at -78C, and the reaction solution was stirred at -78C for 20 minutes. The reaction solution was further stirred at 0C for one hour. Then, 1-bromo-2-chloroethane (2.2 mL) was added at 0C, and the reaction solution was stirred at room temperature for 14 hours. Ethyl acetate and 1 N hydrochloric acid were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 4.54 g of the title compound. The property values of the compound are as follows. 1H-NMR (CDCl3) δ (ppm): 2.13-2.22 (m, 1H), 2.45-2.54 (m, 1H), 3.36 (ddd, J=11.6, 8.4, 4.8Hz, 1H), 3.58 (ddd, J=11.6, 6.4, 5.2Hz, 1H), 3.89 (dd, J=7.6, 7.6Hz, 1H), 6.94-7.02 (m, 2H). | |
A 2.66 M solution of butyl lithium in hexane (20 mL) was added to a solution of <strong>[209991-62-8]3,4,5-trifluorophenylacetic acid</strong> (5.00 g) in THF (150 mL) in a nitrogen atmosphere at -78 C., and the reaction solution was stirred at -78 C. for 20 minutes. The reaction solution was further stirred at 0 C. for one hour. Then, 1-bromo-2-chloroethane (2.2 mL) was added at 0 C., and the reaction solution was stirred at room temperature for 14 hours. Ethyl acetate and 1 N hydrochloric acid were added to the reaction solution, and the organic layer was separated. The resulting organic layer washed with a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to obtain 4.54 g of the title compound. The property values of the compound are as follows. 1H-NMR (CDCl3) δ (ppm): 2.13-2.22 (m, 1H), 2.45-2.54 (m, 1H), 3.36 (ddd, J=11.6, 8.4, 4.8 Hz, 1H), 3.58 (ddd, J=11.6, 6.4, 5.2 Hz, 1H), 3.89 (dd, J=7.6, 7.6 Hz, 1H), 6.94-7.02 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | To a solution of (3,4,5-trifluorophenyl)acetic acid (561 mg, 2.95 mmol) in THF (12 mL) was added dropwise n-butyllithium 1.6 M hexane solution (3.69 mL, 5.90 mmol) at - 78C, and the mixture was stirred under ice-cooling for 1 hr. 1-Bromo-3-chloropropane (0.305 mL, 3.10 mmol) was added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was extracted with 1 M aqueous sodium hydroxide solution. The extract was acidified with 3 M hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80 - 50/50) to give the title compound as a colorless oil (0.535 g, 68%). 1H NMR (CDCl3) δ: 1.60 - 2.01 (3 H, m), 2.11 - 2.27 (1 H, m), 3.41 - 3.62 (3 H, m), 6.86 - 7.06 (2 H, m). |
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