Structure of 186663-74-1
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CAS No. : | 186663-74-1 |
Formula : | C11H15NO3 |
M.W : | 209.24 |
SMILES Code : | O=C(OC(C)(C)C)NC1=CC=CC=C1O |
MDL No. : | MFCD06411300 |
InChI Key : | UQLYDIDMLDTUDL-UHFFFAOYSA-N |
Pubchem ID : | 4935485 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.36 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 58.71 |
TPSA ? Topological Polar Surface Area: Calculated from | 58.56 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 2.29 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.19 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.98 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.5 |
Solubility | 0.664 mg/ml ; 0.00317 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -2.97 |
Solubility | 0.224 mg/ml ; 0.00107 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -2.78 |
Solubility | 0.347 mg/ml ; 0.00166 mol/l |
Class? Solubility class: Log S scale | Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg | High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg | Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) | No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) | Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) | No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) | No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.08 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from | 0.0 |
Ghose? Ghose filter: implemented from | None |
Veber? Veber (GSK) filter: implemented from | 0.0 |
Egan? Egan (Pharmacia) filter: implemented from | 0.0 |
Muegge? Muegge (Bayer) filter: implemented from | 0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat | 0.55 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from | No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 2.11 |
* 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 |
---|---|---|
99% | With iron(III) trifluoromethanesulfonate; In neat (no solvent); at 20℃; for 0.0833333h;Green chemistry; | General procedure: Fe(OTf)3 (1 mol%) was added to a magnetically stirred mixture of anamine (1 mmol) and Boc2O (1 mmol) at room temperature. The mixturewas stirred until completion of the reaction (TLC), then diluted withEtOAc and washed with water. The organic layer was dried overanhydrous MgSO4, then the solvent was distillated off under vacuum toyield the highly pure N-Boc derivatives |
99% | at 20℃; for 0.216667h;Ionic liquid; | To the ionic liquid [TPA][Pro] (1 mL) was added amine (1-14; Table-1) (1 mmol) and di-tert-butyl dicarbonate (1.2 mmol). The reaction was stirred at room temperature for an appropriate time (Table-1). After completion of the reaction as monitored by TLC, water was added to the reaction mixture and the product was extracted into ethyl acetate (3 × 20 mL). The combined organic layer was washed with brine solution and concentrated under reduced pressure to give crude product, which was purified over silica gel column to afford corresponding N-tert-butylcarbamate. The ionic liquid [TPA][Pro] in aqueous solution was recovered by removing water under reduced pressure and dried. The recovered ionic liquid was reused for five times without loss of its activity. Finally, all the compounds confirmed by their m.p.?s, IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis wherever needed. |
97% | In tetrahydrofuran; for 16h; | 2-Amino phenol (6 g, 55 mmol) was dissolved in 60 mL of THF. (Boc)20 (12 g, 55 mmol) was added to the above mixture and stirred for 16 h. The mixture was concentrated under vacuum to get a gummy mass. Gummy mass was precipitated using 20% MTBE/Hexane. Precipitated solid was filtered and washed with hexane to afford tert-butyl (2- hydroxyphenyl)carbamate (1 1.2 g, 97% yield) |
96% | With guanidine hydrochloride; In ethanol; at 35 - 40℃; for 0.25h; | General procedure: Amine (1 mmol) was added to a magnetically stirred solution of guanidine hydrochloride (15 mol%) and di-tert-butyl dicarbonate (1.2 mmol) in EtOH (1 mL), at 35-40C and stirred for appropriate time (Table 1). After completion of the reaction (followed by TLC or GC), EtOH was evaporated under vacuum and the residue either was washed with water to remove the catalyst or was dissolved in CH2Cl2 (or EtOAc) and filtered off to separate out the catalyst. Evaporation of the organic solvent (if used in work up) gives almost a pure product. In the cases of using an excess (Boc)2O the product was washed with petroleum ether or hexane to recover the residual (Boc)2O. If necessary, the product was further purified either by crystallization (hexane and dichloromethane, or diethyl ether and petroleum ether) or silica gel column chromatography using EtOAc-hexane (1: 6) as eluent. |
95% | With iron oxide; In ethanol; at 20℃; for 0.5h;Green chemistry; | General procedure: A round-bottom flask (10 mL), which contains EtOH(5 mL), was charged with a solution of diboc (1-2 mmol),nano-Fe3O4 (3 mol%, 0.007 g) and the amine (1 mmol). The mixture was stirred at room temperature for the appropriate time (Table 3). After completion of the reaction, the catalyst was collected by a magnet and separated from the solution of product and the remaining starting materials.After drying and evaporation of the solvent, the resulting solid was recrystallized from n-hexane or ethyl acetate(5 mL) to give the pure product. The recovered catalyst was washed with EtOH, dried and reused for the next run. The catalyst was recovered and reused for six times without any significant changes in the yield and the reaction time. |
95% | For the N-boc protection of amines, to solution of diboc (1 mmol) in ethanol (5 ml) was added {K*18-crown-6]Br3}n (0.001 mmol). The solution was stirred at room temperature for 1 min. The amine (1 mmol) was then added and solution as stirred at room temperature for an appropriate time (table 1). After completion of the reaction, the solvent was removed by water bath distillation. To the residue was added ethyl acetate (5 ml) and the mixture was filtered (the catalyst is insoluble in n-hexane and ethyl acetate). The solid was washed with ethyl acetate ()10 ml*2) amd combined filtrates were reduced to dryness to yield the pure products. | |
94% | at 30℃; for 16h;Inert atmosphere; | General procedure: The corresponding aminophenol (1 mmol) and Boc2O (1 mmol) were stirred at 30 C for 16 h undersolvent free conditions. The crude reaction mixture was purified by FC eluting with hexane/EtOAc(8:2). |
93% | at 20℃; for 0.5h;Green chemistry; | General procedure: To (Boc)2O (1.0 mmol), was added an amine (1.0 mmol)and the mixture was stirred at room temperature for the time indicated in Table 1. The progress of the reaction was monitored by TLC. In most cases, the BOC protected product was found to be sufficiently pure and did not require any further purification. In some cases the product was purified by silica gel column chromatography (1:2; EtOAc/ Petrolium ether).All products were characterized by IR, 1H NMR and their physical properties. |
92% | With 1,3-disulfonic acid imidazolium hydrogen sulfate; In neat (no solvent); at 20℃; for 0.133333h;Green chemistry; | General procedure: Amine (1 mmol) was added to the mixture of (Boc)2O (1 mmol) and DSIMHS (6.5 mg, ~ 0.02 mmol) with constant stirring at room temperature under solvent-free conditions. After completion of the reaction (monitored by TLC), ethyl acetate (3 × 5 mL) was added to the reaction mixture and the catalyst was decanted and washed with ethyl acetate (2 × 5 mL) and dried. The product was purified by column chromatography, using ethyl acetate-petroleum ether (2:8) eluent. |
87.7% | In tetrahydrofuran;Inert atmosphere; | To a stirred solution of 2-aminophenol (5.0 g, 45.87 mmol) in anhydrous THF(50 mL) was added di-t-butyl dicarbonate (10.5 g, 48.17 mmol) dropwise, and thesolution was stirred overnight under argon atmosphere. Then the reaction mixture wasdiluted with ethyl acetate (80 mL) and washed with saturated brine (60 mL), water(60 mL×2), and then dried over anhydrous magnesium sulfate. The crude product waspurified by silica gel column chromatography (petroleum ether/ethyl acetate = 20:1)to afford the title compound as a white solid (8.4 g, 87.7%); mp 148-150 C; 1H NMR(400 MHz, Acetone-d6) delta (ppm) 8.86 (s, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.63 (brs, 1H),6.89-6.82 (m, 3H), 1.51 (s, 9H); HRMS (ESI): m/z, Calcd. for C6H8ON [M+H-Boc]+:110.0600, Found 110.0602. |
80% | In tetrahydrofuran; at 20℃; for 15h;Inert atmosphere; | Di-tert-butyldicarbonate (11 mmol) was added to a stirred solution of 2-aminophenol (10 mmol) in dry THF (15 mL). The reaction mixture was stirred for 15 hours at room temperature (RT) under a nitrogen atmosphere. Then, the solvent was evaporated under vacuum and the resulting reaction mixture was washed with pentane (20 mL) and dissolved into diethyl ether (30 mL). Diethyl ether portion was washed with diluted HCl (10 mL), then dried over Na2SO4 and filtered. On evaporation under vacuum the targeted compound was obtained as a white solid (80%). 1H NMR data were: deltaH (500 MHz; CDCl3) 8.17 (1H, s, H-N), 7.11-6.81 (4H, m, ArH), and 1.52 (9H, s, CH3); and deltac (500 MHz; CDCl3) 155.0 (C=O), 147.2 (C), 125.8 (C), 121.6 (CH), 120.7 (CH), 118.6 (CH), 82.0 (C), and 28.35 (CH3). |
42.4% | With triethylamine; In tetrahydrofuran; water; | To the solution of 2-aminophenol (1) (4?g, 36.6?mmol) in 60?mL THF-water (1:1 v/v) triethylamine (Et3N) (9.8?mL, 44.1?mmol) was added. Then, BOC anhydride (8.4?mL, 36.6?mmol) was added and stirred overnight. The reaction mixture was diluted with water and subsequently extracted with ethyl acetate. The organic layer was dried over Na2SO4, and the solvent was evaporated. The crude mixture was purified via column chromatography (hexane:EtOAc, 3:1) to get desired product in a light orange color. Yield?=?3?g, (42.4%). 1H-NMR (DMSO-d6, 300?MHz, delta in ppm): 9.74 (1H, s, Ar-OH), 7.79 (1H, d, -NHCCH), 7.60-7.57 (1H, d, -OHCCH), 6.87-6.74 (1H, m, -CHCHCH-), 1.46 (9H, s, -CH3). |
