Category: 22236-08-4

22236-08-4, name is 3-(Difluoromethoxy)aniline, 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. SDS of cas: 22236-08-4

General procedure: The synthesis was carried out by using the synthetic method a. To a solution of 2-picolinic acid (0.871 g,7.08 mmol), N-hydroxybenzotriazolehydrate (HOBt.H2O,1.084 g, 7.08 mmol), diisopropylethylamine(DIPEA, 1.83 g, 14.17mmol) and N-(3-methylaminopropyl)-N?-ethylcarbodiimidehydrochloride (EDCHCl, 2.036 g, 10.63mmol) in anhydrous 1,4-dioxane (60 mL) was added 3-fluoro-3-methoxyanilline (1.00 g, 7.08 mmol) at room temperature. The mixture was heated to 50 oC and stirred overnight. To the reaction mixture was added 300 mL of dichloromethane, and sequentially washed with water (3 x100 mL). After the organic layer was separated and concentrated, the reaction mixture was purified by silica-gel chromatography (hexane/ethyl acetate) to give the product as a pale-yellow solid (1.559 g, 6.33mmol, 89.4% yield).

The synthetic route of 22236-08-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Zhaoda; Kil, Kun-Eek; Poutiainen, Pekka; Choi, Ji-Kyung; Kang, Hye-Jin; Huang, Xi-Ping; Roth, Bryan L.; Brownell, Anna-Liisa; Bioorganic and Medicinal Chemistry Letters; vol. 25; 18; (2015); p. 3956 – 3960;,
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Electric Literature of 22236-08-4, These common heterocyclic compound, 22236-08-4, name is 3-(Difluoromethoxy)aniline, its 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.

General procedure: A round bottom flask was charged under argon with aniline 3(1.0 equiv.), aldehyde 4 (1.0 equiv.), and tetronic acid 5 (1.0 equiv.) in2-pentanol or ethanol [0.3 M]. Reaction was refluxed (at 125 C or 80 C respectively) for 1 h, then the solvent was evaporated undervacuum and the crude product purified by recrystallization inethanol or by flash chromatography on silica gel

The synthetic route of 22236-08-4 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jeedimalla, Nagalakshmi; Flint, Madison; Smith, Lyndsay; Haces, Alberto; Minond, Dmitriy; Roche, Stephane P.; European Journal of Medicinal Chemistry; vol. 106; (2015); p. 167 – 179;,
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Synthetic Route of 22236-08-4, The chemical industry reduces the impact on the environment during synthesis 22236-08-4, name is 3-(Difluoromethoxy)aniline, I believe this compound will play a more active role in future production and life.

Method G6: N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl)quinazolin-4-amine (vi-s):_A mixture of 4-chloro-6-nitro-2-(pyrazin-2-yl)quinazoline (1.00 g, crude, 3.7 mmol, 1.0 eq.), 3-(difluoromethoxy)benzenamine (600 mg, 3.7 mmol, 1.0 eq.) and Et3N (1.00 g, 10 mmol, 3.0 eq) in THF (80 mL) was stirred at 75 C. for 18 h. After cooling, the volatiles were removed in vacuo and the residue was washed with H2O (100 mL×2). The solid was dried in vacuo to afford 1.40 g of N-(3-(difluoromethoxy)phenyl)-6-nitro-2-(pyrazin-2-yl)quinazolin-4-amine as a black solid (90.2% of two steps). LCMS m/z=411.0 (M+1) (Method A) (retention time=1.61 min)

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-(Difluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Suzuki, Masaki; Kondo, Kazumi; Kurimura, Muneaki; Valluru, Krishna Reddy; Takahashi, Akira; Kuroda, Takeshi; Takahashi, Haruka; Fukushima, Tae; Miyamura, Shin; Ghosh, Indranath; Dogra, Abhishek; Harriman, Geraldine; Elder, Amy; Shimizu, Satoshi; Hodgetts, Kevin J.; Newcom, Jason S.; US2015/307477; (2015); A1;,
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These common heterocyclic compound, 22236-08-4, name is 3-(Difluoromethoxy)aniline, its 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. name: 3-(Difluoromethoxy)aniline

