Structure of 13519-75-0
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| CAS No. : | 13519-75-0 |
| Formula : | C8H10ClN |
| M.W : | 155.63 |
| SMILES Code : | CCNC1=CC=C(Cl)C=C1 |
| English Name : | 4-Chloro-N-ethylaniline |
| MDL No. : | MFCD00018594 |
| InChI Key : | KLWDPIXDUVYHMS-UHFFFAOYSA-N |
| Pubchem ID : | 587841 |
* 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.

[ 13519-75-0 ]
[ 536-38-9 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With C20H25Cl2CoN3; sodium triethylborohydride; In 1,2-dimethoxyethane; at 100℃; for 6h;Inert atmosphere; | Under an inert atmosphere, the substrate 4-chloroacetanilide (170 mg, 1 mmol), polymethylhydrosiloxane (668 μL, 3 mmol), Co-2 catalyst (9.0 mg, 0.02 mmol), sodium triethylborohydride (40 μL, 0.04 mmol)were sequentially added to the reaction tube and ethylene glycol dimethyl ether (2 mL), and the resulting mixture was stirred well.The reaction was carried out in an oil bath at 100C for 6 hours. The reaction system was cooled to room temperature, diluted and quenched by adding ethyl acetate, and concentrated. The crude product was subjected to flash silica gel column chromatography to obtain 109 mg of light yellow oily liquid, yield: 70%. |
[ 104-15-4 ]
[ 13519-75-0 ]


[ 13519-75-0 ]

[ 13519-75-0 ]
[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In hexane; toluene; at 10 - 20℃; | To a solution of iV-ethyl-4-chloroaniline (650 mg, 4.18 mmol) in anhydrous toluene at 10 0C was slowly added a 2M solution of trimethylaluminium in hexanes (2.1 mL, 4.18 mmol). The reaction mixture was stirred at room temperature until gas evolution stopped. A second round bottom flask was charged with cw-2-methyl-l-(pyridine-4-carbonyl)-l,2,3,4-tetrahydro-quinoline-4- carboxylic acid methyl ester (370 mg, 1.19 mmol) and the preformed aluminum amide was added. The resulting reaction mixture was refluxed for 20 hours. The reaction was concentrated, quenched with IM aqueous hydrochloric acid at 0 0C (exothermic.), basified with IM aqueous sodium hydroxide, and extracted with ethyl acetate. The resulting organic layer was separated, washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford an orange oil which was purified via flash chromatography (1% methanol / methylene chloride) followed by HPLC to provide (+/-)-frøtts-2-methyl-l-(pyridine-4-carbony I)- 1,2,3, 4-tetrahydro-quinoline-4- EPO <DP n="96"/>carboxylic acid (4-chloro-phenyl)-ethyl-amide (11%). 1H-NMR (CDCl3) δ: 1.02 - 1.18 (m, 6H), 1.60- 1.70 (m, IH), 2.45 - 2.55 (m, IH), 3.60 - 3.70 (m, IH), 3.80 (q, 2H), 4.98 - 5.10 (m, IH), 6.40 (d,IH), 6.90 (m, 2H), 7.00 (t, IH), 7.30 (m, 2H), 7.50 (d, 2H), 7.60 (d, 2H), 8.55 (d, 2H). MS m/z:434/436 (M+l). |

[ 13519-75-0 ]

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 39% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 18 - 20h; | A round bottom flask with magnetic stirrer was charged with 2-methyl-l-(4- trifluoromethyl-benzoyl)-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (886 mg, 2.44 mmol) in anhydrous pyridine (25.0 mL). To the reaction was added <strong>[13519-75-0]N-ethyl-p-chloroaniline</strong> (0.410 mL, 2.95 mmol), followed by EDCI (833 mg, 4.34 mmol). The reaction was stirred at room temperature under an argon atmosphere for 18-20 hours. The reaction was poured into a 1:1 mixture of water/brine (50 mL) and extracted with ethyl acetate (3 x 35 mL). The combined extractions were washed with brine (1 x 50 mL), dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford a brown residue. The residue was purified via silica gel chromatography (hexanes / ethyl acetate) to yield (+/-)-trans-2-methyl-l-(4-trifluoromethyl-benzoy I)- 1,2,3, 4-tetrahydro-quinoline-4- carboxylic acid (4-chloro-phenyl)-ethyl-amide (39%). 1H-NMR (CDCl3) δ: 1.02 (d, 3H), 1.12 (t, 3H), 1.64 - 1.74 (m, IH), 2.49 - 2.58 (m, IH), 3.59 - 3.72 (m, IH), 3.77 - 3.90 (m, 2H), 5.03 - 5.14 (m, IH), 6.35 - 6.41 (m, IH), 6.74 - 6.84 (m, 2H), 6.89 - 6.95 (m, IH), 7.17 - 7.25 (m, 2H), 7.44 - 7.52 (m, 2H), 7.63 - 7.69 (m, 2H). MS m/z: 501 (M+l). |

[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 14% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 18 - 20h; | A round bottom flask with magnetic stirrer was charged with l-(6-methoxy-pyridine-3- carbonyl)-2-methyl-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (190 mg, 0.58 mmol) in anhydrous pyridine (1.5 mL). To the reaction was added <strong>[13519-75-0]N-ethyl-p-chloroaniline</strong> (185 mg, 1.19 mmol), followed by EDCI (156 mg, 0.82 mmol). The reaction was stirred at room temperature under an argon atmosphere for 18 - 20 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford a yellow oil (350 mg). The crude material was purified via silica gel EPO <DP n="85"/>chromatography (1 % methanol / methylene chloride) followed by HPLC to yield (+/-)-trans-l-(6- methoxy-pyridine-3-carbonyl)-2-methyl-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro- phenyl)-ethyl-amide (14%). 1H-NMR (CDCl3) δ: 1.05 (d, 3H), 1.13 (t, 3H), 1.65 - 1.75 (m, IH), 2.50 - 2.60 (m, IH), 3.60 - 3.70 (m, IH), 3.80 (q, 2H), 3.95 (s, 3H), 5.02 - 5.10 (m, IH), 6.50 (d, IH), 6.60 (d, IH), 6.75 (d, IH), 6.85 - 7.00 (m, 2H), 7.20 (m, 2H), 7.50 (d, 2H), 7.75 (d,lH), 8.40 (s, IH). MS m/z: 464/466 (M+l). |

[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | l-(4-Methoxy-benzoyl)-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (approx. 1.47 mmol) was suspended in methylene chloride (10 mL) to which one drop of dimethylformamide was added. Oxalyl chloride (375 mg, 275 uL, 2.95 mmol) was added. Vigorous bubbling ensued, followed by dissolution of the starting material. After stirring for 4 hours at room temperature, the yellow solution was concentrated and azeotroped with toluene to remove excess oxalyl chloride. The resulting acid chloride solution was dissolved in methylene chloride (10 mL). Diisopropylethylamine (569 mg, 768 uL, 4.41 mmol) was added, followed by <strong>[13519-75-0]4-chloro-N-ethylaniline</strong> (457 mg, 2.93 mmol). The mixture was stirred at room temperature overnight. The reaction was poured into ethyl acetate and washed with water and brine. The combined organics were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (ethyl acetate / hexanes gradient) to afford (+/-)-l-(4-methoxy-benzoyl)-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (193 mg) as a foam. 1H-NMR (CDCl3) δ: 1.17 (t, 3H), 2.06 - 2.26 (m, 2H), 3.57 - 3.70 (m, 2H), 3.73 - 3.87 (m, 5H), 4.02 (dd, IH), 6.52 (d, IH), 6.66 - 6.74 (m, 2H), 6.84 (ddd, IH), 6.93 - 7.06 (m, 2H), 7.17 - 7.24 (m, 2H), 7.37 - 7.43 (m, 2H). MS m/z: 449 (M+l). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 72h; | Example 15 (4-Chloro-phenyl)-ethyl-((2S,4S)-4-fluoro-pyrrolidin-2-ylmethyl)-amine To a solution of N-ethyl-4-chloro-aniline (0.31 g, 2.0 mmol) in dichloromethane (8 ml) were added (2S,4S)-tert-butyloxycarbonyl-4-fluoro-pyrrolidine-2-carboxylic acid (0.47 g, 2.0 mmol), bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (0.76 g, 3.0 mmol) and diisopropylethylamine (0.39 g, 3.0 mmol). The mixture was stirred for 3 days at room temperature. Aqueous sodium bicarbonate solution (20 ml) was added and the mixture was extracted with dichloromethane (3*20 ml). The combined organic layers were dried with magnesium sulphate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (SiO2: heptane/ethyl acetate=2:1) to yield a light yellow oil (0.55 g), that was dissolved in tetrahydrofurane (15 ml). Borane-tetrahydrofurane-complex (7.4 ml, 1M, 7.4 mmol) was added and the mixture was heated at 60 C. overnight. After cooling 5 drops of aqueous hydrochloric acid (4N) were added and the solvent was evaporated. The white residue was dissolved in aqueous hydrochloric acid (4N, 10 ml) and heated at 60 C. for 1 hour. After cooling aqueous sodium hydroxide solution was added until basic pH and the mixture was extracted with dichloromethane (2*30 ml). The combined organic layers were dried with magnesium sulphate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (column: Isolute Flash-NH2 from Separtis; eluent: ethyl acetate/heptane 1:1) to yield a light yellow oil, (0.137 g, 27%); MS (ISP): 257.1 ((M+H)+.). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 59% | With pyridine; dmap; In dichloromethane; at 0℃; | General procedure: To a stirred solution of amine 1 (5 mmol, 1 equiv), pyridine (2-3equiv) and DMAP (0.1-0.5 equiv) in DCM (30 mL) at 0 C was slowlyadded 2-chloroethanesulfonyl chloride (2) (6 mmol, 1.13 equiv). Theresulting mixture was stirred at 0 C until the amine had been consumed(as determined by TLC). The reaction was then quenched withwater (10 mL) and extracted with DCM (3 × 30 mL). The combined organicextracts were washed with brine (10 mL) and dried over anhydrous Na2SO4. The solvent was removed under vacuum and the residuewas purified by column chromatography (eluting with 5-10%EtOAc in petroleum ether) to afford the product 3. |