In dichloromethane; | (a) To a solution of 2-aminophenol (2.84 g) in dichloromethane (120 ml) was added di-tert-butyl dicarbonate (6.55 g). The mixture was stirred at room temperature for 18 hours. The mixture was partitioned between water and dichloromethane. The organic extracts were dried (MgSO4) and evaporated to give a solid which was purified by column chromatography on silica eluding with a mixture of ethyl acetate and hexane (20:80) to give 2-tert-butyloxycarbonylaminophenol (1.80 g); NMR Spectrum 9.7 (s, 1H), 7.7 (s, 1H), 7.6 (d, 1H), 6.7-6.9 (m, 3H), 1.45 (s, 9H); Mass Spectrum m/z=210 (M+H). | |
8.1 g | With triethylamine; In pyridine; at 0 - 25℃; for 12h; | 2-aminophenol (3.93 g, 36 mmol) was stirred with te/t-butoxycarbonyl dicarbonate (8.32 g, 38 mmol) in dry pyridine (30 mL) with triethylamine (4 mL) warming from 0C to 25C over 12 h. The volatiles were evaporated and the residue partitioned between diethyl ether and phosphate buffer (pH=10); the ether layer was washed with phosphate buffer then brine, dried on Na2S04, filtered and evaporated to yield 8.1 g of dark crude product which could be purified by column chromatography (20:1->5:1 Hex:EA), or by fractional crystallisations from acetone-hexane followed by hot hexane trituration. NMR spectra matched literature dataC45]: ^-NMR (400 MHz): delta = 8.15 (s br, 1H), 7.08-7.00 (m, 2H), 6.99 (d, 7.9 Hz, 1H), 6.88 (~t, 7.5 Hz, 1H), 6.69 (s, 1H), 1.56 (s, 9H) ppm. 13C-NMR (100 MHz): delta = 155.1, 147.6, 125.7, 125.5, 121.5, 120.7, 119.1, 82.2, 28.3 (x3) ppm. DIMS(+): 210 Th = [MH]+. |
180 g | In dichloromethane; Petroleum ether; at 25 - 40℃; for 10h; | A mixture of dichioromethane (500 ml) and 2-aminophenol (100 gms) were stirred for 15 minutes at 25-30C. Di-tert-butyl dicarbonate (240 gms) was slowly added to thereaction mixture at 25-30C. Heated the reaction mixture to 35-40C and stirred for 10 hours at the same temperature. Distilled off the solvent completely from the reaction mixture under reduced pressure. Petroleum ether (200 ml) was added to the obtained compound at below 40C and stirred for 15 minutes at the same temperature. Distilled off the solvent completely from the reaction mixture under reduced pressure. Petroleum ether (500 ml) was added to theobtained compound at 25-30C. Heated the reaction mixture to 50-55C and stirred for 1 hour at the same temperature. Cooled the reaction mixture to 25-30C and stirred for 3 hours at the same temperature. Filtered the solid, washed with petroleum ether and dried to get the title compound. Yield: 180 gms; Melting point: 140-144C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃;Inert atmosphere; | General procedure: To a solution of the corresponding N-Boc-aminophenol (1 mmol) in DMF (2 mL), K2CO3 (207 mg,1.5 mmol) and the required benzyl bromide (1 mmol) were added. The mixture was stirred at 60 Cuntil no starting material was observed by TLC. A saturated aqueous solution of ammonium chloridewas added (5 mL) and the resulting mixture extracted with EtOAc (10 mL ×3), the organic extractswashed with brine (20 mL) and dried over MgSO4. The crude product was purified by FC eluting withhexane/EtOAc (95:5 ? 9:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; | To the stirred solution of Phenol (1 mmol) in DMF (5 volume) was added imidazole (2 mmol) at room temperature and after 5 minutes TBDMS chloride (1.2mmol) was added and stirring continued untill completion of reaction (TLC monitoring).Next, charged water (5 volumes) to the reactio mass and extracted with diethyl ether (2X10 volumes). The combined organic layer was washed with brine(5 vol), dried (Na2SO4)and concentrated under vacuumwhich gave respective aryl TBDMS ethers in quantitative yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h; | To <strong>[186663-74-1]tert-butyl (2-hydroxyphenyl)carbamate</strong> (428 mg, 2.04 mmol) and E76C (748 mg, 1.95 mmol) in 3.9 mL of N,N-dimethylformamide was added potassium carbonate (807 mg, 5.84 mmol). The reaction was stirred at room temperature for 3 h. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate and concentrated. The residue was chromatographed on silica gel eluting with hexanes/ethyl acetate to provide E76D as a white solid (1.00 g, 100%); HPLC (Method 8) tR=4.21 min. |
Tags: 186663-74-1 synthesis path| 186663-74-1 SDS| 186663-74-1 COA| 186663-74-1 purity| 186663-74-1 application| 186663-74-1 NMR| 186663-74-1 COA| 186663-74-1 structure
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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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