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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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Batch number can be found on the product's label following the word 'Batch'.
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 35480-52-5 |
Formula : | C11H8F6O4 |
M.W : | 318.17 |
SMILES Code : | OC(=O)C1=C(OCC(F)(F)F)C=CC(OCC(F)(F)F)=C1 |
MDL No. : | MFCD00221424 |
InChI Key : | YPGYLCZBZKRYQJ-UHFFFAOYSA-N |
Pubchem ID : | 2736078 |
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 |
---|---|---|
75.3% | Stage #1: With sodium t-butanolate In DMF (N,N-dimethyl-formamide) at 0 - 25℃; for 1 h; Stage #2: at 100℃; for 10 h; |
To a solution of 2,2,2-trifluoroethanol (14.7 g) and DMF (125 ml) was added sodium tert-butoxide (12.8 g) at 0° C. The solution was stirred at 20 to 25° C. for 1 hour at which point 5-bromo-2-(2,2,2-trifluoroethoxy)benzoic acid (20 g) was added followed by cupric bromide (2.0 g). The mixture was stirred at 100° C. for 10 hours, cooled to 10° C., and water (30 ml) was added followed by 20percent HCl solution (90 ml). The solution was extracted with dichloromethane (3*80 ml), and the combined organic layers were washed with water (3*60 ml). The solution was concentrated to one-third of the original volume and hexane (200 ml) was added. The resulting suspension was stirred at room temperature for 2 hours, filtered and the damp cake was rinsed with hexane (2*40 ml). The damp cake was dried in vacuo at 40° C. for 5 hours to give the product as a white solid (16.02 g, yield 75.3percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With potassium <i>tert</i>-butylate In tetrahydrofuran; water | EXAMPLE 1 300 ml of THF are initially introduced at room temperature, and 84.7 g of potassium tert-butoxide are added with stirring 76.0 g of 2,2,2-trifluoroethanol are added dropwise to this reaction mixture, with the temperature being kept below 35° C. When the addition is complete, stirring is continued, and 29.6 g of 5-bromo-2-chlorobenzoic acid are subsequently introduced. After the subsequent addition of 27.3 g of copper(I) bromide, the reaction mixture is heated to reflux. After 43 hours, the reaction mixture is cooled to 5° C. and allowed to run into dilute hydrochloric acid at 5° C. The organic phase is separated from the aqueous phase,. and the solvent is distilled off, during which the product precipitates. 100 ml of water are added to the residue and then filtered. For purification, the crude product is taken up in MTB ether (methyl tert-butyl ether). Undissolved components are separated off by filtration through neutral aluminium oxide, and the solvent is subsequently removed. Recrystallisation from an ethanol/water mixture gives 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid in a yield of 45percent. Melting point: 120-122° C., purity>98percent (HPLC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.6% | Stage #1: With pyridine; sodium hydroxide In water at 18 - 81℃; for 1 h; Stage #2: With sodium permanganate In water at 81 - 93℃; for 7.75 h; Stage #3: With hydrogenchloride In water |
Example 2 Preparation of 2,5-bis(2,2,2-trifluorethoxy)benzoic acid (III) The 2,5-bis(2,2,2-trifluoroethoxy)toluene (II) (220 g, 0.986 mol) was added to magnetically stirred pyridine (1550 mL) at 18-23°C. The reaction mixture was stirred under a reflux. Thereafter a 10 percent aqueous NaOH solution (20 mL, 0.050 mol) and copper (II) sulphate (0.27 g, 0.0017 mol) were added to the reaction mixture. The reaction mixture was heated at 81 °C for 1 hour at which point a 40percent aqueous sodium permanganate solution (2290 g, 6.45 mol) was added in portions within a time period of 6.5 hours. After the addition of an aqueous sodium permanganate solution the reaction mixture was stirred at 83 to 93°C for 75 minutes. A precipitate of manganese oxides was separated by filtration at 80-95°C, the manganese oxides was rinsed on the filter with 5 liters of hot (80°C) water. The combined filtrates were cooled to 9°C in 50 minutes. The crystallization suspension was filtered to obtain damp cake of unreacted 2,5-bis(2,2,2-trifluoroethoxy)toluene (II), which was removed thereafter. The filtrate of reaction mixture was mixed with activated charcoal (20.0 g) and stirred for 75 minutes; the precipitate of charcoal was separated by filtration and liquid phase was acidified to pH=1-2 using concentrated HCl. The crystallization solution was filtrated and the product cake on the filter was rinsed with 200 mL of water. The intermediate 2,5-bis(2,2,2-trifluorethoxy)benzoic acid (III) was dried at reduced pressure for 18 hours. The 2,5-bis(2,2,2-trifluorethoxy)benzoic acid was obtained as an off-white powder (210.2 g, 81.6percent) having a melting point of 121°C to 125°C. |
75.2% | Stage #1: With pyridine; sodium hydroxide; potassium permanganate In water at 85 - 100℃; for 1 h; Stage #2: With hydrogenchloride In water |
Example 3 Pyridine (310 mL), water (175 mL) and 2,5-bis(2,2,2-trifluoroethoxy)toluene (44.4 g, 0.154 mol) were mixed in a 1 liter round bottom flask, the pH was adjusted to 11-12 with sodium hydroxide. The mixture was heated to 85°C and treated with potassium permanganate in 6 portions of 34 grams each, for a total of 204 g (1.29 mol). The permanganate addition rate was such as to maintain the temperature at 90-100°C. The reaction mixture was maintained at 85-95°C for an additional hour and filtered while hot. The manganese oxide precipitate was washed with water and the washings were combined with the pyridine-water filtrate, then cooled to 5-10°C and filtered to remove the unreacted starting material. The product was isolated by acidifying the filtrate with concentrated hydrochloric acid to pH=1-2 and removing the white precipitate by filtration. After washing on the filter with water and drying under reduced pressure 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid was obtained as white powder in 37.2 g (0.116 mol, 75.2percent) yield having a melting point of 121°C to 125°C. |
Tags: Flecainide Impurity D | Trifluoromethyls | Fluorinated Building Blocks | Carboxylic Acids | Aryls | Ethers | Organic Building Blocks | 35480-52-5
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Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
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Code | Phrase |
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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. |
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P251 | Pressurized container: Do not pierce or burn, even after use. |
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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. |
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P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
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P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
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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 |
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