Category: 2106-02-7

These common heterocyclic compound, 2106-02-7, name is 2-Chloro-4-fluoroaniline, 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. Product Details of 2106-02-7

Into a 20-L 4-neck round flask was placed a solution of 2-chloro-4- fluorobenzenamine (1300 g, 8.82 mol, 1.00 equiv, 99%) in toluene (10 L), 4- methylbenzenesulfonic acid (3.1 g, 17.84 mmol, 99%), and hexane-2,5-dione (1222.5 g, 10.62 mol, 1.20 equiv, 99%). The resulting solution was heated to reflux for 1 h in an oil bath and cooled. The pH value of the solution was adjusted to 8 with sodium carbonate (1 mol/L). The resulting mixture was washed with 1×5000 mL of water and concentrated under vacuum. The crude product was purified by distillation and the fraction was collected at 140 0C to afford l-(2- chloro-4-fluorophenyl)-2,5-dimethyl-lH-pyrrole (1700 g, yield: 85%).

The synthetic route of 2-Chloro-4-fluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; ALIAGAS, Ignacio; GRADL, Stefan; GUNZNER, Janet; MATHIEU, Simon; RUDOLPH, Joachim; WEN, Zhaoyang; WENGLOWSKY, Steven Mark; WO2011/25947; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 2106-02-7, name is 2-Chloro-4-fluoroaniline, A new synthetic method of this compound is introduced below., Recommanded Product: 2106-02-7

In another 1L four-neck reaction flask, under the protection of nitrogen, 219.54 g of tetrahydrofuran was added in sequence.77.43g (0.532mol) 2-chloro-4-fluoroaniline, 0.73g (0.00532mol) zinc chloride, 0.29g (0.000532mol) (dppp)NiCl2, stirring, the reaction system is cooled to 10 ~ 15 C, dripping Add the 3,4-dichlorophenylmagnesium bromide Grignard reagent produced in step 1 to the system, keep the temperature at 10-15 C, add the dropwise time for 3 hours, add dropwise, and keep warm for 4 h.After the sampling and detection reaction was completed, dilute hydrochloric acid was added dropwise to the reaction liquid, the reaction was quenched, stirred for 10 min, allowed to stand, layered, and the organic layer was washed with a 5% sodium chloride solution.The mixture was allowed to stand for stratification, and the organic layer was added with activated carbon, heated to reflux, filtered while hot, and the filtrate was concentrated under reduced pressure to remove tetrahydrofuran.So far, the temperature was lowered to 20 to 25 C to obtain a white flake solid, which was 3′,4′-dichloro-5-fluoro-2-aminobiphenyl, and the solid was weighed to 123.4 g, and the yield was 90.6% (by 2- Chloro-4-fluoroaniline), purity (GC) ? 99.0%.

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; Lianhua Science And Technology (Shanghai) Co., Ltd.; Lianhua Technology Co., Ltd.; Liaoning Tian Yu Chemical Co., Ltd.; Hubei Jun Tai Pharmaceutical And Chemical Co., Ltd.; Fan Xiaobin; Guo Zhanghong; Jiang Peng; (18 pag.)CN105198682; (2018); B;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

2106-02-7, name is 2-Chloro-4-fluoroaniline, belongs to chlorides-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. Computed Properties of C6H5ClFN

Production of ethyl (3S)-3-{[(2-chloro-4-fluorophenyl)amino]sulfanyl}-3,6-dihydro-2H-pyran-4-carboxylate To a solution (400 mL) of ethyl (3S)-3-sulfanyl-3,6-dihydro-2H-pyran-4-carboxylate (14.5 g) in dichloromethane was added dropwise tert-butyl hypochlorite (10 mL) at -78C. After stirring for 30 min, 2-chloro-4-fluoroaniline (23 mL) was added dropwise at -78C. The reaction mixture was stirred for 1 hr, and the reaction was discontinued with 5% aqueous sodium sulfite solution (300 mL). After extraction with dichloromethane (300 mL), the extract was washed with water, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (hexane/ethyl acetate=15:1?5:1) to give the title compound as a crude product (20.0 g, 96.3 %ee). This product was crystallized from diisopropyl ether/hexane (120 mL, 1:5) to give the title compound (12.3 g, 62%) as white crystals. 1H-NMR (CDCl3) delta: 1.33 (3H, t, J = 7.2 Hz), 3.72-3.79 (2H, m), 4.20-4.46 (5H, m), 5.53 (1H, br s), 6.90-7.03 (3H, m), 7.54-7.59 (1H, m). enantiomeric excess: >99 %ee [column: CHIRALPAK AD (manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.), mobile phase: hexane/2-propanol = 97.5/2.5].

The synthetic route of 2106-02-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; KITAMOTO, Naomi; (26 pag.)EP2528598; (2016); B1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 2106-02-7, 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. 2106-02-7, name is 2-Chloro-4-fluoroaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Synthesis of2-chloro-N-(2-chloro-4-fluorophenyl)-5-methoxypyrimidin-4-amine [0431] To a stirred solution of 2, 4-dichloro-5-methoxypyrimidine (5 g, 27.93 mmol) in DMF (50 mL) under argon atmosphere were added sodium hydride (1.3 g, 55.86 mmol) and 2-chloro-4-fluoroaniline (4 g, 27.93 mmol) at 0 C. The reaction mixture was warmed to RT and stirred for 16 h. After consumption of the starting materials (monitored by TLC), the reaction was diluted with ice water (50 mL) to afford the solid which was filtered, washed with water and dried in vacuo to afford 2-chloro-N-(2-chloro-4-fluorophenyl)-5- methoxypyrimidin-4-amine (3.5 g, 44%) as an off-white solid. 1H-NMR (DMSO-< 5, 400 MHz): delta 9.10 (s, 1H), 7.92 (s, 1H), 7.61-7.55 (m, 2H), 7.29 (t, 1H), 3.93 (s, 3H); LCMS: 288.2 (M+); (column; X-Select CSH C-18 (50 3.0 mm, 3.5 mupiiota); RT 3.76 min. 5 mM Aq NH4OAc: ACN; 0.80 mL/min); TLC: 10% EtOAc:hexanes (R 0.5). 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, 2-Chloro-4-fluoroaniline, other downstream synthetic routes, hurry up and to see. Reference:
Patent; FORUM PHARMACEUTICALS INC.; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; MCRINER, Andrew, J.; WO2015/66697; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 2106-02-7, name is 2-Chloro-4-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C6H5ClFN

General procedure: The aniline (1 eq) was dissolved in 6 N HCl solution (10 mL/mmol of aniline) at room temperature and cooled up to 0 C, followed by addition of NaNO2 (1.2 eq) in small portions under stirring. After 10 min of stirring at same temperature, sodium azide (1.2 eq) was added to the reaction mixture. This mixture was further stirred at room temperature for 3 h. The reaction was worked up by extraction with chloroform. The organic layer was washed with brine solution and dried over Na2SO4. After evaporation of the solvent, the crude product (9a-e) was pure enough for further reactions. All azides were stored at -20 C.

According to the analysis of related databases, 2106-02-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Kant, Rama; Kumar, Dharmendra; Agarwal, Drishti; Gupta, Rinkoo Devi; Tilak, Ragini; Awasthi, Satish Kumar; Agarwal, Alka; European Journal of Medicinal Chemistry; vol. 113; (2016); p. 34 – 49;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2106-02-7, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 2106-02-7 name is 2-Chloro-4-fluoroaniline, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

Concentrated nitric acid (8.8 g, 91 mmol) was added drop wise over 30 min to a stirred solution of 2-chloro-4-fluoro-phenylamine (12 g, 82.3 mmol) in cone H2SO4 acid (100 mL) at -10 0C. The mixture was stirred at that temperature for 10 min. Then the reaction mixture was poured into cooled EtOAc, and ice water was added. The organic layer was separated and washed with brine and saturated NaHCO3 solution, dried (MgSO4) and concentrated in vacuo. Recrystallization (ethyl ether) provided 2-chloro-4-fluoro-5-nitroaniline (5.0 g, 32% yield). 1H NMR (400 MHz, DMSO-rftf): (57.59 (d, J= 11.2 Hz, 1 H)5 7.48 (d, J= 7.2 Hz, 1 H), 5.84 (s, 2 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-4-fluoroaniline, and friends who are interested can also refer to it.

Reference:
Patent; DECIPHERA PHARMACEUTICALS, LLC; WO2008/33999; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 2106-02-7, name is 2-Chloro-4-fluoroaniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Safety of 2-Chloro-4-fluoroaniline

[446] 2-chloro-4-fluoroaniline (1 g, 7 mmol) was added to concentrated sulfuric acid (15 mL) at Q0 C, followed by the addition of guanidine nitrate (875 mg, 7 mmol). The mixture was warmed to it and stirred for 2 h. Subsequently, the mixture was poured onto ice and neutralized with aqueous sodium hydroxide (4N) until the pH was 9. The mixture was diluted with EtOAc and water, the organic phase was isolated and the aqueous phase was extracted with additional EtOAc (2x). The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel (0% – 10% EtOAc/heptane) to afford 2-chloro- 4-fluoro-5-nitroaniline (A2) as light brown solid.

The synthetic route of 2106-02-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARIAD PHARMACEUTICALS, INC.; HUANG, Wei-Sheng; LI, Feng; DALGARNO, David, C.; GONG, Yongjin; ISHCHENKO, Alexey, V.; KOHLMANN, Anna; SHAKESPEARE, William, C.; WEST, Angela, V.; XU, Yongjin; YOUNGSAYE, Willmen; ZHANG, Yun; ZHOU, Tianjun; ZHU, Xiaotian; (444 pag.)WO2015/175632; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 2106-02-7, 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. 2106-02-7, name is 2-Chloro-4-fluoroaniline, This compound has unique chemical properties. The synthetic route is as follows.

Method FA mixture of the relevant substituted pyrazole-3-carboxylic acid (intermediate TV or IX5 1.0 mmol) and SOCl2 (10 mL) was stirred at 80 0C for 18 h. After cooling to rt the mixture was concentrated and the residue dried in vacuo. A mixture of the relevant arylamine (1.0 mmol), DMAP (12 mg, 0.10 mmol), DMF (0.5 mL) and pyridine (1 mL) was added. The mixture was stirred at 80 C for 21 h and concentrated in vacuo. The residue was purified by chromatography (EtO Ac/heptane).

The chemical industry reduces the impact on the environment during synthesis 2-Chloro-4-fluoroaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BIOLIPOX AB; WO2007/45868; (2007); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Related Products of 2106-02-7, These common heterocyclic compound, 2106-02-7, name is 2-Chloro-4-fluoroaniline, 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.

Example 99 i-^-Chloro^-fluorophenylJ^-^-chloro^-fluorophenylJmethyl^S- piperazinedione (E99)Methyl [[(2-chloro-4-fluorophenyl)methyl](2-oxoethyl)amino](oxo)acetate (0.29 g, 1.0 mmol, prepared as described earlier) and 2-chloro-4-fluoraniline (0.29 g, 2.0 mmol) were dissolved in 2% acetic acid/methanol (10ml) at room temperature. The mixture was stirred for 15 minutes before polymer-supported cyanoborohydride (0.98 g, 4.0 mmol) was added. The mixture was stirred at room temperature overnight, then filtered through an SCX cartridge (Varian, 5g) and the filtrate concentrated in vacuo. The residue was then dissolved in 1-butanol (1.5 ml) and heated to 200 0C by microwave irradiation for 1 hour. The mixture was concentrated in vacuo and purified by mass-directed automated HPLC to yield 1-(2-chloro-4-fluorophenyl)-4-[(2-chloro- 4-fluorophenyl)methyl]-2,3-piperazinedione (0.161 g). LC/MS [M+H]+ = 385, retention time = 2.78 min.

The synthetic route of 2106-02-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXO GROUP LIMITED; CHAMBERS, Laura Jane; DEAN, David Kenneth; MUNOZ-MURIEDAS, Jorge; STEADMAN, Jon Graham Anthony; WALTER, Daryl Simon; WO2010/125103; (2010); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 2106-02-7, name is 2-Chloro-4-fluoroaniline, A new synthetic method of this compound is introduced below., name: 2-Chloro-4-fluoroaniline

Lithium hexamethyldisilazide (22.9 ml, 22.9 mmol, 1 M solution in tetrahydrofuran) wasadded over 5 mm to solution of 2-chloro-4-fluoroaniline (1 .84 g, 12.6 mmol, Gas No 2106-02-7) in tetrahydrofuran (60 ml) at -780 and the mixt ure was stired at -780 for 1 h. A solution of ethyl 4-{[tert-butyl(dimethyl)silyl]oxy}- 1 -(2-ch loroethyl)cyclohexanecarboxylate (mixture of cis-/trans-isomers) (4.00 g, 11 .5 mmol) in tetrahydrofuran (60 ml) was added and the mixture was stirred for 2 h at -780 and the for 3 days at room temperature. For work-up, the reactionmixture was poured into a mixture of water and saturated sodium bicarbonate solution, extracteted with ethyl acetate (3x) and the combined organic phases were washed with brine, filtrated through a silicone filter and concentrated under reduced pressured. The residue was purified by flash chromatography (Snap Gartdidge, hexanes/ethyl acetate gradient) to give 8-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-chloro-4-fluorophenyl)-2-azaspiro[4.5]decan-1 -one in 2 fractions. Fraction 1 (1.88 g, isomer 1, conatains ca 2Omol%2-chloro-4-fluoroaniline) and fraction 2 (485 mg, isomer 2).

The synthetic route of 2106-02-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; EIS, Knut; ACKERMANN, Jens; WAGNER, Sarah; BUCHGRABER, Philipp; SUeLZLE, Detlev; HOLTON, Simon; BENDER, Eckhard; LI, Volkhart; LIU, Ningshu; SIEGEL, Franziska; LIENAU, Philip; BAIRLEIN, Michaela; VON NUSSBAUM, Franz; HERBERT,Simon; KOPPITZ, Marcus; (734 pag.)WO2016/177658; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics