Category: 366-99-4

366-99-4, name is 3-Fluoro-4-methoxyaniline, belongs to ethers-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. Product Details of 366-99-4

Cyanuric chloride (11.07 g, 60 mmol) was dissolved in 40 mL CH3CN and was cooled to about -20¡ã C. To this was added DIEA (11.5 mL, 60 mmol) followed by 3-fluoro-4-methoxyaninline (8.47 g, 60 mmol) in 20 mL CH3CN (reaction froze). The reaction was allowed to warm to room temperature after about 1 hour at -20¡ã C. TLC (2percent CH3OH/CH2Cl2) and mass spectroscopy indicated the presence of the compound 124. The reaction mixture was cooled to about 0¡ã C. before adding DIEA (11.5 mL, 66 mmol). 2-Aminomethyl-1-ethylpyrrolidine (7.77 g, 60 mmol) in CH3CN (10 mL) was added. The reaction was allowed to warm to rt and stirred overnight. Then DIEA (11.5 mL, 66 mmol) and S-(+)-2-methoxyethylpyrrolidine (6.91 g, 60 mmol) in 20 mL 1,4-dioxane were added. The reaction was heated at about 50¡ã C. overnight. The solvent was removed in vacuo, and the resulting residue was purified by flash chromatography on silica gel packed in ethyl acetate. The front running impurities were removed and subsequently the eluent was increased in polarity to 10percent CH3OH:ethyl acetate. The material collected from the column was then dissolved in water and extracted in CH2Cl2 (4 times), dried over MgSO4, and concentrated to dryness to give a brown solid 145 (9.7 g, 27.6percent yield), 71-72¡ã C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 5.37 min, 90.3percent purity; 1H NMR (600 MHz, CDC3, 55¡ã C.) delta 7.69 (s, 1H), 7.08 (d, J=7.8 Hz, 1H), 6.86 (t, J=9 Hz, 1H), 4.29 (s, 1H), 3.90-3.96 (m, 1H), 3.84 (s, 3H), 3.63-3.81 (m, 6H), 3.35 (s, 3H), 3.23-3.25 (m, 1H), 2.85 (broad s, 1H), 2.78 (broad s 1H), 2.14 (broad s, 2H), 1.89-2.04 (m, 6H), 1.37 (apparent t, J=7.2 Hz, 3H); 13C NMR (150.8 MHz, CDCl3, 55¡ã C.) delta 165.8, 163.8 (2C), 152.3 (d, Jc-f=243.5 Hz), 143.0 (142.9, rotamer or diastereumer), 133.7 (133.67, rotamer or diastereomer), 115.0, 114.4, 109.1 (108.9, rotamer or diastereomer), 72.8, 66.6, 59.0, 57.0, 56.6, 53.7, 51.0, 46.8, 42.2, 28.4 (28.2, rotamer or diastereomer), 23.1 (23.0, rotamer or diastereomer), 10.9; MS (ESI) mn/z 460.2 (M+H, 44.7), 251.1 (47.7), 235.1 (27.5), 231.1 (37.4), 230.6 (100), 214.6 (36.5).

The synthetic route of 366-99-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krishma Reddy, Velagala Venkata Rama Murali; Sesila Sridevi, Bhatlapenumarthy; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209882; (2004); A1;,
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366-99-4, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 366-99-4, name is 3-Fluoro-4-methoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Preparation 66A: 4-Bromo-3-fluoro-N-(3-fluoro-4- methoxyphenyl)benzenecarboximidamide To a solution of EtMgBr (48 mL, 42.55 mmol, 0.9 M) in THF (24 mL) was added a solution of 3-fluoro-4-methoxyaniline (3 g, 21.28 mmol) in THF (30 mL) at r.t. The mixture was stirred for 30 min at r.t. A solution of 4-bromo-3-fluorobenzonitrile (4.657 g, 23.40 mmol) in THF (20 mL) was added dropwise at r.t. and stirred overnight at r.t. LC/MS showed the reaction was completed, H20 was added and extracted with EA, dried, concentrated and purified by flash chromatography on silica gel (PE/EA=3/1 to EA) to afford 4-bromo-3-fluoro-N-(3-fluoro-4-methoxyphenyl)benzenecarboximidamide (4.68 g, 65percent). [M+H] Calc’d for Ci4HnBrF2N20, 341; Found, 341.

