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CAS No. : | 1530-45-6 | MDL No. : | MFCD00011835 |
Formula : | C22H22BrO2P | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VJVZPTPOYCJFNI-UHFFFAOYSA-M |
M.W : | 429.29 | Pubchem ID : | 73731 |
Synonyms : |
|
Num. heavy atoms : | 26 |
Num. arom. heavy atoms : | 18 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 7 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 115.65 |
TPSA : | 39.89 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | Yes |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.74 cm/s |
Log Po/w (iLOGP) : | -1.48 |
Log Po/w (XLOGP3) : | 5.88 |
Log Po/w (WLOGP) : | 0.55 |
Log Po/w (MLOGP) : | 5.13 |
Log Po/w (SILICOS-IT) : | 4.92 |
Consensus Log Po/w : | 3.0 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -6.26 |
Solubility : | 0.000238 mg/ml ; 0.000000554 mol/l |
Class : | Poorly soluble |
Log S (Ali) : | -6.49 |
Solubility : | 0.000139 mg/ml ; 0.000000323 mol/l |
Class : | Poorly soluble |
Log S (SILICOS-IT) : | -8.39 |
Solubility : | 0.00000174 mg/ml ; 0.0000000041 mol/l |
Class : | Poorly soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 4.73 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-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 water; potassium bromide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | Step 1: Ethyl 4,4,5,5,5-pentafluoro-3-oxo-2-(triphenyl-[5]-phosphanylidene)pentanoate Into a 250-mL 3-necked round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed (2-ethoxy-2-oxoethyl)triphenylphosphanium bromide (17.16 g, 39.97 mmol, 1.00 equiv), tetrahydrofuran (100 mL). The solution was cooled to 0 C. in the ice/water bath. Triethylamine (8.888 g, 87.83 mmol, 2.20 equiv) was added dropwise and stirred at this temperature, stirred for 15 min. Then pentafluoropropanoyl 2,2,3,3,3-pentafluoropropanoate (13.64 g, 43.99 mmol, 1.10 equiv) was added dropwise and stirred for another 2 h. The solids were collected by filtration, washed by the cool THF, collected the organic phase and concentrated. 100 mL distilled water was added to the residue, and stirred violently. The white solid appeared. Filtered and dried under the vacuum. This resulted in 14.4 g (73%) of ethyl 4,4,5,5,5-pentafluoro-3-oxo-2-(triphenyl-[5]-phosphanylidene) pentanoate as a white solid. Mass spectrum (ESI, m/z): Calcd. for C25H20F5O3P, 495.4 (M+H). found 495.4. | |
73% | Into a 250-mL 3-necked round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed (2-ethoxy-2-oxoethyl)triphenylphosphanium bromide (17.16 g, 39.97 mmol, 1.00 equiv), tetrahydrofuran (100 mL). The solution was cooled to 0 C. in the ice/water bath. Triethylamine (8.888 g, 87.83 mmol, 2.20 equiv) was added dropwise and stirred at this temperature, stirred for 15 min. Then pentafluoropropanoyl 2,2,3,3,3-pentafluoropropanoate (13.64 g, 43.99 mmol, 1.10 equiv) was added dropwise and stirred for another 2 h. The solids were collected by filtration, washed by the cool THF, collected the organic phase and concentrated. 100 mL distilled water was added to the residue, and stirred violently. The white solid appeared. Filtered and dried under the vacuum. This resulted in 14.4 g (73%) of ethyl 4,4,5,5,5-pentafluoro-3-oxo-2-(triphenyl-[5]-phosphanylidene)pentanoate as a white solid. Mass spectrum (ESI, m/z): Calcd. for C25H20F5O3P, 495.4 (M+H). found 495.4. | |
73% | Into a 250-mL 3-necked round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed (2-ethoxy-2- oxoethyl)triphenylphosphanium bromide (17.16 g, 39.97 mmol, 1.00 equiv), tetrahydrofuran (100 mL). The solution was cooled to 0C in the ice/water bath. Triethylamine (8.888 g, 87.83 mmol, 2.20 equiv) was added dropwise and stirred at this temperature, stirred for 15 min. Then pentafluoropropanoyl 2,2,3,3,3- pentafluoropropanoate (13.64 g, 43.99 mmol, 1.10 equiv) was added dropwise and stirred for another 2h. The solids were collected by filtration, washed by the cool THF, collected the organic phase and concentrated. 100 mL distilled water was added to the residue, and stirred violently. The white solid appeared. Filtered and dried under the vacuum. This resulted in 14.4 g (73%) of ethyl 4,4,5,5,5-pentafluoro-3-oxo-2- (triphenyl-[5]-phosphanylidene) pentanoate as a white solid. Mass spectrum (ESI, m/z): Calcd. for 495.4 (M+H), found 495.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.8% | In toluene; at 100℃; for 1h; | To a solution of triphenylphosphine (39.04 gm, 0.149 moles) in toluene (700 ml), a solution of ethyl-2-bromo acetate (25 g, 0.149 moles, 1 eq in 300 ml toluene) was added and heated at 100 0C for 1 hr. The reaction mixture was then cooled to room temperature and the precipitated Wittig salt was filtered, washed with hexane and dried under high vacuum to give 60 gm of 1 (93.8% yield) as a white solid. |
92.6% | In ethyl acetate; at 13 - 18℃; for 22h; | Triphenyl phosphine (235.6 g, 0.90 mol) was dissolved in EtOAc (540 mL). Approximately 30 min was required for all of the solids to dissolve. The process was endothermic (solution cooled to 13 C. when the ambient temperature was 20 C.). A solution of ethyl bromoacetate (100 mL, 0.90 mol) in EtOAc (400 mL) was added dropwise over a 1.5 h period. A white precipitate formed during the addition. Stirred overnight (20 h) at ambient temperature (18 C.). The solids were collected by vacuum filtration rinsing with copious amounts of Et2O. Dried overnight in vacuo at 45 C. to give 3 as a white solid 356.3 g, 92.6% yield (0.83 mol). 1H NMR was consistent with literature values. The solid was dissolved in methylene chloride (3 L) and treated with 1 M NaOH (3.6 L) in a 12 L flask with vigorous stirring for 45 min. The organic layer was separated and the aqueous phase was extracted with additional methylene chloride (2*1 L). Organic layers were dried (MgSO4) and concentrated until approximately 1 L of volume remained. A small amount of material was removed and examined by 1H NMR and found to be consistent with literature values |
