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CAS No. : | 115551-33-2 | MDL No. : | MFCD03094310 |
Formula : | C6H5F2NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KRURHZHJEDNBCM-UHFFFAOYSA-N |
M.W : | 145.11 | Pubchem ID : | 2778441 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 32.79 |
TPSA : | 46.25 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.41 cm/s |
Log Po/w (iLOGP) : | 1.22 |
Log Po/w (XLOGP3) : | 1.09 |
Log Po/w (WLOGP) : | 2.1 |
Log Po/w (MLOGP) : | 1.68 |
Log Po/w (SILICOS-IT) : | 1.5 |
Consensus Log Po/w : | 1.52 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.87 |
Solubility : | 1.96 mg/ml ; 0.0135 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.65 |
Solubility : | 3.22 mg/ml ; 0.0222 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.0 |
Solubility : | 1.45 mg/ml ; 0.01 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.13 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
97% | palladium-carbon; | a)Synthesis of 2-hydroxy 3,4-difluoro aniline <strong>[82419-26-9]2,3 difluoro 6-nitro phenol</strong> (2 g, 11 mmol) was treated with 10% Pd/C(1 g) at 23 C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afforded the title compound (1.6 g, 97%). EI-MS m/z 146(M+H)+ |
97% | palladium-carbon; | a)Synthesis of 2-hydroxy 3,4-difluoro aniline <strong>[82419-26-9]2,3 difluoro 6-nitro phenol</strong> (2 g, 11 mmol) was treated with 10%Pd/C(1 g) at 23 C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afforded the title compound (1.6 g, 97%). EI-MS m/z 146(M+H)+ |
97% | palladium-carbon; | a) Synthesis of 2-hydroxy 3,4-difluoro aniline <strong>[82419-26-9]2,3 difluoro 6-nitro phenol</strong> (2 g, 11 mmol) was treated with 10%Pd/C (1 g) at 23 C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afforded the title compound (1.6 g, 97%). EI-MS m/z 146 (M+H)+ |
95% | With palladium on carbon; hydrogen; In ethanol; at 20℃; under 750.075 Torr; for 7h; | 2,3-Difluoro-6-nitrophenol (700mg, 4mmol) was dissolved in ethanol (5mL) and palladium on activated carbon (Pd/C) (84.8mg, 20%) was added. The reaction was stirred at room temperature under H2 atmosphere (1.0bar). After 7h, all starting material was consumed and Pd/C was filtered through Celite. The solvent was evaporated under reduced pressure to afford 6-amino-2,3-difluorophenol (550.5mg, 95% yield). 1H NMR (400MHz, CDCl3): delta (ppm) 6.59 (dt, J=8.6and 9.9 Hz, 1H), 6.47-6.31 (m, 1H), 4.27 (br s, 2H). ESI-HRMS: calc. for C6H6F2NO [M+H]+: 146.0412, found: 146.0418. |
95% | With palladium on carbon; hydrogen; In ethanol; at 20℃; under 750.075 Torr; for 7h; | 2,3-Difluoro-6-nitrophenol (700 mg, 4 mmol) was dissolved in ethanol (5 mL) and palladium on activated carbon (Pd/C) (84.8 mg, 20%) was added. The reaction was stirred at room temperature under H2 atmosphere (1.0 bar). After 7 h, all starting material was consumed and Pd/C was filtered through Celite. The solvent was evaporated under reduced pressure to afford 6-amino-2,3-difluorophenol (550.5 mg, 95% yield). 1H NMR (400 MHz, CDCl3): delta (ppm) 6.59 (dt, J=9.9, 8.6 Hz, 1H), 6.47-6.31 (m, 1H), 4.27 (br s, 2H). ESI-HRMS: calc. for C6H6F2NO [M+H]+: 146.0412, found: 146.0418. |
84% | With hydrogenchloride; tin(II) chloride dihdyrate; In methanol; water; at 0 - 20℃; for 48h; | To a solution of SnCl2·2H2O (32.1 g, 142.8 mmol) in methanol (100 mL) a concentrated hydrochloric acid (70 mL) and <strong>[82419-26-9]2,3-difluoro-6-nitrophenol</strong> 1 (5.0 g, 28.5 mmol) at 0 C were added. The reaction mixture was stirred at room temperature for 48 h, the solution has decolorated. Solution was neutralized with water NaHCO3 to pH 7, the formed colorless solid was filtered, dried at room temperature and extracted with ethyl acetate for several times. Water filtrate was extracted with ethyl acetate, combined organic lays were dried over anhydrous Na2SO4 and concentrated in vacuo. Yield of 2-amino-5,6-difluorophenol is 3.5 g (84%), mp. 128-130 C is in full agreement with the literature [6] . |
palladium-carbon; In methanol; | (a) A solution of <strong>[82419-26-9]2,3-difluoro-6-nitrophenol</strong> (500 mg) in methanol (7 ml) was hydrogenated over 5% Pd/C (60 mg) for 6 hours. The reaction mixture was filtered under nitrogen stream and the filtrate was evaporated under reduced pressure to give 414 mg of crude 2-amino-5,6-difluorophenol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In ethanol; at 20℃; | 6-Amino-2,3-difluorophenol (2) (550 mg, 3.8 mmol) was dissolved in ethanol (15 mL) and diethyl 2-(ethoxymethylene)malonate (819 mg, 3.8 mmol) was added. The reaction was stirred at room temperature until there was no starting material left. Ethanol was removed and the residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1/3 to 3/1) to give product 3 as a brown solid (1.04 g, 87%). 1H NMR (400 MHz, d6-DMSO): delta (ppm) 10.96 (d, J=14.0 Hz, 1H), 8.45 (d, J=13.9 Hz, 1H), 7.31-7.22 (m, 1H), 6.98-6.86 (m, 1H), 4.20 (q, J=7.1 Hz, 2H), 4.12 (q, J=7.1 Hz, 2H), 1.26 (t, J=7.1 Hz, 3H), 1.24 (t, J=7.1 Hz, 3H). ESI-MS: calc. for C14H14F2NO5 [M-H]-: 314.3, found: 314.3. |
In n-heptane; | Method 2 13.44 ml (66.34 mmol) of diethyl ethoxymethylenmalonate of are added to a solution of 9.6 g (66.34 mmol) of 3,4-difluoro-2-hydroxy-aniline [3] in 50 ml of n-heptane. The reaction mixture is reflux heated for 1 hour and then cooled at room temperature until a precipitate is obtained which is filtered at vacuum and washed with 20 ml of n-heptane. 17.5 g (81%) of diethyl (3,4-difluoro-2-hydroxyaniline)-methylenmalonate [4] are obtained and it does not need to be subject to a subsequent purification treatment. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With 1,1'-carbonyldiimidazole; | 3.50 6,7-Difluoro-3H-benzooxazol-2-one (97KK11) <strong>[115551-33-2]3,4-Difluoro-2-hydroxyaniline</strong> (0.329 g, 2.27 mmol) and carbonyldiimidazole (0.390 g, 2.41 mmol) were reacted according to GP7. Purified by flash CC (SiO2; DCM/MeOH 40:1) to give the title compound (97KK11) (0.139 g, 36%). 1H-NMR (MeOD) delta 6.83-6.80 (m, 1H), 7.08-7.01 (m, 1H); 13C-NMR (MeOD) delta 105.6 (J=4.5 Hz, J=7.8 Hz), 112.6 (J=20.3 Hz), 129.6, 133.1 (J 4.5 Hz, J=10.3 Hz), 136.7 (J=17.8 Hz, J=250.3 Hz), 148.1 (J=10.0 Hz, J=240.0 Hz), 156.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium 10% on activated carbon; In methanol; ethyl acetate; for 12h; | To a solution of 1,2,3-trifluoro-4-nitrobenzene (Aldrich, 15.0 g, 84.7 mmol) in DMF (25.0 mL) were added K2CO3 (17.6 g, 127.8 mmol) and benzylalcohol (8.8 mL, 85.0 mmol). The suspension was stirred overnight. To the reaction mixture was then added H2O (100 mL) and the solution was kept at 4 C. overnight. The precipitate was then collected and washed with H2O to give a mixture of two isomers (22.4 g) [1-(benzyloxy)-2,3-difluoro-4-nitrobenzene and 2-(benzyloxy)-3,4-difluoro-1-nitrobenzene in a ratio of 1: 1]. To a solution of [1-(benzyloxy)-2,3-difluoro-4-nitrobenzene and 2-(benzyloxy)-3,4-difluoro-1-nitrobenzene] (22.4 g, 84.5 mmol) in EtOAc (20.0 mL) and MeOH (100.0 mL) was added 10% Pd/C (1.0 g). The suspension was stirred under H2 atmosphere for 12 h. The suspension was then filtered and concentrated in vacuo to give a mixture of two isomers (12.6 g) [4-amino-2,3-difluorophenol and 6-amino-2,3-difluorophenol in a ratio of 1:1]. MS (ESI+): m/z 146.00 (M+H)+. | |
With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; for 26.8333h; | (Production Example 111) 4-Amino-2,3-difluorophenol To a solution of a mixture of 1-(benzyloxy)-2,3-difluoro-4-nitrobenzene and 2-(benzyloxy)-3,4-difluoro-1-nitrobenzene (6.54 g) in methanol (200 ml) was added 10 % palladium on carbon (654 mg), followed by stirring under a hydrogen atmosphere at room temperature for 26 hr and 50 min. The atmosphere in the reaction vessel was replaced with nitrogen to stop the reaction, and the catalyst was filtered off through Celite. The filtrate was concentrated under reduced pressure to provide the titled compound as a black solid (3.52 g) which was a mixture of 6-amino-2,3-difluorophenol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
b)Synthesis of N-(2-hydroxy 3,4-difluoro phenyl) N'-(2-bromo phenyl) urea The urea was prepared from <strong>[115551-33-2]2-hydroxy 3,4-difluoro aniline</strong>(0.290 g, 2 mmol) and 2-bromo phenyl isocyanate(0.4 g) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane(0.254 g, 37%). EI-MS m/z 343(M+H)+ | ||
b)Synthesis of N-(2-hydroxy 3,4-difluoro phenyl) N'-(2-bromo phenyl)urea The urea was prepared from <strong>[115551-33-2]2-hydroxy 3,4-difluoro aniline</strong>(0.290 g, 2 mmol) and 2-bromo phenyl isocyanate(0.4 g) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane(0.254 g, 37%). EI-MS m/z 343(M+H)+ | ||
b) Synthesis of N-(2-hydroxy 3,4-difluoro phenyl) N'-(2-bromo phenyl) urea The urea was prepared from <strong>[115551-33-2]2-hydroxy 3,4-difluoro aniline</strong> (0.290 g, 2 mmol) and 2-bromo phenyl isocyanate (0.4 g) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane (0.254 g, 37%). EI-MS m/z 343 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium hydroxide; In ethyl acetate; | EXAMPLE 3 Synthesis of 6-amino-2,3 difluoro-phenol [3] 60 ml of concentrated HCl, at room temperature and subject to magnetic agitation, are added to a solution of 2.85 g (11.66 mmol) of the compound [2] in 126 ml of ethylic ether. After 90 minutes, a solution of NaOH up to pH=6 is slowly added to the reaction mixture. The organic layer is separated and the aqueous one is extracted with more ethylic ether (3*25 ml). The combined ether extracts are washed with water (2*15 ml), dried on MgSO4 and the solvent is eliminated. 1.45 g (86%) of product [3] are obtained which can be used in the following stage without the need of a previous purification. Spectroscopic and physical data 1 H NMR (CDCl3): 6.54 (m, 1H, ArH); 6.42 (ddd, 1H, J=8.8, 4.8 and 1.9 Hz, ArH) and 4.2 (s wide, 2H, NH) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step A: 5-r4-fbenyloxy')phenyll-l-r2.4-dichlorophenylVN-f3.4-difluoro-2- hydiOxyphenyl)-4-methyl-lH-pyrazole-3-carboxamideOxalyl chloride (1 ml) was added to 5-[4-(benzyloxy)phenyl]-l-(2,4-dichlorophenyl)-4- methyl-lH-pyrazole-3-carboxylic acid (300 mg, 0.66 mmol) in DCM (5 ml). One drop of DMF was added and the reaction continued at room temperature for 4 hours. The solvent and excess oxalyl chloride was evaporated and the mixture suspended in 3 ml DCM and added to <strong>[115551-33-2]6-amino-2,3-difluorophenol</strong> (162 mg, 1.12 mmol) in DCM/K2CO3(10%, aq) (2:3, 5 ml). The reaction was continued at room temperature for 19 hours. DMAP (50 mg, 0.41 mmol) was added and the reaction continued at room temperature for 5 hours. The phases were separated and the organic phase washed with water and dried over MgSO4 (435 mg, crude). 1H NuMR (399.964 MHz) delta 10.00-9.60 (br, IH), 9.04 (s, IH), 7.45-6.58 (m, 14H), 5.02 (s, 2H), 2.37 (s, 3H). MS m/z 580, 582, 584 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In PPA; water; | The 5-bromo-3-(6,7-difluoro-1,3-benzoxazol-2-yl)pyridin-2-amine used as starting material was prepared as follows: To a mixture of 2-amino-5-bromo-pyridine-3-carboxylic acid (1 g) and <strong>[115551-33-2]6-amino-2,3-difluoro-phenol</strong> (0.669 g) placed in a round bottom flask was added polyphosphoric acid (10 g). The mixture was heated at 200 C. for 5 hours. A homogenous black mixture was obtained. The mixture was diluted in water and neutralizing to pH 8 with NaOH 2N. The heterogeneous mixture was diluted with dichloromethane. The insoluble was filtered. The organic phase was separated. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with brine, dried on sodium sulfate, evaporated and dried to afford 5-bromo-3-(6,7-difluoro-1,3-benzoxazol-2-yl)pyridin-2-amine (0.338 g). NMR Spectrum: (DMSOd6) 7.54 (ddd, 1H), 7.70 (ddd, 1H), 7.79 (bs, 2H), 8.34 (d, 1H), 8.38 (d, 1H); Mass spectrum: M+H+ 326-328 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With hydrogenchloride; In water; at 100℃; for 16h;Reflux; | To <strong>[115551-33-2]2-amino-5,6-difluorophenol</strong> 2 (2 g, 13.8 mmol) 6 N hydrochloric acid (10 mL) was added, the mixture was heated to 100 C, then crotonic aldehyde (1.2 mL, 14.3 mmol) was added slowly. The mixture was refluxed for 16 h, after cooling NH4OH was added under stirring to pH 8. Then ethyl acetate (50 mL) was added, and the reaction mixture was stirred during 30 min, the formed colorless solid was filtered. Filtrate was extracted with ethyl acetate, organic solution was concentrated in vacuo, and residue was recrystallized from hexane-ethanol (1:1). Yield of 2-methyl-5,6-difluoro-8-hydroxyquinoline is 1.36 g (51%), mp. 102-104 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In ethanol; at 20℃; | 6-Amino-2,3-difluorophenol (2) (550mg, 3.8mmol) was dissolved in ethanol (15mL) and diethyl 2-(ethoxymethylene)malonate (819mg, 3.8mmol) was added. The reaction was stirred at room temperature until there was no starting material left. Ethanol was removed and the residue was purified by flash column chromatography on silica gel (EtOAc/hexane=1/3 to 3/1) to give product 3 as a brown solid (1.04g, 87%). 1H NMR (400MHz, DMSO-d6): delta (ppm) 10.96 (d, J=14.0Hz, 1H), 8.45 (d, J=13.9Hz, 1H), 7.31-7.22 (m, 1H), 6.98-6.86 (m, 1H), 4.20 (q, J=7.1Hz, 2H), 4.12 (q, J=7.1Hz, 2H), 1.26 (t, J=7.1Hz, 3H), 1.24 (t, J=7.1Hz, 3H). ESI-MS: calc. for C14H14F2NO5 [M-H]-: 314.3, found: 314.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine In N,N-dimethyl-formamide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine In N,N-dimethyl-formamide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In N,N-dimethyl-formamide at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With tetra(n-butyl)ammonium hydrogensulfate; potassium carbonate In dichloromethane; water for 16h; | (±)-7,8-Difluoro-3-phenyl-3,4-dihydro-2H-1,4-benzoxazine (8) 2-Bromoacetophenone (4.84 g, 24.3 mmol) in CH2Cl2(50 mL) wasadded to a stirred solution of 6-amino-2,3-difluorophenol (3.49 g,24.0 mmol), Bu4NHSO4(277 mg, 0.814 mmol), and K2CO3(19.0 g, 138mmol) in H2O (140 mL) and CH2Cl2(140 mL). After 16 h, the layerswere separated, and the aqueous phase was extracted with CH2Cl2(2× 100 mL). The solvent was evaporated and the crude product was purified by column chromatography onsilica gel, eluting with petrol-EtOAc (95:5), to give the imine (4.5 g, 76%) as an amorphous solid; mp114-116 °C; 1H NMR (400 MHz, CDCl3): = 7.97-7.90 (m, 2 H), 7.59-7.47 (m, 3 H), 7.20 (ddd, J= 8.5, 5.5, 2.0 Hz, 1 H), 6.83 (ddd, J= 10.0,8.5, 7.5 Hz, 1 H), 5.15 (s, 2 H); 13C NMR (100 MHz, CDCl3): (one Ccould not be observed) = 158.2, 150.4 (dd, J= 248.5, 10.5 Hz), 139.5(dd, J= 250.5, 16.0 Hz), 134.9, 131.6, 131.1 (dd, J= 4.0, 2.0 Hz), 128.9,126.4, 122.1 (dd, J= 8.0, 3.5 Hz), 109.1 (d, J= 18.5 Hz), 62.6; 19F NMR(376 MHz, CDCl3): = -135.7 (d, J= 20.0 Hz, 1 F), -160.5 (d, J= 20.0Hz, 1 F). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C 4.1: Lux Cellulose-1 / hexane; isopropyl alcohol / Resolution of racemate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C 4.1: sparteine; n-butyllithium / hexane; toluene / 0.5 h / -78 °C 4.2: -78 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C 4.1: Lux Cellulose-1 / hexane; isopropyl alcohol / Resolution of racemate 5.1: trifluoroacetic acid / dichloromethane / 24 h / 20 °C | ||
Multi-step reaction with 5 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C 4.1: sparteine; n-butyllithium / hexane; toluene / 0.5 h / -78 °C 4.2: -78 - 20 °C 5.1: trifluoroacetic acid / dichloromethane / 24 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3: Daicel Chiralpak IA / hexane; isopropyl alcohol / Resolution of racemate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3: Daicel Chiralpak IA / hexane; isopropyl alcohol / Resolution of racemate 4: 26 h / 140 °C | ||
Multi-step reaction with 6 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C 4.1: Lux Cellulose-1 / hexane; isopropyl alcohol / Resolution of racemate 5.1: trifluoroacetic acid / dichloromethane / 24 h / 20 °C 6.1: 26 h / 140 °C | ||
Multi-step reaction with 6 steps 1.1: potassium carbonate; tetra(n-butyl)ammonium hydrogensulfate / dichloromethane; water / 16 h 2.1: sodium tetrahydroborate / water; ethanol / 3 h / 90 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 3.2: 16 h / -78 - 20 °C 4.1: sparteine; n-butyllithium / hexane; toluene / 0.5 h / -78 °C 4.2: -78 - 20 °C 5.1: trifluoroacetic acid / dichloromethane / 24 h / 20 °C 6.1: 26 h / 140 °C |
Tags: 115551-33-2 synthesis path| 115551-33-2 SDS| 115551-33-2 COA| 115551-33-2 purity| 115551-33-2 application| 115551-33-2 NMR| 115551-33-2 COA| 115551-33-2 structure
[ 1330750-27-0 ]
6-Amino-2,3-difluorophenol hydrochloride
Similarity: 0.97
[ 1330750-27-0 ]
6-Amino-2,3-difluorophenol hydrochloride
Similarity: 0.97
[ 1330750-27-0 ]
6-Amino-2,3-difluorophenol hydrochloride
Similarity: 0.97
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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. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
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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