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CAS No. : | 341-41-3 | MDL No. : | MFCD00051473 |
Formula : | C10H6BrF | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VAUJZKBFENPOCH-UHFFFAOYSA-N |
M.W : | 225.06 | Pubchem ID : | 67647 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 51.61 |
TPSA : | 0.0 Ų |
GI absorption : | Low |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | Yes |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -4.86 cm/s |
Log Po/w (iLOGP) : | 2.47 |
Log Po/w (XLOGP3) : | 3.96 |
Log Po/w (WLOGP) : | 4.16 |
Log Po/w (MLOGP) : | 4.45 |
Log Po/w (SILICOS-IT) : | 4.06 |
Consensus Log Po/w : | 3.82 |
Lipinski : | 1.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -4.35 |
Solubility : | 0.0101 mg/ml ; 0.000045 mol/l |
Class : | Moderately soluble |
Log S (Ali) : | -3.66 |
Solubility : | 0.0492 mg/ml ; 0.000219 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.21 |
Solubility : | 0.00138 mg/ml ; 0.00000615 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.51 |
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 |
---|---|---|
91.5% | for 2 h; Reflux | 1-Fluoronaphthalene (20.0 g, 0.137 mol) and carbon tetrachloride (120.0 mL) were added to a 500 mL one-necked flask, and bromine (10.9 g, 0.068 mol) was added dropwise and refluxed for 2 h. After completion of the reaction, the concentrated solution was concentrated under reduced pressure, and the concentrated solution was poured into methanol (80.0 mL). The solid was precipitated at room temperature overnight, and 28.2 g of 1-bromo-4-fluoronaphthalene. The yield was 91.5percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.2% | With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.5 h; | In a 500 mL three-necked flask, 1-bromo-4-fluoronaphthalene (27.9 g, 0.124 mol) was dissolved in anhydrous tetrahydrofuran (200.0 mL), triisopropyl borate (26.8 g, 0.142 mol) was added, cooled to -78 ° C, n-butyllithium (9.5 g, 0.149 mol) was added at -78 ° C for 0.5 h and then returned to room temperature. The reaction was quenched by adding saturated aqueous ammonium chloride solution. The pH was strongly acidic and extracted with ethyl acetate (200.0 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was beaten with n-hexane and filtered to obtain 21.2 g of a 4-fluoronaphthalene-1-boronic acid solid in a yield of 90.2percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 0.5 h; | In a 500 mL three-necked flask, 1-bromo-4-fluoronaphthalene (28.1 g, 0.125 mol) was dissolved in anhydrous tetrahydrofuran (200.0 mL), tri-n-butyl borate (35.9 g, 0.156 mol) was added, cooled to -78 ° C, n-butyllithium (10.4 g, 0.162 mol) was added to the solution at -78 ° C for 0.5 h and then returned to room temperature. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution. The pH was strongly acidic and extracted with ethyl acetate (200.0 mL × 3). The combined organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was beaten with n-hexane and filtered to give 21.3 g of 4-fluoronaphthalene-1-boronic acid in 90percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.6% | With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 1 h; | In a 500 mL three-necked flask, 1-bromo-4-fluoronaphthalene (24.6 g, 0.109 mol) was dissolved in anhydrous tetrahydrofuran (200.0 mL), trimethyl borate (12.5 g, 0.120 mol) was added, cooled to -78 ° C, n-butyllithium (7.7 g, 0.120mol). After 1 h at -78 ° C, the reaction was allowed to recover to room temperature. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution. The pH was strongly acidic and extracted with ethyl acetate (200.0 mL × 3). The combined organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was slurried with n-hexane and filtered to obtain 18.4 g of a 4-fluoronaphthalene-1-boronic acid solid in a yield of 88.6percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.5% | With tetrachloromethane; bromine; for 2h;Reflux; | 1-Fluoronaphthalene (20.0 g, 0.137 mol) and carbon tetrachloride (120.0 mL) were added to a 500 mL one-necked flask, and bromine (10.9 g, 0.068 mol) was added dropwise and refluxed for 2 h. After completion of the reaction, the concentrated solution was concentrated under reduced pressure, and the concentrated solution was poured into methanol (80.0 mL). The solid was precipitated at room temperature overnight, and 28.2 g of 1-bromo-4-fluoronaphthalene. The yield was 91.5%. |
With N2; bromine; In methanol; tetrachloromethane; | A. 4-Bromo-1-fluoronaphthalene To a 50 mL round-bottomed flask equipped with condenser and N2 inlet were added 3.75 mL (5.0 g, 34.25 mmol) 1-fluoronaphthalene and 10 mL carbon tetrachloride, followed by dropwise addition of 1.7 mL (5.5 g., 34.375 mmol) bromine over 3 min. The reaction was heated to 50-60 C. as HBr was evolved for 2 hours, then cooled and concentrated. The residue was dissolved in methanol and kept overnight at 0 C. After filtration with cold methanol, the product, with mp close to room temperature, was 4.62 g (60%) of a yellow oil. 1H-NMR (δ, CDCl3): 7.02 (t, J=8, 1H), 7.6-7.7 (m, 3H), 8.10 (d, J=8.5, 1H), 8.20 (d, J=8.5, 1H). | |
With N2; bromine; In methanol; tetrachloromethane; | A. 4-Bromo-1-fluoronaphthalene To a 50 mL round-bottomed flask equipped with condenser and N2 inlet were added 3.75 mL (5.0 g, 34.25 mmol) 1-fluoronaphthalene and 10 mL carbon tetrachloride, followed by dropwise addition of 1.7 mL (5.5 g., 34.375 mmol) bromine over 3 min. The reaction was heated to 50-60 C. as HBr was evolved for 2 hour, then cooled and concentrated. The residue was dissolved in methanol and kept overnight at 0 C. After filtration with cold methanol, the product, with melting point close to room temperature, was 4.62 g (60%) of a yellow oil. 1H-NMR (δ, CDCl3): 7.02 (t, J=8, 1H), 7.6-7.7 (m, 3H), 8.10 (d, J=8.5, 1H), 8.20 (d, J=8.5, 1H); GCMS (%): 224/226 (parent, Br79/Br81 100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium iodide;copper(l) iodide; trans-N,N'-dimethylcyclohexane-1,2-diamine; In 1,4-dioxane; at 110℃; for 24h;sealed tube; | <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (1 eq.), Cul (25.0 mol %), racemic trans-N,N'-dimethylcyclohexane-1,2-diamine (50 mol %), and Nal (2.5 equivalents) were added to a sealed tube, degassed, and dioxane was then added. The reaction mixture was again degassed, flushed with nitrogen and heated at 110 C. for 24 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and the solid reagents were filtered off. The filtrate was concentrated to afford a residue which was purified by column chromatography (10% ethyl acetate/hexanes) to provide the desired product. | |
With trans-N,N'-dimethyl-1,2-cyclohexyldiamine; copper(l) iodide; sodium iodide; In 1,4-dioxane; at 110℃; for 24h; | 1-Bromo-4-fluoronaphthalene (1.3 g, 5.78 mmol), CuI (275 mg, 1.44 mmol), rac-trans-N,N'- dimethylcyclohexane-l,2-diamine (424 mg, 2.89 mmol), and NaI (2.16 g, 14.4 mmol) were added to a sealed tube, degassed, and dioxane (10 mL) was then added. The reaction mixture was again degassed and flushed with nitrogen and heated at 110 0C for 24 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and the solid was filtered off. The filtrate was concentrated to obtain the crude product, which was purified by silica gel column chromatography (10% ethyl acetate/hexane as the eluant) to obtain the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In a dry 250 ml flask 3,00g (13,3 mmcl, 1 equiv.) 1-bromo-4-fluoronaphtalene is dissolved in 150 ml dry diethyl ether. The mixture is placed under inert atmosphereand cooled to -78C. Subsequently, 10 ml (0,020 mol, 1,5 equiv.) of a 2M solution of BuLi is slowly dripped in. After continuing the reaction for lh, 3,44 g (0,020 mol, 1,5 equiv.) diethylchlorophosphate is added at -78C and the mixture is allowed to warm to room temperature. After lh at room temperature the reaction is quenched using 200 ml aqueous saturated ammonium chloride and extracted three times by means ofdichloromethane. The combined organic fractions are dried using Mg504 and the volatiles are evaporated. Purification was performed using column chromatography and the compound was isolated in 88% yield as a yellow oil.‘H-NMR (300MHz, CDCI3): 5 1.31 (6H, t, J=7.2Hz, 2x CH3); 4.01-4.27 (4H, m, 2x CH2); 7.20 (1H, dxdxd, J=10.2Hz, 7.7Hz, 2.8Hz,C2H arom); 7.59-7.71 (2H, m, 2x CH arom); 8.20 (1H, dxd, J=8.OHz,6.1Hz, CHarom ); 8.25 (1H, dxd, J=8.OHz, 5.8Hz, C3H arom); 8.52 (1H,d, J=8.OHz, CHarom). ‘3C-NMR (75MHz, CDCI3): 5 16.4 (2x CH3, d, J=6.9Hz); 62.3 (2x CH2, d, J=5.8Hz); 108.6 (C2Harom, dxd, J=20.2Hz, 17.9Hz); 120.7 (CqP, dxd, J=186.9Hz, 4.6Hz);121.2 (CHarom, d, J=6.9Hz); 124.1 (Cq CqP, t, J=15.OHz); 126.6 (CHarom, t, J=3.5Hz); 126.8(CHarom); 128.5 (CHarom); 134.6 (cq CqF, dxd, J=12.7Hz, 4.6Hz); 135.5 (C3Harom, t,J=9.8Hz); 162.1 (CqF, dxd, J=259.6Hz, 4.6Hz). ‘9F-NMR (282MHz, CDCI3): 5 114.30. 31P-NMR (121MHz, CDCI3): 5 19.00. MS (ESI): m/z (%): 565 (2M-i-H, 35), 283 (M-i-H, 100).IR (cm’) vmax: 1164 (P-OEt); 1234 (P=O); 1628; 1600; 1573; 1509. Chromatography:hexanes/EtOAc 50/50 Rf= 0.25. Yield: 88%. | |