The synthetic route of 3-Fluoro-4-methoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; QUANTICEL PHARMACEUTICALS, INC.; CHEN, Young, K.; KANOUNI, Toufike; NIE, Zhe; STAFFORD, Jeffrey, Alan; VEAL, James, Marvin; (166 pag.)WO2016/4105; (2016); A1;,
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366-99-4, A common compound: 366-99-4, name is 3-Fluoro-4-methoxyaniline, belongs to ethers-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Example 4; Parallel Synthetic Method B, for Library II Compounds; Fifty mL (13.5 mmol) of the prepared (4,6-dichloro-[1,3,5]triazin-2-yl)-(3-fluoro-4-methoxy-phenyl) amine solution was divided equally (2 mL or 0.54 mmol each) among 25 barcoded, 40 mL scintillation vials. Individual solutions of each R2NHR (where R2 amine indicates Monomer 2 in Table 2, 0.542 mmol) and DIEA (77 mg /104 muL, 0.596 mmol) in 0.5 mL of CH3CN were prepared and added to the correspondingly labeled 40 mL vials. The resulting solutions were shaken on the J-KEM block overnight at room temperature and then placed in a freezer (about -14 ¡ã C.) without purification until the next reaction.; Example 5; Parallel Synthetic Method C, for Library III Compounds; In an oven-dried round bottom flask, a solution of cyanuric chloride (5.0 g, 27.1 mmol) in 1,4-dioxane (40 mL) was cooled to freezing in a CH3CN/dry ice bath. To this frozen solution was added 40 mL of CH3CN, followed by DIEA (3.85 g/5.19 mL, 29.8 mmol). A solution of 3-fluoro-p-anisidine (3.83 g, 27.1 mmol) in 10 mL of CH3CN was then added slowly via syringe. The reaction mixture was stirred at about -20¡ã C. for about 1h and allowed to warm to room temperature over 1 h. The resulting 2-amino-4,6-dichlorotriazine solution was carried to the next step without purification.

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 3-Fluoro-4-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krishna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209881; (2004); A1;,
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366-99-4, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 366-99-4, name is 3-Fluoro-4-methoxyaniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 55 Synthesis of N2-cycloheptyl-N4-(2-dimethylamino-ethyl)-N6-(3-fluoro-4-methoxy-phenyl)-1,3,5-triazine-2,4,6-triamine (150) Cyanuric chloride (1.84 g, 10 mmol) in CH3CN (20 mL) was cooled to about -10¡ã C. was added 3-fluoro-p-anisidine (1.41 g, 10 mmol) followed by DIEA (1.8 mL, 10 mmol). The reaction was stirred for about 45 min then at room temperature for about 45 min under an N2 atmosphere. Cycloheptylamine (1.26 mL, 10 mmol) was added followed by DIEA (1.8 mL, 10 mmol) and the reaction was stirred at room temperature overnight. N,N-dimethylethylenediamine (1.1 mL, 10 mmol) was added followed by DIEA (1.8 mL, 10 mmol) and the mixture was heated at reflux under N2 overnight. The reaction was diluted with ethyl acetate, washed with brine, and dried over anhydrous K2CO3. The material (1.178 g) was purified by silica gel column chromatography to afford a solid 150 (1.178 g, 28percent), mp 73-76¡ã C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 10.8 min, 95.1percent purity; MS (ESI): m/z 418 (M+H, 100), 373 (11.9), 322 (7.8), 277 (6.8), 162 (3.6).

The synthetic route of 3-Fluoro-4-methoxyaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krlshna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209880; (2004); A1;,
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Adding a certain compound to certain chemical reactions, such as: 366-99-4, name is 3-Fluoro-4-methoxyaniline, belongs to ethers-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 366-99-4, 366-99-4

Cyclobutanone (14.0 g, 200 mmol), Acetic acid (1.8 g, 30 mmol), and Sodium triacetoxyborohydride (6.36 g, 30 mmol) were added to a solution of 3-Fluoro-4-methoxyaniline (2.82 g, 20 mmol) in DCM (120 mL) and the mixture was stirred at RT for 12 hr. Water was added to quench the reaction and the mixture was extracted with DCM. The solvent was removed under and the residue was purified by silica gel chromatography to afford N-Cyclobutyl-3-fluoro-4-methoxyaniline (2.4 g, 61percent yield). 1H NMR (300 MHz, CDC13) delta ppm 6.81 (t, J= 9.1 Hz, 1H), 6.40-6.19 (m, 2H), 3.82 (s, 3H), 3.79-3.77 (m, 1H), 3.65 (s, 1H), 2.50-2.30 (m, 2H), 1.80-1.78 (m, 4H).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 3-Fluoro-4-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JIANGSU ASCENTAGE BIOMED DEVELOPMENT INC.; CHEN, Jianyong; ZHOU, Yunlong; WANG, Shaomeng; GUO, Ming; YANG, Dajun; JIAO, Lingling; JING, Yu; QIAN, Xu; LIU, Liu; BAI, Longchuan; YANG, Chao-Yie; MCEACHERN, Donna; WO2015/127629; (2015); A1;,
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Some common heterocyclic compound, 366-99-4, name is 3-Fluoro-4-methoxyaniline, molecular formula is C7H8FNO, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 366-99-4