92.6% | In ethyl acetate; at 18℃; for 21.5h; | [(ETHOXYCARBONYL) METHYLENE] TRIPHENYLPHOSPHORANE (4) 2 (ACL-G29-1) Triphenyl phosphine (235.6 g, 0.90 mol) was dissolved in EtOAc (540 mL). Approximately 30 min was required for all of the solids to dissolve. The process was endothermic (solution cooled to 13 C when the ambient temperature was 20 C). A solution of ethyl bromoacetate (100 mL, 0.90 mol) in EtOAc (400 mL) was added dropwise over a 1.5 h period. A white precipitate formed during the addition. Stirred overnight (20 h) at ambient temperature (18 C). The solids were collected by vacuum filtration rinsing with copious amounts OF ET20. Dried overnight in vacuo at 45 C to give 3 as a white solid 356.3 G, 92.6% yield (0.83 MOL). H NMR was consistent with literature values. |
92% | In ethyl acetate; at 20℃; for 24h;Large scale; | Ethyl acetate (5.0 L) was added to triphenylphosphine,The mixture was added dropwise with stirring ethyl bromoacetate (665 g, 4.01 mol)After dropping,The reaction mixture was stirred for 24 hours at room temperature.The mixture is then suction filtered,The filter cake was washed three times with ethyl acetate,Each time with 500 ml.The filter cake was vacuum dried to give [Ph3PCH2CO2Et] + Br- (1500 g) as a white solid which was used directly in the next reaction,Yield 92%. |
92.6% | In ethyl acetate; at 13 - 18℃; for 21.5h; | Triphenyl phosphine (235.6 g, 0.90 mol) was dissolved in EtOAc (540 mL). Approximately 30 min was required for all of the solids to dissolve. The process was endothermic (solution cooled to 13 C. when the ambient temperature was 20 C.). A solution of ethyl bromoacetate (100 mL, 0.90 mol) in EtOAc (400 mL) was added dropwise over a 1.5 h period. A white precipitate formed during the addition. Stirred overnight (20 h) at ambient temperature (18 C.).The solids were collected by vacuum filtration rinsing with copious amounts of Et2O. Dried overnight in vacuo at 45 C. to give 3 as a white solid 356.3 g, 92.6% yield (0.83 mol). |
92.6% | In ethyl acetate; at 13 - 18℃; for 21.5h; | Triphenylphosphine (235.6 g, 0.90 mol) was dissolved in EtOAc (540 mL).It took about 30 minutes for all solids to dissolve. This process was endothermic (when the ambient temperature was 20 C., the solution was cooled to 13 C.).A solution of ethyl bromoacetate (100 mL, 0.90 mol) dissolved in EtOAc (400 mL) was added dropwise over 1.5 h.A white precipitate formed during the addition.And the mixture was stirred overnight (20 hours) at ambient temperature (18 C.).The solid was collected by vacuum filtration,And rinsed with a large amount of Et 2 O.Dry overnight at 45 C. under reduced pressure to afford 3 as a white solid (356.3 g) in 92.6% yield (0.83 mol). |
90.6% | In dichloromethane; at 20℃; for 72h; | The solution of triphenylphosphane (25.9 g, 98.8 mmol) indichloromethane (300 mL) was added ethyl 2-bromoacetate(15.0 g, 89.8 mmol) dropwise, and stirred at room temperaturefor 3 days. After the evaporation of the solvent, the remainingresidue was collected and washed with dichloromethane threetimes to give the corresponding Wittig reactant as a white solid(35.0 g, 90.6%). |
90.6% | In dichloromethane; at 20℃; for 72h; | Triphenylphosphine (25.9 g, 98.8 mmol) was dissolved in dichloromethane (300 mL)Ethyl 2-bromoacetate (15.0 g, 89.8 mmol) was added slowly,Reaction at room temperature for 3 days,Remove the solvent,The solid was washed with dichloromethane to give the product as a white solid,Yield 90.6%. |
89% | In ethyl acetate; at 20℃; | To a solution of triphenylphosphine (787 mg, 3.0 mmol) in EtOAc (10 mL) was added dropwise ethyl bromoacetate (388 muL, 3.5 mmol). The mixture was stirred at rt for overnight. The whole was filtered to give the target compound (1.15 g, 89%) as a white solid.1H NMR (500 MHz, CDCl3) delta: 7.94-7.89 (m, 6H), 7.81-7.78 (m, 3H), 7.70-7.66 (m, 6H), 5.60 (d, 2H, J = 13.4 Hz), 4.05 (q, 2H, J = 7.3 Hz), 1.08 (t, 3H, J = 7.3 Hz). FAB-MS m/z: 349 [M-Br]+. |
87% | In toluene; for 16h;Reflux; | Ethyl bromoacetate (1.98 mL, 17.90 mmol) was slowly added to a stirring solution of triphenylphosphine (5.64 g, 21.50 mmol) in toluene (20 mL). The reaction mixture was refluxed for 16 h and filtered. The filter cake was washed with ethyl acetate (3 x 20 mL) to give compound 2 (6.69 g, 87%). 1H NMR (CDC13, 400 MHz): delta 1.04 (t, J=7.2 Hz, 3H), 4.01 (q, J=7.2 Hz, 2H), 5.54 (d, J=13.6 Hz, 2H), 7.64-7.91 (m, 15H). |
87% | In toluene; for 16h;Inert atmosphere; Reflux; | Ethyl bromoacetate (1.98mL, 17.86mmol) was slowly added to a stirring solution of triphenylphosphine (5.64g, 21.50mmol) in toluene (20mL). The reaction mixture was refluxed for 16h and filtered. The filter cake was washed with ethyl acetate (3×20mL) to give phosphonium bromide (6.69g, 87%). 1H NMR (CDCl3, 400MHz): delta ppm 7.64-7.91 (m, 15H), 5.54 (d, J=13.6Hz, 2H), 4.01 (q, J=7.2Hz, 2H), 1.04 (t, J=7.2Hz, 3H). Into the solution of phosphonium bromide (6g, 13.98mmol) in CH2Cl2 (50mL) was added 1M NaOH aqueous solution (50mL, 50.00mmol). The mixture was vigorously stirred for 15min, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3×15mL). The combined organic phase was dried over Na2SO4 and concentrated to give compound 28 (4.28g, 88%). |
In benzene; | EXAMPLE 10 Triphenyl phosphine (13 g.) was dissolved in dry benzene (60 ml.) and ethyl bromoacetate (8.3 g.) was added dropwise. The solution was heated at 70 for 2 days, and then cooled and filtered. The residue was washed with benzene and dried to give about 16 g. of (ethoxycarbonylmethyl) triphenylphosphonium bromide. | |
In 1,2-dimethoxyethane; for 2h;Heating / reflux; | A mixture of triphenylphosphine (4.7 g, 18 mmol) and ethyl bromoacetate (20 ml, 18 mmol) in anhydrous dimethoxyethane is refluxed for 2 hour, concentrated and to the intermediate thus formed, sodium hydride (0.5 g) in dry ether at 0-5 C. is added with stirring to obtain intermediate ylide. An ethereal solution of 2-methyl-3-(3,4-methylenedioxyphenyl)-2E-propenal (2.5 g, 13 mmol) of formula 4 prepared in step (ii) above is added to ylide solution and after 24 hours an additional amount of sodium hydride (0.5 g) is added. The reaction mixture is continuously stirred for 72 hour at 40 C. On cooling, the contents are diluted with ethyl acetate (100 ml) to quench unused sodium hydride, then diluted with water (200 ml), organic layer separated and the aqueous layer extracted with ethyl acetate (2×100 ml). The combined organic layer washed with water (2×30 ml) and concentrated under reduced pressure. The crude 4-methyl-5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoate obtained above is hydrolysed directly without purification in 10% methanolic potassium hydroxide solution on a water bath for 3 hour, the contents concentrated and diluted with water (120 ml) and extracted with ethyl acetate (2×10 ml) and the aqueous layer acidified with 2N hydrochloric acid solution. The resulting precipitate is filtered, washed with water and air dried to furnish crude acid (2.40 g, 80%). Crystallisation of the crude acid from ethyl acetate: benzene (19:1) furnished pure 4-methyl-5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid of formula 6. | |
In ethanol; for 4h; | Ethyl bromoacetate (1.67 g, 1.11 mL, 10 mmol) and PPh3 (3.15 g, 12 mmol) were solved in dry EtOH (40 mL) and refluxed for 4 h. The mixture was cooled to room temperature, KOH (0.90 g, 16 mmol) and 2,4-dihydroxybenzaldehyde (1.31 g, 9.5 mmol) were added and the mixture was refluxed for 1.5 h. After evaporation in vacuo, the residue was suspended in water (50 mL) and acidified to pH 2. The aqueous phase was extracted with EtOAc (3 * 50 mL). The organic phase was dried, filtered and purified by column chromatography using CH2Cl2/MeOH (29:1) as eluent. The product was obtained as a white solid (0.42 g, 27%): mp 227-228 C (lit. mp 226.5-228 C); 49 1H NMR (500 MHz, DMSO-d6) delta 6.18 (d, 1H, 3J = 9.5 Hz, 3-H), 6.69 (d, 1H, 4J = 2.2 Hz, 8-H), 6.77 (dd, 1H, 4J = 2.2 Hz, 3J = 8.5 Hz, 6-H), 7.50 (d, 1H, 3J = 8.5 Hz, 5-H), 7.91 (d, 1H, 3J = 9.2 Hz, 4-H), 10.52 (br s, 1H, OH); 13C NMR (125 MHz, DMSO-d6) delta 102.3, 111.4, 111.5, 113.3, 129.8, 144.6, 155.7, 160.6, 161.4. LC-MS (ESI) (90% H2O to 100% MeOH in 10 min, then 100% MeOH to 20 min, DAD 220-400 nm), 98.1% purity, m/z = 163.30 ([M+H]+). | |
In toluene; at 20℃; | A 500 mL flask was charged with PPh3 (26.2 g, 100 mmol) and 250 mL of toluene. To this solution was added either ethyl bromoacetate or benzyl bromoacetate (100 mmol) over 40 minutes. The soultion was stirred for 2-3 hour at room temperature. The precipitate was filtered, washed with toluene (3×10 mL) and dried. The collected phosphonium salt was dissolved in H2O (400 mL) and one drop of phenolphthalein solution was added. The mixture was cooled in an ice bath and saturated aqueous NaOH solution was added dropwise until a permanent pink color was obtained. The solid was filtered and washed with cold H2O, collected and dried in vacuo to afford 2a-1 (yield: 95%) or 2b-1 (yield: 92%). | |
In water; at 90 - 100℃; for 1h;Inert atmosphere; | 39.3 g (150 mmol) of triphenylphosphane and 300 ml of water were placed in a 500 ml four-necked flask equipped with a stirrer and a thermometer and purged with nitrogen, 25.0 g (150 mmol) of ethyl 2-bromoacetateWhile dropping it at a temperature condition of 20 to 25 C., followed by stirring at 90 to 100 C. for 1 hour. The obtained aqueous solution was washed twice with 50 ml of toluene to obtain an aqueous solution of (1-ethoxycarbonylmethyl) triphenylphosphonium bromide. | |
In ethyl acetate; for 12h; | In a 500ml three-necked flask was added 47.2g of triphenylphosphine, 200ml of ethyl acetate, stirred for 10min,20ml ethyl bromoacetate was dissolved in 60ml of ethyl acetate and then added to the reaction mixture, resulting in a white precipitate, stirring was continued for 12h, after-treatment:After filtration, washing with diethyl ether and drying over anhydrous sodium sulfate, adding 200 ml of methylene chloride to dissolve, adding KOH aqueous solution (10 g KOH + 120 ml water)The aqueous phase was extracted twice with dichloromethane and the combined organics were dried over anhydrous sodium sulphate and the solvent methylene chloride was removed by rotary evaporation to give the first step crude phosphorus ylide. Its reaction formula 3 is as follows: | |
In chloroform; at 0 - 20℃; | General procedure: A dry two-necked flask was charged with a stirring bar, 3,5-dimethylphenol (1.22 g, 10 mmol), CH2Cl2 (30 mL), and pyridine (1.77 mL, 22 mmol). The mixture was cooled to 0 C, and bromoacetyl bromide (0.86 mL, 10 mmol) was added to the mixture slowly. The mixture was warmed to r.t. and stirred overnight. After the completion of the reaction (TLC monitoring), the mixture was washed with H2O (2 × 20 mL) and the organic phase was dried (Na2SO4). The solvent was removed and the residue was purified by flash chromatography on silicagel (c-Hex/EtOAc 10:1) to give 3,5-dimethylphenyl 2-bromoacetate (2.1 g, 86%) as a colorless oil. A dry two-neck flask was charged with PPh3 (786 mg, 3.0 mmol) and CHCl3 (10 mL). The solution was cooled to 0 C and the above prepared 3,5-dimethylphenyl 2-bromoacetate (729 mg, 3.0 mmol) was added. The reaction was warmed to r.t. and stirred overnight. The mixture was washed with aq 2 N NaOH (2 × 20 mL) and the collected organic phase was dried (Na2SO4). After removal of solvent under vacuum, the intermediate pure ylide was obtained as a white solid (1.20 g, 95%) and used in the next step without further purification. A dry Schlenk tube was charged with a stirring bar, CH2Cl2 (6 mL), the above prepared ylide (2.0 mmol), and Et3N (305 muL, 2.2 mmol). The mixture was cooled to 0 C in ice bath. A solution of acetyl chloride (2.2 mmol) in CH2Cl2 (2 mL) was added dropwise to the reaction mixture. The mixture was warmed to r.t. and stirred overnight. After the completion of the reaction (TLC monitoring), most of solvent was removed under vacuum, and Et2O (50 mL) was added to the flask, and the mixture was stirred for 0.5 h (Caution: longer reaction time may promote the isomerization of allenoate to the corresponding alkyl ester). The mixture was filtered and the organic phase was concentrated under vacuum. The residue was purified by flash chromatographyon silica gel (c-Hex/EtOAc 20:1) to give the allenoate 1e; yield: 147 mg (78%). | |
In 1,2-dimethoxyethane; for 2h;Heating / reflux; | (iii) Preparation of 4-methyl-5-(3,4-methylenedioxy phenyl^is, 4i?-pentadienoic acidA mixture of triphenylphosphine (4.7g, 18 mmol) and ethyl bromoacetate (20 ml, 18 mmol) in anhydrous dimethoxyethane is refluxed for 2 hour, concentrated and to the intermediate thus formed, sodium hydride (0.5g) in dry ether at 0-5 0C is added with stirring to obtain intermediate ylide. An ethereal solution of 2-methyl-3-(3,4~ methylenedioxyphenyl)-2E-propenal (2.5g, 13 mmol) of formula 4 prepared in step (ii) above is added to ylide solution and after 24 hours an additional amount of sodium hydride (0.5g) is added. The reaction mixture is continuously stirred for 72 hour at 40 EPO <DP n="23"/>C. On cooling, the contents are diluted with ethyl acetate (100ml) to quench unused sodium hydride, then diluted with water (200 ml), organic layer separated and the aqueous layer extracted with ethyl acetate (2x100 ml). The combined organic layer washed with water (2x30ml) and concentrated under reduced pressure. The crude 4- methyl-5-(3,4-methylenedioxyphenyl)-2.E,41s-pentadienoate obtained above is hydrolysed directly without purification in 10% methanolic potassium hydroxide solution on a water bath for 3 hour, the contents concentrated and diluted with water (120 ml) and extracted with ethyl acetate (2x10 ml) and the aqueous layer acidified with 2N hydrochloric acid solution. The resulting precipitate is filtered, washed with water and air dried to furnish crude acid (2.4Og, 80%). Crystallisation of the crude acid from ethyl acetate: benzene (19:1) furnished pure 4-methyl-5-(3,4- methylenedioxyphenyl)-2JE',4£'- pentadienoic acid of formula 6. | |
In toluene; for 12h;Inert atmosphere; | General procedure: The allenoates 2 were synthesized according to Kwon procedure.5 Under nitrogen atmosphere, to the solution of PPh3 (1.0 equiv) in toluene was added bromoacetic esters (1.0 equiv) over 15 minutes. The solution was stirred for 12 hours and the precipitate filtered, washed with ethyl acetate. The collected phosphonium salt was dissolved in dichloromethane and 2 M sodium hydroxide solution (1.0 equiv) was added. The mixture was stirred at room temperature for 20 minutes. The aqueous phase was extracted with dichloromethane. The combined organic extracts were washed with an aqueous saturated solution of sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude material was the desired compound 6, which was directly used in the next step. A 250 mL flask was charged with stabilized ylide 11 (1.0 equiv), trimethylamine (2.2 equiv) and dichloromethane under nitrogen atmosphere, the mixture was stirred at 0 C. The acid chloride (2.2 equiv) was added slowly as a solution in dichloromethane over 30 minutes. After completion of the reaction (TLC), the solution was treated with pentane. The mixture was filtered and the filtrate evaporated and passed through a short pad of silica gel (pentane/dichloromethane) to afford the pure allenoates 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Ethoxycarbonylmethyltriphenylphosphonium bromide(3.73 g, 8.72 mmol)And 2-light-1-naphthaldehyde(1.50 g, 8.72 mmol) in methanol(20 mL) was slowly added potassium carbonate(2 g) in methanol (20 mL)The reaction was stirred at room temperature for 6 h,Then concentrated.Dichloromethane (50 mL) and water (50 mL) were added. The aqueous phase was extracted with dichloromethane and the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product.The crude product was added to 2 mol / L potassium hydroxide (30 mL) and stirred for 2 h.Dichloromethane (50 mL) was added and the mixture was separated. The aqueous phase was acidified with dilute hydrochloric acid (2 mol / l), filtered, washed with water and dried to give 24 (1.34 g) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With Amberlite IR-400; In N,N-dimethyl-formamide; at 95℃; for 10h;Inert atmosphere; | General procedure: A round-bottom flask was charged with the suspension of ylide (1.5 mmol) in DMF (4 mL) and then Amberlite IR-400 (OH-) (1.2 g) was added to it. The content was stirred for the next 20 min at 95 C under inert atmosphere, then appropriate aldehyde (1 mmol) was added to the reaction mixture and heating was continued for next 10 h. On completion of the reaction (TLC [thin layer chromatography]), the resin was filtered off and the crude reaction mixture was evaporated to dryness. Isolation of the product was performed by flash chromatography (CombiFlash Rf 200i with UV/VIS and ELSD, Isco Teledyne Inc., USA) using RediSep column (SiO2). All the products were identified on the basis of their spectral data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triphenylphosphine In N,N-dimethyl-formamide at 20℃; for 20h; | |