With tert.-butyl lithium; In tetrahydrofuran; at -78 - 20℃; | A solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (500 mg, 2.22 mmol) in tetrahydrofuran (5 mL) was added dropwise to stirred solution of t-BuLi (1.4 M in pentane, 3.17 mL, 4.44 mmol) in tetrahydrofuran (5 mL) at -78 C. The reaction mixture was stirred for 1 hour at-78 C, after which diethyl chlorophosphate (0.96 mL, 6.66 mmol) was added dropwise. The reaction mixture was left to warm to rt and concentrated. The residue was suspended in 2 M NaOH (50 mL) and extracted with dichloromethane (2 x 50 mL). The combined organic phases were dried over sodium sulfate, filtered and evaporated to give crude (4-fluoronaphthalen-l-yl)phosphonic acid diethyl ester (139MBT60-8C, 512 mg, 60% pure by NMR) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (500 mg, 2.22 mmol) in tetrahydrofuran (1.5 mL) was added dropwise to stirred solution of t-BuLi (1.4 M in pentane, 3.17 mL, 4.44 mmol) in tetrahydrofuran (10 mL) at-78 C. The reaction mixture was stirred for 20 minutes at-78 C, after which the temperature was raised to-40 C, and sulfur dioxide was bubbled through the mixture for 5 minutes. The resulting clear solution was left to warm to rt and concentrated. Dry ether (20 mL) was added and the resulting white solid was collected by filtration to give the crude sulfinate salt (139MBT66-A, 280 mg) as a white solid. 139MBT66-A (100 mg) was suspended in DMF (3 mL), and potassium carbonate (192 mg, 1.39 mmol) was added followed by methyl iodide (0.09 mL, 1.39 mmol). The reaction mixture was stirred at rt for 20 hours, then concentrated and re- dissolved in dichloromethane (20 mL). The organic phase was washed with 2 M NaOH (20 mL) and dried over sodium sulfate, filtered and evaporated to give crude I-fluoro-4- methanesulfonylnaphthalene (139MBT66-B, 89 mg, 86% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.7% | With piperidine;tetrakis(triphenylphosphine) palladium(0); at 80℃; for 3h; | A 30 mL Schlenk tube was replaced with Ar and <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (2.00 g, 97 mass% article, 8.62 mmol), tetrakis(triphenylphosphine)palladium (99.6 mg, 0.0862 mmol), 10.3 mL of piperidine and 2-methyl-3-butyn-2-ol (1.11 g, 98 mass% article, 12.9 mmol) were added thereto, followed by stirring of the mixture at 80C for 3 hours. The reaction mixture was cooled to room temperature, and then a saturated aqueous ammonium chloride solution was added thereto and the mixture was extracted with diethyl ether. The extract was dried over magnesium sulfate and the solvent was distilled off under reduced pressure by an evaporator. The crude reaction product was purified by column chromatography (Hexane/AcOEt=100/0->1/5) using silica gel to give 1.88 g of dimethylhydroxymethyl-4-fluoro-1-naphthylacetylene as a yellow liquid (yield: 95.7%). 1H-NMR (300 MHz, CDCl3) δ: 8.28-8.25 (m, 1H), 8.12-8.09 (m, 1H), 7.65-7.54 (m, 3H), 7.11-7.05 (m, 1H), 2.19 (brs, 1H), 1.72 (s, 6H) [MS] EI (m/z): 228(M+), CI (m/z): 229(MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium t-butanolate;palladium diacetate; CyJohnPhos; In toluene; at 80℃; | [0832] A first intermediate compound, 1-(4-Fluoro-naphthalen-1-yl)-piperazine, was produced as follows: A mixture of dicyclohexylphosphino biphenyl (0.155 g, 0.444 mmol, 0.1 mmol) and palladium acetate (0.099 g, 0.444 mmol, 0.1 equiv) in dry toluene (15 mL) was bubbled with N2 gas for two hours. To the resultant clear solution was added 1-bromo-4-fluoro naphthalene (1.0 g, 4.44 mmol, 1.0 equiv) followed by 1-Boc-piperazine (1.0 g, 5.33 mmol, 1.2 equiv). To this mixture was added NaOtBu (0.600 g, 6.22 mmol, 1.4 equiv) and the reaction mixture was stirred at 80 C. overnight. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was taken up in CH2Cl2, filtered through a celite bed, and then rinsed with CH2Cl2. The combined filtrates were concentrated and purified by column chromatography on silica (20% EtOAc in hexane). 4-(4-Fluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester (1.4 g, impure) was obtained as a dark viscous liquid, which was used in the next step without further purification. 1H NMR: (400 MHz, CDCl3) δ 8.25 (m, 1H), 8.05 (m, 1H), 7.55 (m, 2H), 7.05-6.80 (m, 2H), 4.00 (br s, 4H), 3.00 (br s, 4H), 1.45(s, 9H). MS: ES+ 331.13 (M+H)+ (Exact mass: 330.17). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; hexane; at -78 - 20℃; for 1.16667h; | Reference Example 73 To a mixture of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (1.57 g) and tetrahydrofuran (30 mL) was added at -78C a 1.6 Mn - butyllithium - hexane solution (4.8 mL). The mixture was stirred for 20 minutes, and then added to a mixture of ethyl trifluoroacetate (1.7 mL) and tetrahydrofuran (20 mL) at the same temperature. After stirring for 20 minutes, the mixture was stirred for 30 minutes with elevating to room temperature. The reactant was poured into brine and extracted with ethyl acetate. The extracts were washed with brine, dried and concentrated. The obtained residue was purified by silica gel column chromatography to obtain 2,2,2-trifluoro-1-(4-fluoro-1-naphthyl)ethanone (865 mg). 