[ 13519-75-0 ]

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With copper(I) triflate benzene complex; (R)-BICMAP; N-ethyl-N,N-diisopropylamine; In methanol; at -10℃; for 18h;Inert atmosphere; | General procedure: Under an argon atmosphere, CuOTf·0.5C6H6 (2.5mg, 10μmol) was added to (R)-BICMAP (12.7mg, 20μmol) in MeOH (1mL). The mixture was stirred for 1h at 60C and concentrated under reduced pressure. Propargylic acetate 1 (0.20mmol) in MeOH (1mL), amine 2 (0.30mmol), and diisopropylethylamine (42.0μL, 0.24mmol) were added to the copper complex. A mixture was stirred at -10C under an argon atmosphere. After 18h, the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane or hexane/EtOAc=250-100/1). 4.2.10 (S)-(-)-N-Ethyl-N-(1-phenyl-2-propynyl)-p-chloroaniline 3j (Table 2, entry 11) 67% Yield (36.2mg), 88% ee; [α]20D=-27.1 (c 0.22, CHCl3); yellow oil; 1H NMR (CDCl3, 300MHz) δ 1.07 (t, J=7.0Hz, 3H), 2.53 (d, J=2.4Hz, 1H), 3.22-3.34 (m, 2H), 5.61 (s, 1H), 6.84 (d, J=8.9Hz, 2H), 7.18 (d, J=8.7Hz, 2H), 7.30-7.39 (m, 3H), 7.55 (d, J=7.3Hz, 2H); 13C NMR (CDCl3, 75MHz) δ 13.2, 42.8, 56.2, 74.7, 80.8, 117.2, 123.5, 127.4, 127.8, 128.5, 128.8, 137.7, 146.5; EI-MS m/z (rel intensity) 269 (M+, 14); HRMS (ESI-orbitrap) m/z calcd for C17H16NCl+H 270.1038, found: 270.1044; HPLC (Daicel CHIRALPAK AD-H, 0.46 ×25cm, UV 254nm, hexane/2-propanol=97:3, 1.0mL/min) tR=5.5min (minor) and 6.0min (major). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With N-ethyl-N,N-diisopropylamine; In toluene; at 90℃; for 18h; | General procedure: A mixture of asubstituted aniline (33aem) (5.5 mmol), N-ethyldiisopropylamineand alkyl halide (34aec) or ethyl sulfate (34d) in the molar ratio of1:1:1 in toluene (21 ml) was stirred and heated at 90∘C for 18 h. Inthe cases listed below it was necessary to vary the conditions of reaction as summarized in Table 1.The resulting suspension was taken up with ethyl acetate. The organic phase was washed with water then dried over anhydrous sodium sulfate. On evaporation of the solvent, in most cases a solidor an oily residuewas obtained. Purification was performed by flash chromatography on a silica gel column eluting with the following mixture of solvents: ethyl acetate/petrol ether 40-60∘, in the ratio of 6:4 (35, 42); 7:3 (52); 8:2 (41, 43, 48, 51, 53, 62, 65); 9:1 (38, 39,45, 46, 47, 50); 95:5 (36, 37, 44, 55, 56, 57, 58, 59, 60, 61); 98:2 (64);petrol ether 40-60∘/diethyl ether 9:1 (49); toluene/ethyl acetate 95:5 (63); chloroform/methanol 95:5 (54), chloroform/methanol 98:2 (66). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 61% | In N,N-dimethyl acetamide; at 20℃; for 96h; | General procedure: A mixture of N-alkylaniline (35e66) (2.46 mmol) and bromomethylquinoxaline(32) (1.28 mmol) in dry dimethylacetamide(DMAa) (23 ml) was stirred at room temperature for 72 h. In thecase of compounds 12, 14, 15 the reactionwas prolonged up to 96 h,while in the case of 30 was necessary to heat at 60∘C. (In the case ofpreparation of compound 2 an equimolar amount of the reactants was used in acetonitrile in the presence of 1.5 mmol Cs2CO3 and the suspensionwas stirred under heating at 40∘C for 96 h). Then water was added to the mixture to give crude products of 1-31 as gums or crystalline precipitates which were collected, thoroughly washed. Purification was accomplished by silica gel column chromatography on eluting with petrol ether 40-60∘C/ethyl acetate in the following ratio 9:1 (2, 3, 13, 19, 23, 29); 95:5 (9, 12, 15, 21, 22, 24, 25,26, 27, 30); 8:2 (7, 8, 28, 31); 6:4 (1, 20). In the case of the derivatives5, 6, 10, 11, 14, 16, 17, 18, further purification was carried out by trituration with petrol ether followed by filtration. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With [(phenylbenzothiazole)2Ir(nBu)3]OTf; In 5,5-dimethyl-1,3-cyclohexadiene; at 155℃; for 10h;Inert atmosphere; Schlenk technique; | A novel process for the reaction of a secondary amine by reaction of 4-chloroaniline with triethylamine, comprising the following process steps:Under nitrogen protection,To a 50 mL Schlenk tube was added 4-chloroaniline (128 mg, 1 mmol)Triethylamine (304 mg, 3 mmol),[(Bt) 2 * Ir * P (nBu) 3] OTf (9.6 mg, 0.01 mmol, 1.0 mol%),Add 2.0mL xylene;The reaction solution was reacted at 155 C for 10 h,The resulting solution was separated on a silica gel column from 200 to 300 mesh (eluent 1:10 ethyl acetate / petroleum ether)After removal of the solvent,To get the product.Yield: 91%. |
| 58% | With iridium(III) chloride; (S)-methyl 2-(2-(1H-benzo[d][1,2,3]triazol-1-yl)acetamido)propanoate; sodium hydroxide; In para-xylene; at 150℃; for 20h;Schlenk technique; | General procedure: A solution of IrCl3 (2 mol%, 0.02 mmol), L1 (2.4mol%, 0.024mmol), sodium hydrate (0.20mmol) and xylene (3mL) were stirred in a Schlenk tube under RT for 1 h. Subsequently, p-toluidine(1.00 mmol), triethyl amine (1.0mL), and sodium hydrate (1.00mmol) were added. The mixture was heated under150oC for 20 h, and then cooled to room temperature. The resulting solution was directly purified by column chromatography with petroleum ether/ethyl acetate (10:1) as eluent to give the desired product 3a. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 110℃; for 6.5h; | General procedure: A solution of the corresponding ω-halonitrile (2.5 mmol) in dimethylformamide (0.5 ml)was added over 1.5 h to a mixture of the arylamine (5 mmol), K2CO3 (345.5 mg, 2.5 mmol)and KI (830 mg, 5 mmol) in dimethylformamide (3 ml) for compounds 1 or dimethylformamide(0.6 ml) and dimethoxyethane (2.4 ml) for compounds 4. The mixture wasstirred at the indicated temperature for 5 h. After completion of the reaction, as indicatedby TLC, the mixture was diluted with ethyl ether (50 ml) and water (10 ml). The aqueousphase was separated and additionally extracted once with ethyl ether (30 ml). The combinedorganic layers were washed with water, dried over anhydrous sodium sulfate andfiltered. The filtrate was evaporated in vacuo and the resulting crude material was dissolvedin tetrahydrofuran and treated with 1M borane/THF (30 ml). The solution was refluxedfor 2 h, cooled and treated with methanol. The solvent was then evaporated in vacuo.The residue was refluxed with 10% hydrochloric acid (30 ml) for 2 h, filtered and madealkaline with 10% aqueous sodium hydroxide. The alkaline mixture was extracted withethyl acetate (4 × 20 ml). The organic phase was washed with water (5 ml), dried oversodium sulfate and filtered. The solvent was evaporated in vacuo and the crude product waspurified by column chromatography (silica gel, dichloromethane:methanol:isopropylamine10:1:0.1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 110℃; for 6.5h; | General procedure: A solution of the corresponding ω-halonitrile (2.5 mmol) in dimethylformamide (0.5 ml)was added over 1.5 h to a mixture of the arylamine (5 mmol), K2CO3 (345.5 mg, 2.5 mmol)and KI (830 mg, 5 mmol) in dimethylformamide (3 ml) for compounds 1 or dimethylformamide(0.6 ml) and dimethoxyethane (2.4 ml) for compounds 4. The mixture wasstirred at the indicated temperature for 5 h. After completion of the reaction, as indicatedby TLC, the mixture was diluted with ethyl ether (50 ml) and water (10 ml). The aqueousphase was separated and additionally extracted once with ethyl ether (30 ml). The combinedorganic layers were washed with water, dried over anhydrous sodium sulfate andfiltered. The filtrate was evaporated in vacuo and the resulting crude material was dissolvedin tetrahydrofuran and treated with 1M borane/THF (30 ml). The solution was refluxedfor 2 h, cooled and treated with methanol. The solvent was then evaporated in vacuo.The residue was refluxed with 10% hydrochloric acid (30 ml) for 2 h, filtered and madealkaline with 10% aqueous sodium hydroxide. The alkaline mixture was extracted withethyl acetate (4 × 20 ml). The organic phase was washed with water (5 ml), dried oversodium sulfate and filtered. The solvent was evaporated in vacuo and the crude product waspurified by column chromatography (silica gel, dichloromethane:methanol:isopropylamine10:1:0.1). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogen; at 170℃; under 15001.5 Torr; for 4h; | General procedure: The nitroarenes (0.81 mmol), alcohols (3 ml) and catalysts(50 mg) were placed in reactor. Before hydrogenationalkylationtandem experiments, the reactor was purged with N2 and H2 toremove the air and N2 for three time, respectively. The reactionmixture was isolated by the magnet, and the conversion and yieldsof reactions of hydrogenationalkylation tandem reaction catalyzed by the catalysts were analyzed by using NMR and GC-MS. |

[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 65% | With pyridine; at 0 - 20℃; for 12h;Inert atmosphere; | Pyridine (0.38 mL, 4.8 mmol, 3 eq) was added to a solution of 4- chloro-N-ethylaniline (0.25 g, 1.6 mmol, 1 eq) and 37.1 (0.983 g, 3.2 mmol, 2 eq) in anhydrous DCM (2.5 mL) at 0 C. The reaction mixture was stirred at room temperature for 3h. Water (20 mL) was added, and the mixture was extracted using DCM (2 x 10 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and compound was eluted using 10% EtOAc in hexanes to afford pure I-513 (0.44 g, 65%). (ES, m/z): [M+H]+ 424.1, LCMS purity: 100%, 1H -NMR (400 MHz, DMSO-d6, ppm) d 1.01 (t, J = 7.1 Hz, 3H), 3.82 (q, J = 7.1 Hz, 2H), 7.16-7.24 (m, 2H), 7.41-7.51 (m, 2H), 7.65 (s, 1H), 7.97 (d, J = 2.5 Hz, 1H), 11.20 (br s, 1H). |
[ 13519-75-0 ]

[ 13519-75-0 ]
[ 13519-75-0 ]

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