98% | With sodium hydroxide In dichloromethane; water at 25℃; Sonication; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: 2-(benzo[d]oxazol-2-yl)acetonitrile; phenyl isothiocyanate With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 2h; Stage #2: (carbethoxymethyl)triphenylphosphonium bromide In N,N-dimethyl-formamide at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With Amberlite IR-400; In N,N-dimethyl-formamide; at 95℃; for 10h;Inert atmosphere; | General procedure: A round-bottom flask was charged with the suspension of ylide (1.5 mmol) in DMF (4 mL) and then Amberlite IR-400 (OH-) (1.2 g) was added to it. The content was stirred for the next 20 min at 95 C under inert atmosphere, then appropriate aldehyde (1 mmol) was added to the reaction mixture and heating was continued for next 10 h. On completion of the reaction (TLC [thin layer chromatography]), the resin was filtered off and the crude reaction mixture was evaporated to dryness. Isolation of the product was performed by flash chromatography (CombiFlash Rf 200i with UV/VIS and ELSD, Isco Teledyne Inc., USA) using RediSep column (SiO2). All the products were identified on the basis of their spectral data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate In dichloromethane; water at 25℃; Sonication; stereoselective reaction; | |
With triethylamine In dichloromethane at 20℃; for 16h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium carbonate; In dichloromethane; at 40℃; for 8h;Inert atmosphere; | General procedure: To a solution of ethyl bromoacetate (1.51 g, 9.0 mmol) in 1,2-dichloroethane (30 mL) was added 4-(diphenylphosphino)benzyltrimethylammonium bromide A (1.88 g, 4.5 mmol). The obtained mixture was stirred for 2 h at 60 C. After the reaction, ether was added and the mixture was stirred for 10 min at room temperature. Then, the mixture was filtered and washed with ether. Removal of the solvent from the filtrate gave phosphonium salt A1 in 95% yield. The obtained phosphonium salt A1 (358 mg, 0.6 mmol) was dried by a vacuum pump for 2 h at 70 C. To the flask containing phosphonium salt A1 was added a solution of p-chlorobenzaldehyde (70 mg, 0.5 mmol) in dichloromethane (4 mL) and K2CO3 (138 mg, 1.0 mmol). The obtained mixture was stirred for 8 h at 40 C under an argon atmosphere. After the reaction, ether (5 mL) was added and the obtained mixture was filtered and washed with ether. Removal of the solvent from the filtrate gave ethyl 3-(4'-chlorophenyl)propenoate (E/Z=96:4) in the crude state. The purity was estimated by 1H NMR and was 97%. Pure ethyl 3-(4'-chlorophenyl)propenoate was obtained in 94% yield by short flash column chromatography on silica gel (hexane/AcOEt=5:2). The co-product, 4-(diphenylphosphono)benzyltrimethylammonium bromide, was recovered by the above filtration in 98% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | General procedure: To the solution of 23 (26.0 g, 0.103 mol) in THF/MeOH/H2O (55:50:100 mL) was added LiOH?H2O (17.3 g, 0.411 mol, 4 equiv). The mixture was stirred for 1 h and concentrated. DCM was added. The organic layer was washed with 1 N HCl, saturated NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was washed with PE to give the product 51 (16.2 g, yield 80%). To the mixture of 51 (14.2 g, 67 mmol) and silica gel (14.2 g) in DCM (268 mL) was added PCC (21.6 g, 0.1005 mol, 1.5 equiv). The mixture was stirred for 2 h. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by silica gel chromatography to give the desired product 52 (11.8 g, 84.2%) as a solid. To the solution of 52 in DMSO (75 mL) were added Ph3PCH2OMe chloride (29.4 g, 3.6 equiv) in DMSO (75 ml) and t-BuOK (9 g, 3.4 equiv) in one portion. The mixture was stirred for 1 h at rt and 52 (5 g, 1 equiv) in DMSO (50 mL) was added in one portion at 0 C, and then stirred overnight. The reaction solution was poured into water, extracted with EA, washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel column to give 53 (4.1 g, yield 72%) as a yellow solid. TLC (silica gel plate, PE/EA = 10:1): Rf = 0.45. To the solution of 53 (2 g, 8.37 mmol) in THF (42 mL) was added HCl (6 N, 14 mL) at rt and the reaction was refluxed for 1 h. The reaction was cooled, poured into water, extracted with EA, washed with water, brine, dried over anhydrous Na2SO4 and evaporated to give 54 (2.54 g) as crude oil. TLC (silica gel plate, PE/EA = 10:1): Rf = 0.2. To the solution of 54 (2.54 g) in methanol (20 mL) was added NaBH4 (319 mg, 1 equiv) in portions for 10 min. The solution was stirred for 1 hand water (50 mL) was added for 10 min. The solution was extracted with EA, washed with water, dried over Na2SO4 and evaporated to give 55 (2.41 g) as crude oil. TLC (silica gel plate, PE/EA = 3:1): Rf = 0.3. To the solution of 55 (2.41 g) and Et3N (1.2 g, 1.1 equiv) in DCM (35 mL) was added acetyl chloride (0.84 g, 1 equiv) dropwise at 0 C. The reaction wasstirred at 0-C for 2 hand water (50 mL) was added to the reaction solution. The solution was extracted with EA and the organic layer was washed with brine, dried over anhydrous Na2SO4 andevaporated. The residue was purified by silica gel column (PE/EA = 10:1) to give the product 56 (2.2 g, 98% of three steps). 