1H-NMR (300 MHz, CDCl3) δ: 7.25 (1H, dd, J=9.6 and 8.4 Hz), 7.69 (1H, ddd, J=8.4, 6.9 and 1.2 Hz), 7.79 (1H, ddd, J=8.4, 6.9 and 1.8 Hz), 8.21-8.27 (2H, m), 8.95-8.99 (1H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; N2; In tetrahydrofuran; hexane; | B. 4-Fluoronaphthalene-1-boronic Acid To a 250 mL three-necked round-bottomed flask equipped with septum and N2 inlet were added 4.62 g (20.53 mmol) 4-bromo-1-fluoronaphthalene and 100 mL dry tetrahydrofuran. The solution was cooled to -70 C., and 15.4 mL (24.64 mmol) of a 1.6M solution of butyl lithium in hexane was added dropwise over 5 min. The reaction was stirred at -70 C. for 10 min, then 4.2 mL (3.59 g, 24.64 mmol) triethyl borate was added, and the reaction stirred at -70 C. for 20 min and warmed to room temperature. After stirring overnight at room temperature, the reaction was quenched with saturated aqueous ammonium chloride solution, acidified with 1N hydrochloric acid, and extracted into ethyl acetate (twice). The combined organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was triturated with hexane to give an off-white powder, 1.97 g (51%), as a mixture of monoaryl and diaryl boronic acids. 1H-NMR (delta, CDCl3): 7.2-7.4 (m, 1H), 7.5-7.7 (m, 3H), 8.0-8.5 (m, 1H), 8.5 and 9.2 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With hydrogenchloride; n-butyllithium; In tetrahydrofuran; water; ethyl acetate; | 1. Ethyl 2-(4-fluoronaphthyl)-2-oxoacetate A solution of n-butyllithium (2.5 M in THF, 20 mL, 50 mmol) was cooled to -78 C., and a solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (11.25 g, 50 mmol) in THF (40 mL) was added slowly and the mixture was stirred for 1 hour. The reaction mixture was warmed to -20 C., then added to a solution of diethyl oxalate (29.2 g,200 mmol) in THF (40 mL) at -78 C. After slowly warming-up to room temperature, EtOAc (100 mL), 10% HCl (50 mL) and water (50 mL) were added and the phases were separated. The aqueous layer was extracted with EtOAc (2*100 mL), and the organic layers were combined, washed with brine (50 mL), and dried over Na2SO4. After evaporating the solvent and the excess diethyl oxalate under high vacuum, the residue was purified by flash column chromatography (1:1 DCM:hexane) to give the title compound (9.4 g, 76% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (9.13 (d, J=8.6 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 8.01 (dd, J=8.2, 5.4 Hz, 1H), 7.76 (t, J=7.2 Hz, 1H), 7.67 (t, J=8.1 Hz, 1H), 7.21 (t, J=8.5 Hz, 1H), 4.49 (q, J=7.1 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; sodium carbonate;tetrakis(triphenylphosphine)palladium (0); In tetrahydrofuran; benzene; | A. Preparation of (17) where R1 is Isopropyl, R2 is Hydrogen, and R3 is 4-Fluoro-1-naphthyl A stirred solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (4.95 g) in 100 mL tetrahydrofuran was cooled to -80 C., stirred and 2.5M n-butyllithium (10 mL) was added dropwise. The mixture was stirred for 30 minutes, then trimethoxyborane (3 mL) added, the mixture stirred for 1 hour, then allowed to warm to room temperature, and solvent removed under reduced pressure. To this residue was added benzene (100 mL), 4-chloro-6-isopropyl-2-(methylthio)pyrimidine (4.04 g), tetrakis(triphenylphosphine)palladium(0) (500 mg), and sodium carbonate (20 mL of 2M), was heated to reflux (about 80 to 90 C.) for 14 hours. The mixture was filtered, and solvent was removed under reduced pressure. The residue was chromatographed on silica gel, eluding with 2% ethyl acetate/hexane, to give impure 4-(4-fluoronaphth-1-yl)-6-isopropyl-2-(methylthio)pyrimidine (4.87 g), which was used in the next reaction with no further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; | A. Preparation of I where R1 is n-Propyl, R2 is Hydrogen, R1 is 4-Fluoronaphth-1-yl, and R4 and R5 are Hydrogen To a stirred solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (0.5 g) in 10 mL of tetrahydrofuran at -78 C. under nitrogen was added n-butyllithium (1.6M, 1.53 mL) dropwise. The solution was allowed to stir for 5 minutes, then trimethoxyborane (0.33 mL) was added dropwise. The solution was allowed to warm to room temperature and the solvent removed under reduced pressure to give a solid, dimethoxy-(4-fluoronaphth-1-yl)borane, a compound of formula (7). | |
With n-butyllithium; In tetrahydrofuran; | A. Preparation of I where R1 is n-Propyl, R2 is Hydrogen, R3 is 4-Fluoronaphth-1-yl, and R4 and R5 are Hydrogen To a stirred solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (0.5 g) in 10 mL of tetrahydrofuran at -78 C. under nitrogen was added n-butyllithium (1.6M, 1.53 mL) dropwise. The solution was allowed to stir for 5 minutes, then trimethoxyborane (0.33 mL) was added dropwise. The solution was allowed to warm to room temperature and the solvent removed under reduced pressure to give a solid, dimethoxy-(4-fluoronaphth-1-yl)borane, a compound of formula (7). | |
To a stirred solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (0.5 g) in 10 ml of tetrahydrofuran at -78C under nitrogen was added n-butyllithium (1.6M, 1.53 ml) dropwise. The solution was allowed to stir for 5 minutes, then trimethoxyborane (0.33 ml) was added dropwise. The solution was allowed to warm to room temperature and the solvent removed under reduced pressure to give a solid, dimethoxy-(4-fluoronaphth-1-yl)borane, a compound of formula (7). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | Example 14 Cis and trans 1-(4-fluoro-1-naphthalenyl)-4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanol These compounds were prepared from 4-fluoro-1-bromonaphthalene (12 mmole) and 4-[4-(phenylmethyl)-1-piperazinyl]cyclohexanone (10 mmole) by the method described in Example 13 which after separation as described gave the cis isomer (12%, mp: 205-207 C.). Calc'd for C27 H31 FN2 O.0.4H2 O: C, 76.17%; H, 7.53%; N, 6.59%; H2 O, 1.69%. Found: C, 76.03%; H, 7.36%; N, 6.68%; H2 O, 0.94% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; In tetrahydrofuran; hexane; | B. 4-Fluoronaphthalene-1-boronic acid To a 250 mL three-necked round-bottomed flask equipped with septum and N2 (nitrogen) inlet were added 4.62 g (20.53 mmol) 4-bromo-1-fluoronaphthalene and 100 mL dry tetrahydrofuran. The solution was cooled to -70 C., and 15.4 mL (24.64 mmol) of a 1.6 M solution of butyl lithium in hexane was added dropwise over 5 min. The reaction was stirred at -70 C. for 10 min, then 4.2 mL (3.59 g, 24.64 mmol) triethyl borate was added, and the reaction stirred at -70 C. for 20 min and warmed to room temperature. After stirring overnight at room temperature, the reaction was quenched with saturated aqueous ammonium chloride solution, acidified with 1 N hydrochloric acid, and extracted into ethyl acetate (twice). The combined organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was triturated with hexane to give an off-white powder, 1.97 g (51%), as a mixture of monoaryl and diaryl boronic acids. 1H-NMR (delta, CDCl3): 7.2-7.4 (m, 1H), 7.5-7.7 (m, 3H), 8.0-8.5 (m, 1H), 8.5 and 9.2 (m, 1H); APCl (-) (%): 189 (parent-1, 60). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 20 - 80℃; for 17.0167h; | 4-fluoro-N-[4-(methylthio)phenvϖnaphthalen-1 -amine (ST3455).; A dried flask was purged with argon and charged with (+/-) BINAP (160 mg, 0,25 mmol) and capped with a rubber septum. The flask was purged with argon and toluene (24 ml) was added. The mixture was heated to 80 C with stirring until the BINAP dissolved. The solution was cooled to room temperature, the septum was removed, and palladium acetate (40 mg, 0,17 mmol) was added. The flask was recapped with the septum and then purged with argon. The mixture was stirred at room temperature for 1 min, the 4-(methylthio)aniline (1 ,12 g, 8.04 mmol) dissolved in toluene (3 ml) and <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (1,50 g, 6,7 mmol) were added, the septum was removed, and cesium carbonate (3,06 g, 9,38 mmol) was added. Additional toluene (18 ml) was added, then the flask was recapped with the septum, and purged with argon again. The mixture was heated to 80C under stirring for 17h. The mixture was cooled to room temperature, diluted with ether, filtered, and concentrated in vacuo. The crude product (2,85 g) was then purified by column chromatography (chloroform/petroleum ether 1 :1 as eluent) to obtain 1 ,79 g (94%) of pure ST3455; p.f. 71-72 0C (n-hexane); IR: v 3337 (NH) cm"1; 1H-NMR (DMSOd6): δ 2,44 (s, 3H, CH3), 6,93 (d, 2H, J0 = 8,7 Hz, benzene EPO <DP n="56"/>C3-H and C5-H), 7,20-7,33 (m, 4H, benzene C2-H and C3-H, naphthalene C2-H and C3-H), 7,63-7,71 (m, 2H, naphthalene C6-H and C7-H), 8,07 and 8,18 (2m,2H, naphthalene C5-H and C8-H), 8,21 (s broad, 1 H1NH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 20 - 80℃; for 5.76667h; | Step i - preparation of: 4-fluoro-N-(4-fluorophenvϖnaphthalen-1 -amine ( ST35981; A dried flask was purged with argon and charged with (+/-) BINAP (160 mg, 0,25 mmol) and capped with a rubber septum. The flask was purged with argon and toluene (24 ml) was added. The mixture was heated to 80 0C with stirring until the BINAP dissolved. The solution was cooled to room temperature, the septum was removed, and palladium acetate (40 mg, 0,17 mmol) was added. The flask was recapped with the septum and then purged with argon. The mixture was stirred at room temperature for 1 min, the 4-fluoroaniline (890 mg, 8.04 mmol) dissolved in toluene (3 ml) and <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (1 ,50 g, 6,7 mmol) were added, the septum was removed, and cesium carbonate (3,06 g, 9,38 mmol) EPO <DP n="53"/>was added. Additional toluene (18 ml) was added, then the flask was recapped with the