To 124 (1.09 g, 3.5 mmol) dissolved in acetone (25 mL) was added 3-fluoro- p-anisidine (0.54 g, 3.5 mmol) in acetone (5 mL) followed by addition of 2.5 N NaOH (1.4 mL, 3.5 mmol) and water (3.5mL). The reaction mixture was stirred and heated at reflux for 3 hours. The reaction mixture was extracted three times using dichloromethane ; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was filtered, concentrated in vacuo, and the resulting solid was dried overnight under vacuum to yield white solid (E15) (1.332 g,97percent) ; mp194 C ; HPLC: Inertsil ODS 3V C18,40 : 30: 30 v: v: v[KH2P04(0. 01 M, pH 3.2) : CH30H: CH3CN], 264nm,Rt 33.2 min, 97.6percent purity; MS (TOF ES+)mlz 396 (35.0) ; 394 (M+H, 100).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 366-99-4, its application will become more common.

Reference:
Patent; REDDY US THERAPEUTICS, INC.; WO2004/26844; (2004); A1;,
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In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 366-99-4 as follows. 366-99-4

To a mixture of cyanuric chloride (0.368 g, 2 mmol) in CH3CN at approximately -10 to -20 C. was added 3-fluoro-p-anisidine (0.28 g, 2 mmol) in CH3CN followed by the addition of N,N-diisopropylethylamine (DIEA) (0.35 mL, 2 mmol) and stirred for an hour. The reaction mixture was then allowed to reach room temperature for an hour. The second step was continued without further purification. Cycloheptylamine (0.25 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at rt. The third step was also preceded without any further purification. S-(-)-2-aminomethyl-N-ethyl pyrrolidine (0.29 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over potassium carbonate, filtered, and concentrated under reduced pressure affording 0.920 g crude material. The crude material was purified by column chromatography to yield a white solid 139 (0.550 g, 60%), mp 75-77 C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 7.9 min, 95.9% purity; MS (ESI): m/z 458 (M+H, 100).

According to the analysis of related databases, 366-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krlshna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209880; (2004); A1;,
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The chemical industry reduces the impact on the environment during synthesis 366-99-4, name is 3-Fluoro-4-methoxyaniline, I believe this compound will play a more active role in future production and life. 366-99-4

Cyanuric chloride (1.84 g, 10 mmol) inCH3CN (20 mL) was cooled toabout-10 C was added3-fluoro-p-anisidine (1. 41 g, 10 mmol) followed by DIEA(1. 8 mL, 10 mmol). The reaction was stirred for about 45 min then at room temperature for about 45 min under an N2 atmosphere. Cycloheptylamine (1.26 mL, 10 mmol) was added followed by DIEA (1.8 mL, 10 mmol) and the reaction was stirred at room temperature overnight.N,N-dimethylethylenediamine (1. 1 mL, 10 mmol) was added followed by DIEA (1.8 mL, 10 mmol) and the mixture was heated at reflux under N2 overnight. The reaction was diluted with ethyl acetate, washed with brine, and dried over anhydrousK2C03. The material (1.178 g) was purified by silica gel column chromatography to afford a solid 150 (1.178 g,28percent), mp73-76 C ; HPLC: Inertsil ODS-3VC18, 40: 30: 30[KH2PO4 (O. 01M, pH 3.2) :CH30H :CH3CN], 264 nm,Rt 10.8 min, 95. 1percent purity ; MS (ESI):iiilz418 (M+H, 100), 373(11. 9), 322 (7.8), 277 (6.8), 162 (3.6).

The chemical industry reduces the impact on the environment during synthesis 366-99-4. I believe this compound will play a more active role in future production and life.

Reference:
Patent; REDDY US THERAPEUTICS, INC.; WO2004/26844; (2004); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

366-99-4, name is 3-Fluoro-4-methoxyaniline, belongs to ethers-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. 366-99-4

To a stirred suspension of 3-fluoro-p-anisidine (3.00 g, 21 mmol) in CH2Cl2 (10 mL) is added acetic anhydride (2.0 mL, 21 mmol) over 1 h while maintaining the temperature between 25-30¡ã C. using a cold water bath. The solution is then stirred for 2 h at 25¡ã C. Additional 1 mL of acetic anhydride is added to the solution, which is then stirred for an additional 2 h. Hexane (30 mL) is slowly added to the mixture over 1 h. The product is collected by filtration, concentrated in vacuo and dried in oven to give 3.40 g (90percent yield) of N-(3-fluoro-4-methoxyphenyl)acetamide as tan crystals. 1H NMR (400 MHz, CDCl3) delta 7.41, 7.19, 7.11, 6.90, 3.87, 2.16. In a 100 mL, three-necked flask equipped with a thermometer and a dropping funnel chilled in an ice-salt bath, N-(3-fluoro-4-methoxyphenyl)acetamide (3.0 g, 16 mmol) is dissolved in 98percent sulfuric acid, care being taken that the temperature does not rise above 5¡ã C. To this solution 2.6 mL of nitric acid is added dropwise at such a rate that the temperature does not rise above 5¡ã C. After all the nitric acid is added, the viscous orange mass is poured onto 50 g of cracked ice and the mixture is thoroughly stirred. The yellow crystals that separate are filtered off and thoroughly washed with water to yield 3.33 g (89percent yield) of N-(5-fluoro-4-methoxy-2-nitrophenyl)acetamide as yellow crystals. 1H NMR (400 MHz, DMSO-d6) delta 10.60, 10.17, 7.75, 7.73, 7.62, 7.59, 4.03, 3.92, 2.06. A suspension of N-(5-fluoro-4-methoxy-2-nitrophenyl)acetamide (3.0 g, 13 mmol) in 38 mL of water, 38 mL of HCl and 15 mL of ethanol is refluxed for 30 minutes. On cooling, crystals that separate are recrystallized from ethanol to yield 0.71 g (29percent yield) of 5-fluoro-4-methoxy-2-nitroaniline as red crystals. 1H NMR (400 MHz, CDCl3) delta 7.68, 6.56, 6.04, 3.87. Example 603 is obtained according to Method F, making non-critical modifications. Yield 60percent. HRMS (ESI) calcd for C12H11FN4O5+H 311.0792 found 311.0798.

Statistics shows that 366-99-4 is playing an increasingly important role. we look forward to future research findings about 3-Fluoro-4-methoxyaniline.

Reference:
Patent; Piotrowski, David W.; Rogers, Bruce N.; McWhorter JR., William W.; Walker, Daniel Patrick; Corbett, Jeffrey W.; Groppi JR., Vincent E.; Rudmann, Daniel G.; US2003/236287; (2003); A1;,
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366-99-4, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 366-99-4, name is 3-Fluoro-4-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows.

28.a. 1-(2-amino-4-fluoro-5-methoxyphenyl)-1-propanone (This product is obtained according to Sugasawa T; Toyoda T; Adachi M; Sasakura K, J Am. Chem. Soc., 100 (1978), p.4842-4852). Boron trichloride (1M in heptane, 156 ml, 156 mmol) is added dropwise, under an argon atmosphere at 0¡ã C. to a solution of 3-fluoro-4-methoxy-aniline (20 g, 142 mmol) in anhydrous dichloromethane (200 ml). The pink suspension thus obtained is maintained under agitation for 5 minutes, then propionitrile (33 ml, 420 mmol) is added dropwise followed by aluminium trichloride (20.8 g, 156 mmol) in small portions. The reaction medium is heated under reflux for 3 hours, cooled down to 0¡ã C., hydrolyzed by cautiously adding 2N hydrochloric acid (100 ml), then heated at reflux for 45 minutes. After cooling down to 0¡ã C. a precipitate is obtained which is filtered out, washed with dichloromethane, then taken up in water (300 ml). The aqueous phase is basified to an alkaline pH, extracted with dichloromethane then ethyl acetate. The organic phase is dried (MgSO4) then evaporated to produce a crude product which is purified by column chromatography (SiO2, AcOEt/Hpt: 1/99 to 20/80). 15.3 g of a yellow solid is obtained. NMR-1H (CDCl3): 1.20 (t, 3H); 2.92 (q, 2H); 3.83 (s, 3H); 6.2 (s, 2H); 6.40 (d, 2H); 7.32 (d, 2H). IR(KBr): 857; 1148; 1240; 1561; 1583; 1662.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Bigg, Dennis; Lavergne, Olivier; Pla Rodas, Francesc; Pommier, Jacques; Ulibarri, Gerard; Harnett, Jerry; Rolland, Alain; Liberatore, Anne-Marie; Lanco, Christophe; Cazaux, Jean-Bernard; Le Breton, Christine; Manginot, Eric; US2003/4150; (2003); A1;,
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