Category: 458-50-4

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. 458-50-4, name is 4-Bromo-3-fluoroanisole, A new synthetic method of this compound is introduced below., Application In Synthesis of 4-Bromo-3-fluoroanisole

A mixture of 4-bromo-3-fluoro anisole (2.0 g, 9.75 mmol), methyl 3-methyl-4-(4,4,5,5- tetramethyl-1-3s2-dioxaborolan-2-yl)benzoate (2.8 g, 10.14 mmol), Cs2C03 (6.99 g, 21.46 mmol) and catalytic amount of Pd(PPh3)4 (1.13 g, 0.975 mmol) in dioxane (50 mL) was stirred at 80 °C overnight. The solvent was removed. Water was added. The mixture was extracted with CH2C12 (3 x 20 mL). Washed with brine and dried over Na2SC>4.The residue was purified by column chromatography on silica gel Biotage 40M, eluting with EtOAc/hexane (1:9) to give the title compound as a colorless solid.

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; MERCK SHARP & DOHME CORP.; LU, Zhijian; CHEN, Yi-Heng; SMITH, Cameron; LI, Hong; THOMPSON, Christopher, F.; SWEIS, Ramzi; SINCLAIR, Peter; KALLASHI, Florida; HUNT, Julianne; ADAMSON, Samantha, E.; DONG, Guizhen; ONDEYKA, Debra, L.; QIAN, Xiaoxia; SUN, Wanying; VACHAL, Petr; ZHAO, Kake; WO2012/58187; (2012); A1;,
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458-50-4, A common compound: 458-50-4, name is 4-Bromo-3-fluoroanisole, 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.

General procedure: To a solution of 2-bromo-4-fluorobenzonitrile (0.30 g, 1.5 mmol) and cyclopropanol (0.14 g, 2.4 mmol) in DMF (4 mL) wasadded Cs2CO3 (0.88 g, 2.7 mmol) in a 25 mL single-necked round-bottom flask. After that, themixture was stirred at 25 °C under nitrogen. After stirring for 4 h, the resulting mixture was dilutedwith H2O (30 mL) and extracted with MTBE (10 mL×3). Then the combined organic phase waswashed with saturated aqueous NaCl (10 mL×3) and dried over Na2SO4 for 0.5 h. After that, theorganic phase was filtered under reduced pressure and the filtrate was concentrated underreduced pressure to give product as a yellow sticky substance. Then a mixture of 30 mL MTBE and100 mL n-hexane was added to dissolve the yellow sticky substance. Subsequently, the solutionwas cooled for 30 minutes with the mixture of water and ethanol. Lastly, the solution was filteredunder reduced pressure and the filtrate was dried naturally to obtain desired product in 80.3percentyield (0.29g).

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, 4-Bromo-3-fluoroanisole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Jin, Hao; Gao, Zhuo; Zhou, Shaodong; Qian, Chao; Synlett; vol. 30; 8; (2019); p. 982 – 986;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 458-50-4,Some common heterocyclic compound, 458-50-4, name is 4-Bromo-3-fluoroanisole, molecular formula is C7H6BrFO, 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.

A degassed solution of 3-amino-furo[3,2-c]pyridine-2-carboxylic acid ethyl ester (206 g, 1.0 mmol), l-bromo-2-fluoro-4-methoxy-benzene (246 mg, 1.2 mmol), Pd2dba3 (46 mg, 0.050 mmol), Xantphos (58 mg, 0.10 mmol) and K3PO4 (254 mg, 1.2 mmol) in toluene (5 ml) was heated to 1100C then stirred for 18 hours. The reaction mixture was cooled to ambient temperature then diluted with EtOAc and filtered through a pad of celite. The filtrate was concentrated in vacuo to give a black oil. The oil was purified by flash chromatography (Si-SPE, MeOH: DCM, gradient 0: 100 to 10:90) to provide the title compound as a yellow oil (130 mg, 39percent). LCMS (method B): Rx = 2.93 min, M+H+ = 331.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Bromo-3-fluoroanisole, its application will become more common.

Reference:
Patent; GENENTECH, INC.; WO2008/24725; (2008); 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. 458-50-4, name is 4-Bromo-3-fluoroanisole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 4-Bromo-3-fluoroanisole

A mixture of tert-butyl ((3S,5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-1-(5-(2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamido)-1H-indol-4-yl)pyrrolidin-3-yl)carbamate (50 mg, 0.072 mmol), 1-bromo-2-fluoro-4-methoxybenzene (22.3 mg, 0.109 mmol), copper(I) iodide (2.1 mg, 10.9 mumol) and potassium phosphate, tribasic (32.3 mg, 0.152 mmol) was purged with N2 and treated with N,N-dimethylcyclohexane-1,2-diamine (6.2 mg, 0.043 mmol) in 0.5 mL toluene. The reaction mixture was further treated with 0.3 mL DMF and heated to 110 C. for 40 hrs. After cooling to r.t., the reaction mixture was diluted with water and EtOAc. The separated organic phase was washed with brine, dried over sodium sulfate and concentrated under vacuum. The crude product was dissolved in 1 mL THF and treated with 0.5 mL of TBAF solution (1.0 M in THF). The resulting mixture was stirred at r.t. for 1 hr, then diluted with water and EtOAc. The separated organic phase was washed with brine, dried over sodium sulfate and concentrated under vacuum. The crude was purified by flash chromatography (eluted with EtOAc) and the obtained product was then dissolved in 1 mL DCM and treated with 1 mL TFA. The resulting mixture was stirred at r.t. for 1 hr and purified with prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% TFA, at flow rate of 60 mL/min). LCMS calculated for C32H31F2N6O4 (M+H)+: m/z=601.2; found 601.4.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 458-50-4.