septum, and purged with argon again. The mixture was heated to 800C under stirring for 5h and 45 min. The mixture was cooled to room temperature, diluted with ether, filtered, and concentrated in vacuo. The crude product (2,31 g) was then purified by column chromatography (Chloroform as eluent) to obtain 1.87 g (91%) of pure ST3598. p.f. 62-64 0C (not crystallized); IR: v 3395 cmJ (NH); 1H- NMR (CDCI3): δ 5,55 (s broad, 1 H, NH), 6,86-6,90 (m, 2H, benzene H), 6,98-7,03 (m, 2H, benzene H), 7,11-7,17 (m, 1H, naphthalene C2-H), 7,24 (m, 1H, naphthalene C3-H), 7,57-7,66 (m, 2H, naphthalene C6-H and C7-H), 8,05 and 8,20 (2m, 2H, naphthalene C5-H and C8-H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 68 (1S)-1-{2-[(2R)-4-(4-Fluoro-1-naphthyl)-2-methylpiperazinyl]ethyl}-3,4-dihydro-1H-2-benzopyran-6-carboxamide Prepared from 1-fluoro-4-bromonaphthalene and (2R)-methylpiperazine. M+H=448. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 110℃; for 16h; | To a mixture of l-bromo-4-fluoronaphthalene (108 mg, 0.48 mmol) in toluene (1 ml) was added 3-chloroaniline (74 mg, 62 μl, 0.53 mmol), Pd2(dibenzylideneacetone)3 (1 mg, 0.001 mmol), BINAP (2 mg, 0.004 mmol), and sodium tert-butoxide (65 mg, 0.68 mmol). The reaction was heated at 1100C for 16 h. The reaction was cooled to 200C, diluted with ethyl acetate (15 ml), and this was washed with water (2 x 10 ml), and saturated aqueous NaCl (5 ml), dried (Na2SO4), and concentrated. The crude material was purified by preparative-TLC (10% ethyl acetate: hexane), followed by preparative-TLC (33% CH2Cl2: hexane) to give the desired product (41 mg, 31%) as an off-clear viscous liquid. 1H NMR (CD3OD) δ ppm: 6.71-6.83 (m, 3H), 7.07-7.18 (m, 2H), 7.21-7.35 (m, IH),7.54-7.63 (m, 2H), 8.05-8.12 (m, 2H). HPLC: 100% at 2.100 minutes; Sunfire C18 4.6 x 50 mm; 10-90% methanol: water with 0.1% TFA; Gradient time = 2 min; 3.5 ml/ min; 254 nm. MS = 272 M+H+. |
31% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 110℃; for 16h; | To a mixture of l-bromo-4-fluoronaphthalene (108 mg, 0.48 mmol) in toluene (1 ml) was added 3-chloroaniline (74 mg, 62 μl, 0.53 mmol), Pd2(dibenzylideneacetone)3 (1 mg, 0.001 mmol), BINAP (2 mg, 0.004 mmol), and sodium tert-butoxide (65 mg, 0.68 mmol). The reaction was heated at 1100C for 16 h. The reaction was cooled to 200C, diluted with ethyl acetate (15 ml), and this was washed with water (2 x 10 ml), and saturated aqueous NaCl (5 ml), dried (Na2SO4), and concentrated. The crude material was purified by preparative-TLC (10% ethyl acetate: hexane), followed by preparative-TLC (33% CH2Cl2: hexane) to give the desired product (41 mg, 31%) as an off-clear viscous liquid. 1H NMR (CD3OD) δ ppm: 6.71-6.83 (m, 3H), 7.07-7.18 (m, 2H), 7.21-7.35 (m, IH),7.54-7.63 (m, 2H), 8.05-8.12 (m, 2H). HPLC: 100% at 2.100 minutes; Sunfire C18 4.6 x 50 mm; 10-90% methanol: water with 0.1% TFA; Gradient time = 2 min; 3.5 ml/ min; 254 nm. MS = 272 M+H+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of l-bromo-4-fiuoronaphthalene (229 mg, 1.02 mmol) In THF (6 mL) at -78C was added BuLi (2.5 M in hexanes, 0.434 mL, 1.086 mmol), then the solution was stirred for one hour. A solution of /-butyl (i?)-4-[2-(4-methoxyphenyl)-l~propylethan-2-one-l- yl]benzoate (prepared using the procedure for INTERMEDIATE 4, 250 mg, 0.678 mmol) in THF (2 mL) was added and the solution was stirred for an additional hour. The solution was quenched with saturated NH4Cl (aq), then diluted with EtOAc (50 mL). The organic layer was separated, washed with water then brine, dried over MgSO4, filtered, then concentrated. The residue was purified by silica gel chromatography eluting with 0-20% EtOAc/hexanes to afford the title compound. LCl 1.30 min. [M+H-H20]+ 497. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
PREPARATION 6; Preparation of Compounds of Formula (17); A. Preparation of (17) where R1 is Isopropyl, R2 is Hydrogen, and R3 is 4-Fluoro-1-naphthyl; A stirred solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (4.95 g) in 100 ml tetrahydrofuran was cooled to -80C, stirred and 2.5M n-butyllithium (10 ml) was added dropwise. The mixture was stirred for 30 minutes, then trimethoxyborane (3 ml) added, the mixture stirred for 1 hour, then allowed to warm to room temperature, and solvent removed under reduced pressure. To this residue was added benzene (100 ml), 4-chloro-6-isopropyl-2-(methylthio)pyrimidine (4.04 g), tetrakis(triphenylphosphine)palladium(0) (500.mg), and sodium carbonate (20 ml of 2M), was heated to reflux (about 80 to 90C) for 14 hours. The mixture was filtered, and solvent was removed under reduced pressure. The residue was chromatographed on silica gel, eluting with 2% ethyl acetate/hexane, to give impure 4-(4-fluoronaphth-1-yl)-6-isopropyl-2-(methylthio)pyrimidine (4.87 g), which was used in the next reaction with no further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Step 1: 4-Bromo- 1 -fluoro-2-naphthoic acidA solution of 2,2,6,6-tetramethylpiperidine (6.85 g, 8.25 ml, 48.0 mmol) in THF (70.0 ml) was cooled to -78C under nitrogen atmosphere and n-butyl lithium (29.9 ml, 47.9 mmol) was added dropwise to the reaction mixture. The reaction was stirred at -78C for 30 mm and a solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (10 g, 43.5 mmol) in THF (20 ml) was added dropwise at -78C. The mixture was stirred for 1 h and solid CO2 was added at the same temperature. The reaction was stirred for 2 h and treated with 20% aqueous ammonium chloride solution. The mixture was allowed to warm to room temperature, was acidified by a solution of HC1 iN and was diluted with EtOAc. The aqueous layer was extracted two times with EtOAc. The combined organic layers were dried over Na2504, filtered and the solvent was removed into vacuo. The precipitate was taken up in CH2C12 and filtered to provide the title compound (8.6 g, 74%) as white solid. MS (mle): 267.2, 269.2 (M+H) | |
74% | Step 1: 4-Bromo-1-fluoro-2-naphthoic acid A solution of 2,2,6,6-tetramethylpiperidine (6.85 g, 8.25 ml, 48.0 mmol) in THF (70.0 ml) was cooled to -78 C. under nitrogen atmosphere and n-butyl lithium (29.9 ml, 47.9 mmol) was added dropwise to the reaction mixture. The reaction was stirred at -78 C. for 30 min and a solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (10 g, 43.5 mmol) in THF (20 ml) was added dropwise at -78 C. The mixture was stirred for 1 h and solid CO2 was added at the same temperature. The reaction was stirred for 2 h and treated with 20% aqueous ammonium chloride solution. The mixture was allowed to warm to room temperature, was acidified by a solution of HCl 1N and was diluted with EtOAc. The aqueous layer was extracted two times with EtOAc. The combined organic layers were dried over Na2SO4, filtered and the solvent was removed into vacuo. The precipitate was taken up in CH2Cl2 and filtered to provide the title compound (8.6 g, 74%) as white solid. MS (m/e): 267.2, 269.2 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.4% | With palladium diacetate; sodium carbonate; In N,N-dimethyl acetamide; at 120℃; for 12h;Inert atmosphere; | To a solution of <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> 11 (0.5 g,2.22 mmol) and K4Fe(CN)6 (0.23 g, 0.62 mmol) in DMAc (20 mL)was added anhydrous Na2CO3 (0.24 g, 1.69 mmol) and Pd(OAc)2(0.02 g, 0.1 mmol). The mixturewas heated to 120 C for 12 h undernitrogen protection, then the reaction mixture was cooled to roomtemperature. Water (50 mL) was added and then the mixture wasextracted with ethyl acetate (50 mL 3), and washed with brine(100 mL 2). The organic layer was dried and concentrated to givethe intermediate 12 (0.34 g) as off-white solid in 88.4% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69%Spectr. | With tetrakis(triphenylphosphine) palladium(0); at 150℃; for 0.5h; | The coupling reaction of 1,1,2-trifluorovinyl chloride chloride and <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> prepared in the same manner as in Example 9 was carried out in the presence of 1 mol% of Pd (PPh 3) 4 at 150 C. For 30 minutes. The coupled product was confirmed and quantified by 19 F-NMR (yield 69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere; | General procedure: A mixture of 3a-3g (0.1 mol for 3a-3e and 3g; 0.4 molfor 3f) and CuCN (26.87 g, 0.3 mol for 3a-3e and 3g; 21.49g, 0.24 mol for 3f) in DMF (300 mL) were stirred at 130C in N2 atmosphere for 12 h, when TLC analysis indicated completion of reaction. On cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (900 mL) and the resulting mixture was further stirred for 1 h and filtered off. The filtrate was washed with 5% brine (500 mL 5), dried (Na2SO4) and evaporated on a rotary evaporator to afford a black oil, which was purified by column chromatography to afford the pureproduct 4a-4g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.2% | With n-butyllithium; In tetrahydrofuran; at -78 - 20℃; for 0.5h; | In a 500 mL three-necked flask, 1-bromo-4-fluoronaphthalene (27.9 g, 0.124 mol) was dissolved in anhydrous tetrahydrofuran (200.0 mL), triisopropyl borate (26.8 g, 0.142 mol) was added, cooled to -78 C, n-butyllithium (9.5 g, 0.149 mol) was added at -78 C for 0.5 h and then returned to room temperature. The reaction was quenched by adding saturated aqueous ammonium chloride solution. The pH was strongly acidic and extracted with ethyl acetate (200.0 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was beaten with n-hexane and filtered to obtain 21.2 g of a 4-fluoronaphthalene-1-boronic acid solid in a yield of 90.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With n-butyllithium; In tetrahydrofuran; at -78 - 20℃; for 0.5h; | In a 500 mL three-necked flask, 1-bromo-4-fluoronaphthalene (28.1 g, 0.125 mol) was dissolved in anhydrous tetrahydrofuran (200.0 mL), tri-n-butyl borate (35.9 g, 0.156 mol) was added, cooled to -78 C, n-butyllithium (10.4 g, 0.162 mol) was added to the solution at -78 C for 0.5 h and then returned to room temperature. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution. The pH was strongly acidic and extracted with ethyl acetate (200.0 mL × 3). The combined organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was beaten with n-hexane and filtered to give 21.3 g of 4-fluoronaphthalene-1-boronic acid in 90% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.6% | With n-butyllithium; In tetrahydrofuran; at -78 - 20℃; for 1h; | In a 500 mL three-necked flask, 1-bromo-4-fluoronaphthalene (24.6 g, 0.109 mol) was dissolved in anhydrous tetrahydrofuran (200.0 mL), trimethyl borate (12.5 g, 0.120 mol) was added, cooled to -78 C, n-butyllithium (7.7 g, 0.120mol). After 1 h at -78 C, the reaction was allowed to recover to room temperature. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution. The pH was strongly acidic and extracted with ethyl acetate (200.0 mL × 3). The combined organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was slurried with n-hexane and filtered to obtain 18.4 g of a 4-fluoronaphthalene-1-boronic acid solid in a yield of 88.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; palladium diacetate; XPhos; In toluene; at 90℃; for 16h; | Palladium (II) acetate (0.091 g, 0.41 mmol) was added to a mixture of methyl 3-amino-5-morpholino-2-nitrobenzoate (1.00 g, 4.00 mmol), <strong>[341-41-3]1-bromo-4-fluoronaphthalene</strong> (0.880 g, 4.00 mmol), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (0.578 g, 1.00 mmol), and potassium phosphate (2.143 g, 10.00 mmol) in toluene (4 mL). The resultant was degassed and stirred at 90 C. for 16 hours. The reaction mixture was cooled to room temperature and dry loaded onto silica gel and purified via column chromatography eluting with 0 to 100% Ethyl acetate in Hexanes to afford methyl 3-((4-fluoronaphthalen-1-yl)amino)-5-morpholino-2-nitrobenzoate. ES/MS m/z=426.2 (M+H)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 70℃; for 5.0h; | To a solution of 1-bromo-4-fluoronaphthalene (2.25 g, 10 mmoL) in 1, 4-dioxane /H2O (80 mL/20mL) was added 4, 4, 5, 5-tetramethyl-2- (1, 4-dioxaspiro [4.5] dec-7-en-8-yl) -1, 3, 2-dioxaborolane (2.66 g, 10 mmol) , Pd (dppf) Cl2(731 mg, 1.0 mmol) and Cs2CO3(4.88 g, 1.5 mmol) and the mixture was heated at 70 for 5 hours. Then evaporated the solvent under reduced pressure and the residue was purified by column chromatography (PE: EA=5: 1) to give product as an oil (2.1 g in 74%yield) . [M+H]+=285 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.9% | With n-butyllithium; In tetrahydrofuran; hexane; at -78 - 20℃; for 1h;Inert atmosphere; | General procedure: To a solution of 1-bromonaphthalene (8.28 g, 40.0 mmol) and chlorodimethylsilane (5.20 mL,47.9 mmol) in THF (100 mL) was added n-butyllithium (1.65 M in n-hexane, 27.0 mL, 44.6 mmol)at -78 C. After warming to room temperature, the mixture was stirred for 1 h at the sametemperature. To the mixture was added aqueous phosphate buffer (pH 7.4, ca. 30 mL) at roomtemperature and extracted with n-hexane (ca. 30 mL × 3). The combined organic extract was driedover Na2SO4 and after filtration, the filtrate was concentrated under reduced pressure. The residuewas purified by silica-gel column chromatography (n-hexane) to give 3a (7.21 g, 38.7 mmol, 96.7%)as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.6% | To a solution of 1-bromo-4-fluoro-naphthalene (1.0 g, 4.4 mmol) in THF (10.0 mL) was added LDA (2 M, 3.3 mL) at -78C under N2. The mixture was stirred at -78 C for 1h. Then DMF (356 mg, 4.8 mmol, 375.7 uL) was added. The mixture was stirred at -78C for 2h. The reaction mixture was quenched by addition NH4C1 (10.0 mL), extracted with ethyl acetate (10.0 mL x 3). The combined organic layers were washed with brine (10.0 mL x 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (Si02, Petroleum ether / Ethyl acetate = 10/1) to afford 4-bromo-1-fluoro- 2-naphthaldehyde (1.0 g, 3.36 mmol, 75.6% yield). (DMSO-d6, 400MHz): 5 10.40 (s, 1H), 8.35 (d, J 8.3 Hz, 1H), 8.24 (d, J 8.6 Hz, 1H), 8.08 (d, J= 6.1 Hz, 1H), 8.00 (t, J= 7.7 Hz, 1H), 7.92 - 7.85 (m, 1H). |
Tags: 341-41-3 synthesis path| 341-41-3 SDS| 341-41-3 COA| 341-41-3 purity| 341-41-3 application| 341-41-3 NMR| 341-41-3 COA| 341-41-3 structure
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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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