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Synonyms: (S)-(+)-4-Phenyl-2-oxazolidinone
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CAS No. : | 99395-88-7 |
Formula : | C9H9NO2 |
M.W : | 163.17 |
SMILES Code : | [C@H]1(NC(OC1)=O)C2=CC=CC=C2 |
Synonyms : |
(S)-(+)-4-Phenyl-2-oxazolidinone
|
MDL No. : | MFCD00043396 |
InChI Key : | QDMNNMIOWVJVLY-MRVPVSSYSA-N |
Pubchem ID : | 730424 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-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 |
---|---|---|
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; lithium chloride; In ethyl acetate; at 75℃; for 20h; | A 20 L jacketed reactor was fitted with a reflux condenser and a nitrogen inlet. To the flask was charged 1006 g (8.81 mol) of (E) -2-methyl-2-pentenoic acid, 1250 g (7.661 mol) of (S)- (+)-4-phenyl-oxazolidin-2-one, 2179 g (8. 81 mol) of 2-ethoxy-1- ethoxycarbonyl-1, 2-dihydroquinoline (EEDQ), 81 g (1.915 mol) of lithium chloride, and 12.5 L of ethyl acetate (EtOAc). The reaction was heated to 75 0 C for 20 hours and then cooled to room temperature. The reaction solution was extracted 3x with 4 L aliquots of 1N HC1 and lx with 4 L of 0.2N NaOH. The 20 L reactor was fitted with a distillation head. The organic layer was distilled to remove, in succession: 6.5 L of EtOAc, after which 8 L of heptane was added back to the reactor; 4 L of EtOAc/heptane, after which 4 L of heptane was added to the reactor; and 4 L of EtOAc/heptane, after which 8 L of heptane was added to the reactor. After an additional 2 L of EtOAc/heptane was removed by distillation, the reaction mixture was cooled to an internal temperature of 40°C, and the reactor contents were charged to a filter and filtered under 5 psig of nitrogen washing with 8 L of heptane. The solids were dried under 5 psig of nitrogen overnight to give 1772 g of the titled compound : 1H-NMR (DMSO) 7.363-7. 243 (m, 5H), 6.137-6. 096 (m, 1H), 5.434-5. 394 (m, 1H), 4.721-4. 678 (t, 1H, J = 8.578), 4. 109-4. 069 (m, 1H), 2.119- 2.044 (m, 2H), 1.703-1. 700 (d, 3H, J = 1. 364), 0.945-0. 907 (t, 3H, J = 7.603) ; Anal Calc'd for Cl5Hl7Nl03 : C, 69.48 ; H, 6.61 ; N, 5.40. Found: C, 68.66 ; H, 6.60 ; N, 5.60 ; MS (Ion Mode: APCI) ? iZ= 260 [M+l l+. | |
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; lithium chloride; In ethyl acetate; at 75℃; for 20h; | A 20 L jacketed reactor was fitted with a reflux condenser and a nitrogen inlet. To the flask was charged 1006 g (8.81 mol) of (E)-2-methyl-2-pentenoic acid, 1250 g (7.661 mol) of (S)-(+)-4-phenyl-oxazolidin-2-one, 2179 g (8.81 mol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), 81 g (1.915 mol) of lithium chloride, and 12.5 L of ethyl acetate (EtOAc). The reaction was heated to 75°C for 20 hours and then cooled to room temperature. The reaction solution was extracted 3x with 4 L aliquots of 1 N HCI and 1 x with 4 L of 0.2N NaOH. The 20 L reactor was fitted with a distillation head. The organic layer was distilled to remove, in succession: 6.5 L of EtOAc, after which 8 L of heptane was added back to the reactor; 4 L of EtOAc/heptane, after which 4 L of heptane was added to the reactor; and 4 L of EtOAc/heptane, after which 8 L of heptane was added to the reactor. After an additional 2 L of EtOAc/heptane was removed by distillation, the reaction mixture was cooled to an internal temperature of 40°C, and the reactor contents were charged to a filter and filtered under 5 psig of nitrogen washing with 8 L of heptane. The solids were dried under 5 psig of nitrogen overnight to give 1772 g of the titled compound: 1H-NMR (DMSO) 7.363- 7.243 (m, 5H), 6.137-6.096 (m, 1 H), 5.434-5.394 (m, 1 H), 4.721-4.678 (t, 1 H, J = 8.578), 4.109-4.069 (m, 1H), 2.119-2.044 (m, 2H), 1.703-1.700 (d, 3H, J = 1.364), 0.945-0.907 (t, 3H, J = 7.603) ; Anal Calc'd for C15H17N1O3: C, 69.48; H, 6.61; N, 5.40. Found: C, 68.66; H, 6.60; N, 5.60; MS (Ion Mode: APCI) m/z= 260 [M+1]+. | |
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; lithium chloride; In ethyl acetate; at 75℃; for 20h; | A 20 L jacketed reactor was fitted with a reflux condenser and a nitrogen inlet. To the flask was charged 1006 g (8.81 mol) of (E) -2-methyl-2-pentenoic acid, 1250 g (7.661 mol) of (S)-(+)-4-phenyl-oxazolidin-2-one, 2179 g (8.81 mol) of 2-ethoxy-1-ethoxycarbonyl-1,2- dihydroquinoline (EEDQ), 81 g (1.915 mol) of lithium chloride, and 12.5 L of ethyl acetate (EtOAc). The reaction was heated to 75°C for 20 hours and then cooled to room temperature. The reaction solution was extracted 3x with 4 L aliquots of IN HCI and 1x with 4 L of 0.2N NaOH. The 20 L reactor was fitted with a distillation head. The organic layer was distilled to remove, in succession: 6.5 L of EtOAc, after which 8 L of heptane was added back to the reactor; 4 L of EtOAc/heptane, after which 4 L of heptane was added to the reactor; and 4 L of EtOAc/heptane, after which 8 L of heptane was added to the reactor. After an additional 2 L of EtOAc/heptane was removed by distillation, the reaction mixture was cooled to an internal temperature of 40°C, and the reactor contents were charged to a filter and filtered under 5 psig of nitrogen washing with 8 L of heptane. The solids were dried under 5 psig of nitrogen overnight to give 1772 g of the title compound: 'H-NMR (DMSO) 8 7.363-7.243 (m, 5H), 6.137-6.096 (m, 1H), 5.434-5.394 (m, 1H), 4.721-4.678 (t, 1H, J = 8.578), 4.109-4.069 (m, 1H), 2.119-2.044 (m, 2H), 1.703-1.700 (d, 3H, J = 1.364), 0.945-0.907 (t, 3H, J = 7.603); Anal Calc'd for C15H17N1O3: C, 69.48; H, 6.61; N, 5.40. Found: C, 68.66; H, 6.60; N, 5.60; MS (Ion Mode: APCI) m/z= 260 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; | Example 1: Preparation of ezetimibe; (1-1) Preparation of 3-[5-(fluorophenyl)-l,5-dioxapentyl]-4(S)- phenyl-2-oxazolidinone (Formula 7); 200 g of <strong>[149437-76-3]5-(4-fluorophenyl)-5-oxopentanoic acid</strong> of formula 8, 16O g of (S)-4-phenyloxazolidine-2-one of formula 9, and 11.6 g of 4-dimethylaminopyridine were dissolved in 600 m£ of dichloromethane to prepare a reaction mixture. A solution which was prepared by dissolving 157 g of N,N'-dicyclohexylcarboimide in 200 ml of dichloromethane was added to the reaction mixture and stirred for 2 hours. After completion of the reaction, the resulting reaction mixture was filtered to remove by-products. The filtrate thus obtained was washed successively with 1 I of 6N HCl, 1 ? of water, and 1 ? of saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered, and distilled under a reduced pressure to remove the solvent. The residue thus obtained was dissolved in 2 I of methanol by heating and cooled to induce crystallization. 2 £ of water was added thereto and stirred for 30 min. The solid thus obtained was isolated by filtering to obtain 289 g of the title compound as a white solid (yield: 86%).1H NMR(300MHz, CDCl3) : delta 7.92 (2H, M), 7.35-7.13 (5H, m), 7.04 (2H, m), 5.43 (IH, q), 4.75(1H, t), 4.22 (IH, q), 3.05-2.93 (4H, m), 2.03 (2H, m) |
85.7% | 5-(4-Fluorophenyl)-5-oxopentanoic acid (21.02 g, 100.0 mmol) and 4 dimethylamino- pyridine (16.25 g, 133.0 mmol) were dissolved in N,N-dimethylformamide (100 mL, 1.0 M) to afford a copious white precipitate suspended in solution. The reaction was cooled to 2 0C (ice/water bath), and trimethylacetyl chloride (16.40 mL, 16.04 g, 133.0 mmol) was added drop-wise to afford a pale yellow mixture. The rate of addition was controlled in order to keep the temperature at or below 5 0C. A heavy white precipitate was formed and the mixture was allowed to warm to room temperature and stirred for 1.5 h. The mixture was charged with (6)-(+)-4-phenyl-2- oxazolidinone (16.32 g, 100.0 mmol) and 4-dimethylaminopyridine (12.22 g, 100.0 mmol) both as solids to afford a yellow colored suspension. The reaction was stirred at 30 C - 35 0C for 2 h. An aliquot was removed for analysis by TLC and HPLC. The pale olive colored suspension was poured into water (400 mL) while stirring vigorously and cooling the mixture in an ice-brine bath, transferred with water (150 mL) and stirred with ice-cooling for 1.5 h to afford a solution with an off-white precipitate. The compound was filtered, transferred with water (2 x 25 mL), washed with water (50 mL) and air dried for 15 min to afford an off-white moist clumpy powder. The material was crystallized from isopropanol (58.0 mL; 1.6 mL/g theoretical yield) by heating to near reflux to afford a golden yellow colored solution. The solution was cooled slowly to room temperature over 12 h, a seed crystal was added and crystals began to precipitate. The mixture was cooled in an ice/water bath and stirred for 1 h. The crystals were filtered, transferred with cold isopropanol (2 x 10 mL), washed with cold isopropanol (25 mL), air dried and vacuum dried to constant weight to afford (45)-4-phenyl-3-[5-(4-fluorophenyl)-5-oxopentanoyl]-l,3- oxazolidin-2-one (30.46 g, 85.7 % yield) as a white crystalline solid; m.p. 91.0 0C; EPO <DP n="43"/>R/ 0.40 (1:2 ethyl acetate-hexane); HPLC Rr7.02 min; HPLC purity 94 %. 1H NMR (300 MHz, CDCl3) delta 7.93 (dd, J= 5.4, 9.0 Hz, 2H), 7.28-7.42 (m, 5H), 7.10 (dd, J= 8.5, 9.0 Hz, 2H), 5.43 (dd, J= 3.7, 8.7 Hz, IH), 4.70 (t, J= 8.9 Hz, IH), 4.28 (dd, J= 3.7, 8.7 Hz, IH), 3.05 (dt, J= 1.2, 7.3 Hz, 2H), 2.97 (t, J= 7.3, 2H), 2.05 (p, J= 7.3 Hz, 2H), ppm. | |
85% | To the soulution of compound 2 (700 g, 3.33 mol, 1.1 eq) dissolved in THF (5 L) was added triethylamine (1.2 L, 7.87 mol, 2.6 eq) at room temperature under N2 atmosphere. Then the solution of pivalic acid chloride (400 g, 3.33 mol, 1.1 eq) in THF (700 mL) was added dropwise to the reaction mixture cooled to -10 C for about 2 h. After addition, the mixture was stirred for 2 h at this temperature. TLC showed the compound 2 was consumed up, then the Evans auxiliary (493.5 g, 3 mol, 1 eq) and anhydrous LiCl (150.5 g, 3.5 mol,1.17 eq) were added sequencely. The mixture was warmed to room temperature and stirred for 2 h till the anhydride intermediate was consumed up. Then ethylacetate (2 L) and NH4Cl aq (1 L) were added, stirred for 15 min, stayed and separated, the aqueous layer was extracted with ethyl acetate (500 mL×2), combined the organic phase, washed with water (250 mL ×2), concentrated.The residue was recrystallized from isopropanol (7 L) to afforded compound 4 as a white solid (913.6 g, 85.0% yield). HPLC purity: 99.2%, mp: 94-95 C [lit.9(b) 91C]. 1H-NMR (CDCl3,400 MHz): delta 7.94-7.93 (m, 2H, J=2), 7.40-7.29 (m, 5H), 7.10-7.01 (m, 2H), 5.45-5.41 (m, 1H), 4.72-4.63 (m, 1H), 4.30-4.27 (m, 1H), 3.06 (t, 2H, J=8), 2.97 (t, 2H, J=12), 2.10-2.03 (m, 2H). 13C-NMR (CDCl3, 100MHz): delta 197.7, 172.2, 167.0, 164.4, 153.8, 139.2, 133.3, 130.7, 130.6, 129.2, 128.7, 126.0, 115.7, 115.5, 70.1, 57.6, 37.3, 34.8, 18.5. MS (ESI) m/z calcd. for C20H18FNO4: 355.12, calcd. for C20H18FNO4Na (M+Na)=378.12, found 378.04 (M+Na). |
70% | Compound I (21 g, 0.1 mol) was added to a 500 ml three-necked flask, Triethylamine 20 ml and dichloromethane 250 ml, Stuttgart dropwise pivaloyl chloride (14.4g, 0.12mol), (4S) -4-phenyl-2-oxazolidinone (24.5 g, 0.15 mol), DMF 5 ml, 4,4-dimethylaminopyridine (1.22 g, 0.01 mol) was added after refluxing for 3 h, After refluxing for 10 h, Ice bath cooling, Then, 200 ml of 5 M hydrochloric acid was added dropwise at 0 C, Static stratification, The lower methylene chloride layer was washed successively with saturated sodium bicarbonate solution and water, Dried over anhydrous sodium sulfate. The filtrate was concentrated to dryness, To give 24.9 g of a white solid compound II, Yield 70%. | |
68% | The compound (4) (30 g, 142.72 mmol) Triethylamine (26 g, 256.91 mmol) was dissolved in dichloromethane (150 ml)Cooling to 5 to 10 C, dropwise addition of pivaloyl chloride (17.3g, 142.62mmol), System has exothermic, 30min drop finished,5 to 10 deg C insulation reaction 2h, To the reaction system was added (S) -4-phenyl-2-oxazolidinone (23.3 g, 142.76 mmol) DMAP (2.4 g, 19.63 mmol), DMF (15 ml),Exothermic The temperature rose to 15 C, Heated to 45 reflux reaction 3h, Down to room temperature, Plus dichloromethane (150 ml), The organic phase was washed with water (60 ml) 1N hydrochloric acid (120 ml) Water (60ml) 2.5% aqueous sodium hydroxide solution (180 ml) Add water (50ml) wash, Organic phase concentrated dry, Plus isopropyl alcohol (60 ml), Stirring for 24 h, Filter, Add isopropyl alcohol (10ml) leaching, To give a white solid, I.e. compound (5) (34.4 g, 68% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
This invention adopts the "one-pot synthesis" according to bookletmai Bu intermediates for the synthesis of (4S)-3-[ (5S)-5-(4-fluoro phenyl)-5-hydroxy- fifth heavenly stem acyl group ]-4-phenyl -1, 3-oxygen nitrogen heterocyclic pentane-2-one (II), has the advantage of short synthetic route. One-pot synthesis (one-potreaction) is a high-efficiency organic synthetic method. "One-pot synthesis" in the reaction step from the reaction can be a plurality of relatively simple proceeding easily available raw materials, without intermediate separation, direct access to the molecules of the complex structure, thus having the advantage of the cost of synthesizing, and friendly to the environment.Firstly the 42g compound (I) dissolved in 420 ml in the reaction solution. The reaction solution includes: tetrahydrofuran, chloroform, dioxane or dichloromethane, and most preferably dichloromethane. In this embodiment, the reaction solution is dichloromethane, then added into the 1L three-necked bottle , will three-necked bottle is placed over the magnetic stirring device to mix uniformly to perform mechanical stirring. Compound (I) shown in the chemical structural formula as follows:In three-necked bottle is placed in the ice bath, ice-bath temperature is kept at 0 C three-necked bottle in until the oven is not higher than 10 C. Successive adds by drops Fu Suanji 30 ml and pivalyl chloride 75 ml. In this embodiment, the fu Suanji in particular to triethylamine. three-necked bottle is maintained during the dropping of the oven is not higher than 15 C. fu Suanji can absorb the acid generated in the reaction, a weakly alkaline substance with an acid salt, avoid acid influence the reaction or reaction balance. fu Suanji including triethylamine, pyridine, sodium methoxide or potassium hydroxide, and most preferably triethylamine. pivalyl chloride is an acylation reagent, pivaloyl chloride in organic synthesis in organic molecules can be oxygen, nitrogen, carbon, sulfur atom is introduced to the acyl.Triethylamine and pivalylchlorine instillment to room temperature reaction after 4 hours. Adding ice-bath to the oven is not higher than 10 C, dropwise S-4-phenyl-2-oxazolidinone 20g and N, N-dimethyl formamide 200 ml of the mixed solution, keep three-necked bottle the oven is not higher than 20 C, dropping temperature to reflux temperature of the reaction 2 hours. S-4-phenyl-2-oxazolidinone is an important pharmaceutical intermediates, is mainly used for asymmetric chiral organic synthesis.Salt bath to the oven is not higher than 0 C, successive instillment borane dimethyl sulfide 15 ml and (R)-2-methyl-CBS-oxazole borane 7.5 ml, maintain the oven is not higher than in three-necked bottle 5 C, after dropping temperature to stirring the mixture at room temperature for 30 minutes, add 150 ml dichloromethane, the reaction continued at room temperature for 3 hours. Borane dimethyl sulfide with synthesizing chiral the positioning function.Dropwise 300 ml quenching reaction of methanol, is added to the system again 100ml5% hydrogen peroxide and 20ml2N sulfuric acid, stirring 30 minutes, the organic layer is separated. Using 200ml2N sulfuric acid and 500ml5% wash once all sodium bisulfite solution, concentrating the organic layer to dry. Wherein F is fluoro, Ph is phenyl.Then using 200 ml isopropanol to dissolve residue, dripping 40 ml deionized water. Solid precipitated gradually during the dropping, the stirring at room temperature dropwise 2-3h, filtered, the filter cake drying to obtain 45g white solid.Detection method: high performance liquid chromatography (China Pharmacopoeia 2015 year version of the two-section appendix VD).Octadecyl silane bonds and silica gel as a filler, with cheap acetonitrile mobile phase, column temperature is 40 C, detection wavelength of 245 nm, flow rate is 0.5 ml/min. Isomer and weighed amount of product, respectively, using the mobile phase containing the dissolved and diluted into 0.01 mg/ml, diastereoisomer 0.01 mg/ml, isomer 0.01 mg/ml solution, as the system application solution. Applicability of system solution precision measuring 20ul, into the liquid chromatograph, and record chroatogram, diastereoisomer, vigiv, isomer peak in turn, non-enantiomer of the retention time of about 20 min, the main peak of the retention time of about 15 min, isomer produces the peak about 25 min, the main peak and the degree of separation of the isomer should be more than 2.0.The product weighed for proper amount of mobile phase containing the dissolved and diluted to 1.0 mg/ml solution is used for the solution of the sample. Sample solution taking precise quantity 20ul, into the liquid chromatograph, calculated normalization according to the area, such as in the chromatogram of the sample corresponding to isomer chromatographic peaks, the peak area of the isomer should not be more than the main peak and the sum of the peak area of 0.1%.Chromatographic conditions and system suitability test: with octadecyl silane bo... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.3% | With 2-chloro-1-methylpyridinium p-toluenesulfonate; triethylamine; In dichloromethane; at 25℃; for 5h; | Add 10 ml of dichloromethane, 500 ml of triethylamine (3.6 mol), and phenyloxazolidinone 163 g to a 5-liter four-necked bottle.(1 mol), propionic acid 80 g (1.1 mol), 300 g (1 mol)2-chloropyridine methyl p-toluenesulfonate salt 1000 ml of dichloromethaneThe solution was added and stirred at 25 C for 5 hours. TLC showed the reaction was complete, and the mixture was extracted with water and washed with water and saturated brine.The organic phase was dried over anhydrous sodium sulfate, concentrated, and then recrystallised to give product 200 g, yield: 91.3%, HPLC purity >99%. |
Tags: (S)-4-Phenyloxazolidin-2-one | (S)-(+)-4-Phenyl-2-oxazolidinone | Oxazolidines | Chiral Building Blocks | Aryls | Amides | Carbamates | Organic Building Blocks | Asymmetric Synthesis | Heterocyclic Building Blocks | 99395-88-7
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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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