Reference:
Patent; Incyte Corporation; Hummel, Joshua; Nguyen, Minh; Sokolsky, Alexander; Vechorkin, Oleg; Ye, Qinda; Yao, Wenqing; (72 pag.)US2019/315717; (2019); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 458-50-4, name is 4-Bromo-3-fluoroanisole, A new synthetic method of this compound is introduced below., Safety of 4-Bromo-3-fluoroanisole

Step 2: 9-(2-Fluoro-4-methoxy-phenyl)-bicyclo[3.3.1]nonan-9-oll-Bromo-2-fluoro-4-methoxy-benzene (4.10 g, 20 mmol) was dissolved in THF (30 ml) and cooled to -78°C. To the solution was added n-BuLi (1.6 M in THF, 12.5 ml, 20 mmol) dropwise. The reaction mixture was stirred at -78°C for 20 min, after which bicyclo[3.3.1]nonan-9-one (2.76 g, 20 mmol) in THF (20 ml) was added dropwise. The reaction mixture was stirred at -78°C for 2.5 hours and quenched at the same temperature with aqueous NH4C1 solution. Water and EtOAc were added. The reaction mixture was extracted with EtOAc three times. The organic phase was washed with brine and dried (Na2S04). Silica gel chromatography (EtO Ac/heptane) provided 3.4 g of the title compound.Ci6H2iF02 (264.15), LCMS (EI+): 264.14 (M+).1H NMR (CDCI3, 300MHz), delta 7.41 (t, 1H), 6.55-6.71 (m, 2H), 3.80 (s, 3H), 2.61 (br. s, 1H), 2.39 (m, 2H), 1.49-2.17 (m, 12H).

The synthetic route of 458-50-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANOFI-AVENTIS; KOSLEY, Raymond Walter, Jr.; SHER, Rosy; NEUENSCHWANDER, Kent W.; GURUNIAN, Vieroslava; WO2011/34832; (2011); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 458-50-4, name is 4-Bromo-3-fluoroanisole, A new synthetic method of this compound is introduced below., Formula: C7H6BrFO

A mixture of 4-bromo-3-fluoro anisole (2.0 g, 9.75 mmol), methyl 3-methyl-4-(4,4,5,5- tetramethyl-1-3s2-dioxaborolan-2-yl)benzoate (2.8 g, 10.14 mmol), Cs2C03 (6.99 g, 21.46 mmol) and catalytic amount of Pd(PPh3)4 (1.13 g, 0.975 mmol) in dioxane (50 mL) was stirred at 80 °C overnight. The solvent was removed. Water was added. The mixture was extracted with CH2C12 (3 x 20 mL). Washed with brine and dried over Na2SC>4.The residue was purified by column chromatography on silica gel Biotage 40M, eluting with EtOAc/hexane (1:9) to give the title compound as a colorless solid.

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; MERCK SHARP & DOHME CORP.; LU, Zhijian; CHEN, Yi-Heng; SMITH, Cameron; LI, Hong; THOMPSON, Christopher, F.; SWEIS, Ramzi; SINCLAIR, Peter; KALLASHI, Florida; HUNT, Julianne; ADAMSON, Samantha, E.; DONG, Guizhen; ONDEYKA, Debra, L.; QIAN, Xiaoxia; SUN, Wanying; VACHAL, Petr; ZHAO, Kake; WO2012/58187; (2012); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 458-50-4, 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 458-50-4 as follows.

At 0 deg.C, 1-bromo-2-fluoro-4-methoxybenzene (5.00 g, 24.39 mmol) in sulfuric acid (20.0 mL) solution was added portionwise potassium nitrate (2.47 g, 24.39 mmol). The reaction mixture was stirred at 0 deg.C for 0.5 h. TLC (petroleum ether: ethyl acetate = 3: 1) indicated the reaction was complete. The reaction mixture was added to ice water (50.0mL) in the quenched (100mL × 2) and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and filtered, and concentrated to dryness under reduced pressure to give the title compound (5.55 g, 90% yield) as a white solid.

According to the analysis of related databases, 458-50-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Nanjing Mingde New Drug Research and Development Co. Ltd.; Qilu Pharmaceutical Co., Ltd.; Ding, Zhaozhong; Zhang, Minghui; Chen, Shuhui; Liu, Xile; Zhu, Yidong; Fan, Chuanwen; Zhao, Baoping; Zhang, Long; Chen, Dong; Yang, Yingying; Zheng, Qingmei; Zheng, Shansong; Wan, Haiwen; Hu, Jinqing; (93 pag.)CN105330698; (2016); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 458-50-4, These common heterocyclic compound, 458-50-4, name is 4-Bromo-3-fluoroanisole, 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.