To a stirred solution of rn-difluoromethoxy aniline, 8.20 mL (65.5 rnmol) in anhydrous tetrahydrofuran (100 mE) at -78 C was added n-butyl lithium, 33.0 mE (65.5 mmol, 2 M in hexane) dropwise maintaining the reaction temperature below -65 C during the addition. The reaction mixture was stirred for 1 hour at -78 C before rac-phenyl 4-{[(allyloxy)carbonyl]amino}-N-cyano-3-(3,4- dichlorophenyl)-4,5-dihydro- 1 H-pyrazole- 1 -carboximidate (intermediate 5), 10,0 g (21.8 rnmol) inanhydrous tetrahydrofuran (600 mE) was added dropwise maintaining the reaction temperature below-65 C. The reaction mixture was stirred for 2 hours at -78 C before slowly pouring over saturated ammonium chloride solution (700 mE). The crude product was extracted into ethyl acetate (700 mL) and the organic layers were combined and washed with brine solution (350 mE). The collected organic phase was dried over magnesium sulfate, filtered and the solvent evaporated to yield an off-whitecrude solid. The crude solid was precipitated from a minimum volume of ethyl acetate and filtered, washing with diethyl ether to yield rac-allyl [1- {N?-cyano-N- [3- (difluoromethoxy)phenyl]carbamimidoyl} -3 -(3 ,4-dichlorophenyl)-4,5-dihydro- 1 H-pyrazol-4- yl]carbamate, 7.6 g (67%) as a white solid. LCMS (method 2): Rt = 1.78 min. MS (ESI): [M + H]+ = 523.2

The synthetic route of 3-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; STELLFELD, Timo; STRESEMANN, Carlo; HILLIG, Roman; KOeHR, Silke; STOeCKIGT, Detlef; WEISKE, Joerg; BARAK, Naomi; CHRIST, Clara; TER LAAK, Antonius; BADOCK, Volker; (77 pag.)WO2016/166185; (2016); A1;,
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Adding a certain compound to certain chemical reactions, such as: 22236-08-4, name is 3-(Difluoromethoxy)aniline, 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 22236-08-4, HPLC of Formula: C7H7F2NO

Intermediate 2 rac- Allyl [3 -(4-chloro-3 -methylphenyl)- 1 – {N’ -cyano-N- [3 -(difluoromethoxy)phenyl] caxbamimidoyl } – 4.5-dihydro- 1 //-pyrazol-4-yl j carbamate To a stirred solution of m-difluoromethoxyaniline, 6.55 g (41.2 mmol) in tetrahydrofuran (60 mL) at – 70 to -60 C was added n-butyllithium, 21 mL (41.2 mmol, 2 M in hexanes) dropwise. The mixture was stirred for 1 hour at this temperature, at which time a solution of n/< -phenyl -4- { [(allyloxy)carbonyl]amino } -3 -(4-chioro-3 -methylphenyl)-N-cyano-4,5-dihydro- 1 H-pyrazoie- 1 - carboximidate (intermediate 10), 6.00 g (13.7 mmol) in tetrahydrofuran (100 mL) was added dropwise maintaining the temperature below -60 C. The reaction mixture was stirred for 2 hours and was then poured into saturated aqueous ammonium chloride solution (200 mL) and extracted with ethyl acetate (200 mL). The organic layer was washed with brine (200 mL), dried over magnesium sulfate and concentrated to give a yellow solid. The solid was slurried with diethyl ether (50 mL) and dried to give rac-allyl [3-(4-chloro-3-methylphenyl)-l-{N'-cyano-N-[3-(difluoromethoxy)phenyl]carbamimidoyl}- 4,5-dihydro- l/ -pyrazol-4-yl] carbamate, 6.20 g (90%) as a white solid. NMR (400 MHz, DMSO-d, ): delta [ppm] = 2.32 (s, 3H), 4.06 (dd, 1H), 4.35-4.53 (m, 311 ). 5.11 (d, 1H), 5.17 (dd, 1H), 5.49-5.60 (m, 1H), 5.84 (ddt, 1H), 6.98 (dd, 1H), 7.12-7.27 (m, 3H), 7.35-7.42 (m, 1H) 7.51 (d, 1H), 7.69 (dd, 1H), 7.83 (d, 1H), 8.15 (d, 1H), 9.70 (br s, 1H). LCMS (method 3): Rt = 1.79 min MS (ESI): [M + H j = 503.2 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-(Difluoromethoxy)aniline, other downstream synthetic routes, hurry up and to see. Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; STELLFELD, Timo; MOWAT, Jeffrey Stuart; STRESEMANN, Carlo; HILLIG, Roman; KOeHR, Silke; STOeCKIGT, Detlef; WEISKE, Joerg; HARTUNG, Ingo; BARAK, Naomi; CHRIST, Clara; TER LAAK, Antonius; BADOCK, Volker; CRAMPTON, Rosemary Helen; STEFANUTI, Ian; (194 pag.)WO2016/166186; (2016); A1;,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 22236-08-4, name is 3-(Difluoromethoxy)aniline, A new synthetic method of this compound is introduced below., Computed Properties of C7H7F2NO

0.429 g of 3-(difluoromethoxy)-aniline (2.7 mmol) were dissolved in 5 mL of pyridine. 1 g of 4-methyl-3-[4-(2,2,2-trifluoro-acetyl)-piperazin-1-yl]-benzenesulfonylchloride (2.7 mmol) were added slowly at room temperature. After stirring for 16 h at room temperature, the reaction mixture was evaporated several times after addition of toluene. The residue was dissolved in dichloromethane and washed several times with 5% aqueous ammonium chloride. The organic phase was then washed with saturated aqueous sodium chloride, dried over sodium sulphate, filtered, and the solvent evaporated. The crude product was purified via silica gel chromatography using dichloromethane/methanol (0-5%) to yield 0.63 g of product.

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; ABBOTT GMBH &amp;; CO. KG; ABBOTT LABORATORIES; HAUPT, Andreas; POHLKI, Frauke; DRESCHER, Karla; WICKE, Karsten; UNGER, Liliane; RELO, Ana-Lucia; BESPALOV, Anton; VOGG, Barbara; BACKFISCH, Gisela; DELZER, Juergen; ZHANG, Min; LAO, Yanbin; WO2010/125134; (2010); A1;,
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22236-08-4, 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 22236-08-4 as follows.

Reference Example 353-{[3-(Difluoromethoxy)phenyl]hydrazono}pentane-2,4-dione To a solution of 3-(difluoromethoxy)aniline (1000 mg, 6.25 mmol) in 10 mL of acetic acid and 2 mL of concentrated hydrochloride solution, sodium nitrite (518 mg, 7.50 mmol) in 4 mL of water was added dropwise at 0 C., and the mixture was stirred at 0 C. for 1 h. Then to the reaction mixture was added dropwise a solution of sodium acetate (1538 mg, 18.75 mmol) and acetylacetone (812 mg, 8.12 mmol) in 10 mL of ethanol and 6 mL of water. The mixture was stirred at room temperature overnight, filtered, washed with water, EtOH/H2O (1:1) and hexane, and dried to give 3-{[3-(difluoromethoxy)phenyl]hydrazono}pentane-2,4-dione (1500 mg, 89%).LCMS: m/z=271 [M++H].

According to the analysis of related databases, 3-(Difluoromethoxy)aniline, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Taniguchi, Takahiko; Kawada, Akira; Kondo, Mitsuyo; Quinn, John F.; Kunitomo, Jun; Yoshikawa, Masato; Fushimi, Makoto; US2010/197651; (2010); A1;,
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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. 22236-08-4, name is 3-(Difluoromethoxy)aniline, This compound has unique chemical properties. The synthetic route is as follows., 22236-08-4

General procedure: A two neck round bottom flask under argon equipped with acondenser was charged with aldehyde 4 (1.0 equiv.) and 4-chloroaniline 3l (1.1 equiv.) in 2-pentanol [0.3 M] and stirred atreflux for 2 h. The tetronic acid 5 (1.1 equiv.) in 2-pentanol (minimumamount) was then added at reflux. After another 10 min atreflux, the third component aniline 3 (1.0 equiv.) was added neat.The reaction mixture was refluxed for an additional 30 min. Allvolatiles were evaporated under vacuum and the crude product purified by recrystallization in ethanol or by flash chromatographyon silica gel

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Reference:
Article; Jeedimalla, Nagalakshmi; Flint, Madison; Smith, Lyndsay; Haces, Alberto; Minond, Dmitriy; Roche, Stephane P.; European Journal of Medicinal Chemistry; vol. 106; (2015); p. 167 – 179;,
Ether – Wikipedia,
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22236-08-4, name is 3-(Difluoromethoxy)aniline, 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. 22236-08-4

General procedure: Step-1:4-amino-2,6-dichloro pyrimidine: 2,4,6-trichloro pyrimidine (1.0 mmol) in ethanol (5 mL) was treated with an aromatic amine (1.1 mmol) in the presence of Na2CO3 (1.1 mmol) at rt. The mixture was stirred at reflux for 2-4 h until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, an equal volume of water was added with cooling. The resulting white precipitate was filtered, washed with water, and dried in vacuum over night to yield 4-substituted 2,6-dichloro pyrimidine. In case of no precipitation, ethanol was removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 4-amino-2,6-dichloro pyrimidines in 85-95% yield. Step-2: 2,4-diamino-6-chloropyrimidine: 4-amino-2,6-dichloro pyrimidine (1.0 mmol) prepared from the above procedure was treated with another aliphatic amine or aromatic amine (2.0 mmol) in the presence of DIEPA (5.0 mmol) in n-BuOH (5 mL) at rt. For an aliphatic amine the reaction mixture was stirred at rt for overnight. For an aromatic amine the reaction mixture was refluxed for 24-72 h or placed in microwave (150 C, 2-7 h) until completion of the reaction. The reaction progress was followed by TLC. After completion of the reaction, solvents were removed by rota vap., and the residue was dissolved in CH2Cl2. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography (EtOAc/hexane) to afford the 2,4-diammino-6-chloropyrimidines in 85-90% yield. Step-3: 2,4,6-triaminopyrimidine: 2,4-diamino-6-chloropyrimidine (1.0 mmol) prepared from the above procedure was treated with another suitable aliphatic amine or aromatic amine (3.0 mmol). For an aliphatic amine, 2,4-diamino-6-chloropyrimidine (1.0 mmol) was treated with aliphatic amine (3.0 mmol) and DIPEA (5.0 mmol) in n-BuOH (5 mL) and placed in microwave (150 C) for 3-7 h. After the completion of the reaction (monitored by TLC), solvents were removed and the residue was dissolved in EtOAc. The organic layer was washed twice with water, brine, dried (Na2SO4), filtered, and concentrated. The resulting crude was purified by column chromatography to afford the 2,4,6-triaminopyrimidines 90-95% yield. For aromatic amine; 2,4-diamino-6-chloropyrimidine (1.0 equiv) was dissolved in dioxane under argon and to that were added Pd2(dba)3 (10 mol %), Xantphos (10 mol %), aromatic amine (1.2 mmol), t-BuOK (1.2 mmol). The resulting solution was degassed with argon for 5 min and heated to 85 C for overnight. The reaction mixture was filtered through a pad of celite, washed with CH2Cl2 (2 ¡Á 10 mL) and the resulting filtrate was concentrated. The resulting crude was purified by flash column chromatography to yield 2,4,6-triaminopyrimidines in 90-95% yield.

Statistics shows that 22236-08-4 is playing an increasingly important role. we look forward to future research findings about 3-(Difluoromethoxy)aniline.

Reference:
Article; Sagi, Vasudeva Naidu; Liu, Tianyu; Lu, Xiaoying; Bartfai, Tamas; Roberts, Edward; Bioorganic and Medicinal Chemistry Letters; vol. 21; 23; (2011); p. 7210 – 7215;,
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