1HNMR(300 MHz, CDCl3): delta 7.57 (d, 1H), 7.48 (d, 1H), 7.37 (t, 1H), 4.32 (t, 2H), 3.15 (t, 2H), 2.03 (s, 1H) ppm. To the mixture of 56 (1 g), pin2B2 (1.04 g, 1.1 equiv) and KOAc (0.73 g, 2 equiv) in 1,4-dioxane (20 mL) was added Pd(dppf)Cl2 (100 mg, 5% equiv) under N2. The reaction was refluxed for 2 h. The reaction solution was cooled to rt, poured into water (50 mL) and extracted with EA. The organic phase was washed with water, brine, dried over anhydrous Na2SO2 and concentrated. The residue was purified by silica gel column (PE/EA = 10:1) to give 57 (0.9 g) as a colorless oil. TLC (silica gel plate, PE/EA = 3:1): Rf = 0.7. To the solution of 57 (1 g) in MeOH (20 mL) was added NaOH (0.254 g, 2 equiv) in one portion at 0 C. The reaction solution was stirred at rt for1 h. MeOH was rotary evaporated to give a residue that was mixed with HCl (6 N, 1.1 mL). The reaction was stirred overnight, quenched with NaOH (1 N, 10 mL), washed with EA. The aqueous phase was acidified with HCl (1 N) to pH 1-2 and extracted with EA. The combined organic layer was washed with brine, dried over Na2SO4, and evaporated to give 58 (540 mg, yield 51%) as a white solid. 1H NMR (300 MHz, DMSO-d6): delta 8.84 (s, 1H), 7.67 (d, 1H), 7.54 (m, 2H), 4.07 (t, 2H), 2.94 (t,2H). MS: m/z = 174 (M+1, ESI+). To the solution of 58 (540 mg, 3.12 mmol) in HCOOH/water (5.4:0.54 mL) was added Raney Ni. The reaction was stirred at 100 C for 1 h, cooled to rt, quenched with water and extracted with EA. The organic phase was washed with water, brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column (PE/EA = 3:1) to give 59 (460 mg, 85%) as a white solid. 1H NMR (300 MHz, DMSO-d6): delta 10.69 (s, 1H), 9.01 (s, 1H), 7.74 (q, 1H), 7.54 (m, 2H), 4.09 (t, 2H), 2.96 (t, 1H) ppm. MS:m/z = 177(M+1, ESI+). To the solution of Ph3PCH2COOCH2CH3 bromide in THF (6 mL) was added NaH (60%, 68 mg, 3 equiv). The reaction was stirred under N2 for 1 h at rt. Compound 59 (100 mg, 1 equiv) in THF (2 mL) was added in one portion at 0 C. The mixture was stirred overnight, quenched with water (10 mL) and HCl (1 N 10 mL), extracted with EA. The organic phase was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column (PE/EA = 10:1-3:1) to give 60 (140 mg, yield 98%) as a white solid. 1H NMR (300 MHz, DMSO-d6): delta 8.73 (s, 1H), 8.70 (d, 1H), 7.70 (d, 1H), 7.42 (t, 1H), 7.26 (d, 1H), 6.45 (d, 1H) 4.30 (q, 2H), 4.03 (t, 2H), 2.89 (t, 2H), 1.20 (t, 3H) ppm. MS: m/z = 255 (M+23, ESI+). T... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.5% | With sodium hydride In tetrahydrofuran; mineral oil at -5 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | To a solution of Ph3PCH2COOEt bromide (45 g, 106 mmol, 2.5 equiv) in DMSO (350 mL) was added t-BuOK (10.3 g, 85 mmol, 2 equiv). The mixture was stirred at rt for 1 h, and then to the mixture was added a solution of 24 (11 g, 42.45 mmol, 1 equiv) in DMSO (74 mL). The reaction was stirred at rt overnight, quenched with saturated NH4Cl and extracted with t-butyl methyl ether (TBME). The organic phase was washed with brine and dried over anhydrous Na2SO4. The residue after rotary evaporation was purified by column chromatography to give 25 (13.9 g, yield 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | NaH (570 mg, 14.24 mmol) was added portion wise to stirred anhydrous DMSO (10 ml_). The mixture was heated to 80C until evolution of gas ceased and then cooled to 0C. A solution of (carbethoxymethyl)- triphenylphosphonium bromide (3.05 g, 7.12 mmol) in DMSO (10 ml_) was then added and the mixture stirred at r.t for 30 min. The mixture was cooled to 0C and a solution of <strong>[113118-82-4]5-chloronicotinaldehyde</strong> (1 .0 g, 7.12 mmol) in DMSO (10 ml_) was added and the mixture was stirred at r.t for 1 h. The mixture was then poured into aqueous 1 M HCI and extracted into DCM (3 x 50 ml_). The organics were combined and washed with H2O (3 x 100 ml_) and brine (3 x 100 ml_), separated, dried (MgSO ) and concentrated. Purification by flash silica column chromatography (gradient elution /'-hex to 25% EtOAc in /-hex) gave the title compound as a yellow solid (1 .1 g, 57%). LCMS (ES+) 271 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | NaH (613 mg, 15.4 mmol) was added portion wise to stirred anhydrous DMSO (10 mL). The mixture was heated to 80C until evolution of gas ceased and then cooled to 0C. A solution of (carbethoxymethyl)- triphenylphosphonium bromide (3.29 g, 7.74 mmol) in DMSO (5 mL) was then added and the mixture stirred at r.t for 30 min. The mixture was cooled to 0C and a solution of <strong>[113293-70-2]2,6-dichloroisonicotinaldehyde</strong> (1 .35 g, 7.74 mmol) in DMSO (5 mL) was added and the mixture was stirred at r.t for 1 h. The mixture was then poured into aqueous 1 M HCI and extracted into DCM (3 x 50 mL). The organics were combined and washed with H2O (3 x 100 mL) and brine (2 x 100 mL), separated, dried (MgSO ) and concentrated. Purification by flash silica column chromatography (gradient elution /'-hex to 20% EtOAc in /-hex) gave the title compound as a yellow solid (1 .25 g, 66%). LCMS (ES+) 247 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium hydroxide; In water; at 20 - 50℃; for 0.5h;Inert atmosphere; Green chemistry; | General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sodium hydroxide; In water; at 20 - 80℃; for 0.5h;Inert atmosphere; Green chemistry; | General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium hydroxide; In water; for 8h;Inert atmosphere; Reflux; Green chemistry; | General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 °C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sodium hydroxide In water for 4h; Inert atmosphere; Reflux; Green chemistry; stereoselective reaction; | Typical Procedure for the Preparation of Compound 1 -Wittig-SNAr Reaction General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 °C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydroxide In water for 1h; Inert atmosphere; Reflux; Green chemistry; stereoselective reaction; | Typical Procedure for the Preparation of Compound 1 -Wittig-SNAr Reaction General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 °C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With sodium hydroxide In water at 20 - 30℃; for 0.2h; Inert atmosphere; Green chemistry; stereoselective reaction; | Typical Procedure for the Preparation of Compound 1 -Wittig-SNAr Reaction General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 °C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sodium hydroxide; In water; at 20 - 80℃; for 0.5h;Inert atmosphere; Green chemistry; | General procedure: To a 25 mL three-necked round-bottomed flask was added 4-fluoro-3-nitrobenzaldehyde (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With sodium hydroxide; In water; at 20 - 80℃; for 1.0h;Inert atmosphere; Green chemistry; | General procedure: To a 25 mL three-necked round-bottomed flask was added <strong>[42564-51-2]4-fluoro-3-nitrobenzaldehyde</strong> (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium hydroxide; In water; at 20 - 50℃; for 0.2h;Inert atmosphere; Green chemistry; | General procedure: To a 25 mL three-necked round-bottomed flask was added <strong>[42564-51-2]4-fluoro-3-nitrobenzaldehyde</strong> (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hydroxide; In water; at 20 - 50℃; for 0.2h;Inert atmosphere; Green chemistry; | To a 25 mL three-necked round-bottomed flask was added <strong>[42564-51-2]4-fluoro-3-nitrobenzaldehyde</strong> (2b, 0.1691 g, 1.0 mmol), NaOH(0.0600 g, 1.5 mmol), (2-ethoxy-2-oxoethyl)triphenylphosphoniumbromide (4a, 0.6440 g, 1.5 mmol), piperidine (3b, 0.2968mL, 3.0 mmol), and H2O (5 mL), then heated to 50 C. The reactionprogress was carefully monitored by TLC. After 10 min, thesolvent was evaporated under reduced pressure, and theresidue was purified by silica gel column chromatography.Ethyl (E)-3-(4-Morpholino-1-yl-3-nitrophenyl)acrylate (1a)Orange solid. HRMS: m/z calcd for C15H18N2O5 [M + H]:307.1294; found: 307.1293. 1H NMR (400 MHz, CDCl3): delta = 7.94(d, J = 2.01 Hz, 1 H), 7.60-7.56 (m, 2 H), 7.09 (d, J = 8.61 Hz, 1 H),6.36 (d, J = 15.96 Hz, 1 H), 4.25 (q, J = 7.12 Hz, 2 H), 3.85-3.82(m, 4 H), 3.12-3.10 (m, 4 H), 1.33 (t, J = 7.13 Hz, 3 H) ppm. 13CNMR (101 MHz, CDCl3): delta = 166.5 (s, 1 C), 146.6 (s, 1 C), 142.0 (s,1 C), 141.6 (s, 1 C), 132.6 (s, 1 C), 127.7 (s, 1 C), 126.0 (s, 1 C),120.5 (s, 1 C), 118.5 (s, 1 C), 66.5 (s, 2 C), 60.6 (s, 1 C), 51.4 (s, 2C), 14.3 (s, 1 C) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With Amberlite IR-400; In N,N-dimethyl-formamide; at 95℃; for 10h;Inert atmosphere; | General procedure: A round-bottom flask was charged with the suspension of ylide (1.5 mmol) in DMF (4 mL) and then Amberlite IR-400 (OH-) (1.2 g) was added to it. The content was stirred for the next 20 min at 95 C under inert atmosphere, then appropriate aldehyde (1 mmol) was added to the reaction mixture and heating was continued for next 10 h. On completion of the reaction (TLC [thin layer chromatography]), the resin was filtered off and the crude reaction mixture was evaporated to dryness. Isolation of the product was performed by flash chromatography (CombiFlash Rf 200i with UV/VIS and ELSD, Isco Teledyne Inc., USA) using RediSep column (SiO2). All the products were identified on the basis of their spectral data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With Amberlite IR-400; In N,N-dimethyl-formamide; at 95℃; for 10h;Inert atmosphere; | General procedure: A round-bottom flask was charged with the suspension of ylide (1.5 mmol) in DMF (4 mL) and then Amberlite IR-400 (OH-) (1.2 g) was added to it. The content was stirred for the next 20 min at 95 C under inert atmosphere, then appropriate aldehyde (1 mmol) was added to the reaction mixture and heating was continued for next 10 h. On completion of the reaction (TLC [thin layer chromatography]), the resin was filtered off and the crude reaction mixture was evaporated to dryness. Isolation of the product was performed by flash chromatography (CombiFlash Rf 200i with UV/VIS and ELSD, Isco Teledyne Inc., USA) using RediSep column (SiO2). All the products were identified on the basis of their spectral data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With Amberlite IR-400; In N,N-dimethyl-formamide; at 95℃; for 10h;Inert atmosphere; | General procedure: A round-bottom flask was charged with the suspension of ylide (1.5 mmol) in DMF (4 mL) and then Amberlite IR-400 (OH-) (1.2 g) was added to it. The content was stirred for the next 20 min at 95 C under inert atmosphere, then appropriate aldehyde (1 mmol) was added to the reaction mixture and heating was continued for next 10 h. On completion of the reaction (TLC [thin layer chromatography]), the resin was filtered off and the crude reaction mixture was evaporated to dryness. Isolation of the product was performed by flash chromatography (CombiFlash Rf 200i with UV/VIS and ELSD, Isco Teledyne Inc., USA) using RediSep column (SiO2). All the products were identified on the basis of their spectral data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.5% | To a suspension of NaOH (0.6 g, 15.4 mmol) inwater (1 mL) at 0 C was added 7 (3.3 g, 7.7 mmol) as a solution indichloromethane (10 mL) and the mixture was stirred for 40 min.The intermediate 6 (3.2 g, 7.7 mmol) was added as a solution indichloromethane (10 mL) drop wise over a period of 3 min. Thereaction was allowed to room temperature and stirred overnight.The mixture was diluted with water and was extracted withdichloromethane to afford the crude product which was purified byflash column chromatography on silica gel to yield 8 as a faintyellow solid (2.9 g, 77.5%). Mp 110e112 C. 1H NMR (300 MHz,Chloroform-d) d(ppm) 8.17 (d, J 15.9 Hz, 1H), 7.77 (dd, J 7.8,1.4 Hz, 1H), 7.61e7.51 (m, 3H), 7.45e7.33 (m, 14H), 7.21 (td, J 7.2,6.6, 4.1 Hz, 8H), 7.06e6.89 (m, 2H), 6.32 (d, J 15.9 Hz, 1H), 4.23 (q,J 7.1 Hz, 2H), 4.07 (q, J 7.1 Hz, 1H), 1.29e1.24 (m, 3H), 1.15 (t,J 7.1 Hz, 1H). MS (EI) m/z 485.3 [MH]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.5% | 5 (3.3 g, 7.7 mmol) was dissolved in dichloromethane (10 mL)Aqueous NaOH (0.6 g, 15.4 mmol) (1 mL) was added at 0 C,Stir at room temperature for 40 minutes.2- (1-Trityl- 1 H-imidazole) benzaldehyde (3.2 g, 7.7 mmol) was dissolved in dichloromethane (1 mL)0 C slowly dripped into the above system,After stirring for 12 hours at room temperature,Water (50 mL) was added,Dichloromethane extraction,Dried over anhydrous magnesium sulfate,Purification by column chromatography gave a pale yellow solid,Yield 77.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With sodium azide; potassium carbonate; In dimethyl sulfoxide; at 20℃; for 24h; | To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a; yield: 131 mg (75%); white solid; mp 92-94 C;R f = 0.55 (PE/EtOAc 1:1).1 H NMR (300 MHz, CDCl 3 ): delta = 7.87-7.85 (m, 2 H arom ), 7.48-7.47 (m, 3H arom ), 4.45 (q, J = 7.1 Hz, 2 H, OCH 2 CH 3 ), 1.38 (t, 3 H, J = 7.1 Hz,OCH 2 CH 3 ).13 C NMR (75 MHz, CDCl 3 ): delta = 161.1, 146.2, 134.1, 129.7, 129.3, 128.3,127.7, 61.7, 14.1.HRMS (ESI): m/z calcd for C 11 H 12 N 3 O 2 [M + H] + : 218.0924; found:218.0916. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium azide; L-proline; In dimethyl sulfoxide; at 20℃; for 24h; | General procedure: To a reaction flask equipped with a magnetic stir bar was added(ethoxycarbonylmethyl)triphenylphosphonium bromide (1a; 345 mg,0.8 mmol), benzaldehyde (2a; 128 mg, 1.2 mmol), NaN 3 (79 mg, 1.2mmol), and L-proline (9 mg, 0.08 mmol). The mixture was dissolvedin DMSO (5 mL) and stirred at r.t. for 24 h. After completion of thereaction, the mixture was poured into ice-water and extracted withEtOAc (4 × 20 mL). The combined organic layers were dried (Na 2 SO 4 ),and the solvent was concentrated in vacuo. The residue was isolatedby chromatography on silica gel with EtOAc/PE (1:2) as eluent to af-ford the product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | To a solution of (carbethoxymethy1)triphenylphosphonium bromide (9.2 g, 15.0 mmol) in 100 mL THF, tBuOK(2.3 g, 15.0 mmol) was added. The solution was stirred for 2 h, compound 7 (3.5 g, 15.0 mmol) was added, and stirring continued for 15 h. The mixture was evaporated under reduced pressure, and the residue was extracted with EtOAc (2 × 100.0 mL) and H2O (200.0 mL). The organic layer was concentrated and purified by chromatography(EtOAc/hexanes = 1:10) to afford (E)-ethyl 3-(4-bromonaphthalen-1-yl)acrylate as a colorless oil (yield 4.0 g, 87%).1H NMR (400 MHz, CHCl3): delta = 8.33 (d, J = 15.6 Hz, 1H),8.21-8.26 (m, 2H), 7.93 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 6.8 Hz,1H), 7.72-7.75 (m, 2H), 6.63 (d, J = 15.6 Hz, 1H). 13C NMR(100 MHz, CHCl3): delta = 167.2, 139.3, 131.8, 131.5, 131.1, 129.9,128.1, 128.0, 127.1, 125.7, 124.1, 123.9, 122.9. HRMS ((+)-ESI):m/z = 305.0159 (calcd. 305.0172 for C15H14BrO2, [M + H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | Stage #1: (E)-4-oxo-6-phenylhex-5-enoic acid With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0℃; Stage #2: (carbethoxymethyl)triphenylphosphonium bromide In dichloromethane at 45℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 4-(4-methoxy-phenyl)-4-oxo-butyric acid With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0℃; Stage #2: (carbethoxymethyl)triphenylphosphonium bromide In dichloromethane at 45℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 4-(4-chlorophenyl)-4-oxobutanoic acid With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0℃; Stage #2: (carbethoxymethyl)triphenylphosphonium bromide In dichloromethane at 45℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: 3-(3,4-dimethylbenzoyl)propionic acid With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0℃; Stage #2: (carbethoxymethyl)triphenylphosphonium bromide In dichloromethane at 45℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.1% | With sodium hydride In tetrahydrofuran at 0 - 25℃; for 6h; | 2.3; 4.4 Step 3: Synthesis of Intermediate VI-2 Dissolve ethoxyformylmethyltriphenylphosphonium bromide (42.9g, 0.1mol) and NaH (4.4g, 0.11mol) in tetrahydrofuran (400mL), and cool to 05,Drop 5-bromopyrazine-2-carbaldehyde (compound -2, 18.7g, 0.1mol)The tetrahydrofuran solution (200mL) was raised to 25°C after the addition was completed, and the reaction was incubated for 6 hours. The reaction was monitored by TLC. After the reaction was completed, water (100mL) was added to quench the reaction. Dry, filter, concentrate under reduced pressure,Purification by column chromatography (eluent: ethyl acetate/petroleum ether = 1/1) to obtain 20.0 g of oil (Intermediate VI-2) with a yield of 78.1%. |
Tags: 1530-45-6 synthesis path| 1530-45-6 SDS| 1530-45-6 COA| 1530-45-6 purity| 1530-45-6 application| 1530-45-6 NMR| 1530-45-6 COA| 1530-45-6 structure
A1267974[ 109376-35-4 ]
(Carbethoxymethyl-1,2-13C2)triphenylphosphonium bromide
Reason: Stable Isotope
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
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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P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
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. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
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 |
Sorry,this product has been discontinued.
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