Step A1, 1 -dimethylethyl 4-[2~fluoro~4-(methyloxy)phenyl]-3-oxo-1-piperazinecarboxylate A mixture of 1-Boc-3-oxopiperazine (500 mg, 2.497 mmol), 4-bromo-3- fluoroanisole (512 mg, 2.497 mmol), copper(l) iodide (23.78 mg, 0.125 mmol), frans-Nu,Nu’- dimethylcycIohexane-1 ,2-diamine (0.039 mL, 0.250 mmo.), and potassium carbonate (690 mg, 4.99 mmol) in 1 ,4-dioxane (10 mL) was heated at 120 °C for 3.5 days. The mixture was filtered through a pad of Celite and washed with EtOAc (50 mL). The filtrate was washed with saturated aqueous NH4CI (15 mL), brine (15 mL), dried ( gS04), filtered and concentrated. The crude was absorbed on silica gel and purified by silica gelchromatography (10-60percent EtOAc in hexanes) to give 1 ,1 -dimethylethyl 4-[2-fluoro-4- (methyloxy)phenyl]-3-oxo~1 -piperazinecarboxylate (581.9 mg, 1 .794 mmol, 72 percent) as white solid. MS(ESI) m/z: 325.3 (MH+).

Statistics shows that 4-Bromo-3-fluoroanisole is playing an increasingly important role. we look forward to future research findings about 458-50-4.

Synthetic Route of 458-50-4, A common heterocyclic compound, 458-50-4, name is 4-Bromo-3-fluoroanisole, molecular formula is C7H6BrFO, 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.

Into a 25-mL round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed (i-Pr) 2NH (1.26 g, 12.48 mmol, 1.25 equiv), tetrahydrofuran (7 mL). This was followed by the addition of n-BuLi (2.5M in hexane) (4.8 mL) dropwise with stirring at ?78¡ã C. The mixture was stirred for 1 h at ?78¡ã C. Then this solution was added to the solution a solution of 1-bromo-2-fluoro-4-methoxybenzene (2.04 g, 9.95 mmol, 1.00 equiv) in tetrahydrofuran (5 mL) at ?78 degree C. and stirred for 30 min, then I2 (3.048 g, 12.00 mmol, 1.2 equiv) was added. The resulting solution was stirred for 30 min at ?78¡ã C. in a liquid nitrogen bath. The reaction progress was monitored by GCMS. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2¡Á20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with petroleum ether. This resulted in 2.0 g (61percent) of 1-bromo-2-fluoro-3-iodo-4-methoxybenzene as a light yellow solid. Mass spectrum (GC, m/z): Calcd. for C7H5BrFIO, 330.9 (M). found 330.9

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; Janssen Pharmaceutica NV; Illig, Carl R.; Player, Mark R.; Zhang, Xuqing; US9067898; (2015); B1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 458-50-4, 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 458-50-4 as follows.

To a dry and N2 flashed flask was added 4-bromo-3-fluoroanisole (1.04 g, 5.07 mmol) in THF (6 mL) under N2. This was cooled to -78 ¡ãC, and n-BnLi (1.72 mL, 4.29 mmol) was added. The reaction was stirred at -78 ¡ãC for 30 min. The mixture above was added via cannula to a stirred solution of methyl 3-oxocyclobutane carboxylate (500 mg, 3.90 mmol) in dry Et20 (35 mL) at – 78 ¡ãC under N2. The reaction mixture was allowed to warm to room temperature and was stirred for 1 h. Satd aq. NH4C1 was added and the mixture was stirred until a clear solution resulted. This mixture was extracted with Et20 (3 x). The combined extracts were dried (MgS04) and concentrated in vacuo to give the crude product, which was purified by flash chromatography (Biotage Horizon, 40M, Si, -30 mL/min, 100percent hexanes for 260 mL, gradient to 40percent EtOAc in hexanes over 5184 mL) to afford methyl 3-(2-fluoro-4-methoxyphenyl)-3- hydroxycyclobutanecarboxylate (450 mg, 45 percent). NMR (500 MHz, CDC13): delta 7.32 (t, J= 8.9 Hz, 1 H); 6.69-6.63 (m, 2 H); 3.80 (s, 3 H); 3.74 (s, 3 H); 3.40 (s, 1 H); 3.03-2.93 (m, 2 H); 2.90-2.82 (m, 1 H); 2.67-2.61 (m, 2 H).

According to the analysis of related databases, 458-50-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LU, Zhijian; CHEN, Yi-Heng; SMITH, Cameron; LI, Hong; THOMPSON, Christopher, F.; SWEIS, Ramzi; SINCLAIR, Peter; KALLASHI, Florida; HUNT, Julianne; ADAMSON, Samantha, E.; DONG, Guizhen; ONDEYKA, Debra, L.; QIAN, Xiaoxia; SUN, Wanying; VACHAL, Petr; ZHAO, Kake; WO2012/58187; (2012); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem