Category: 450-88-4

Application of 450-88-4, A common heterocyclic compound, 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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.

Intermediate Example Int20.014-(4-bromo-3-methoxyphenoxy)-1-methylpiperidineTo a stirred suspension of sodium hydride (1.76 g; 60% w/w sodium hydride in oil) in DMF (55 mL) was added 1-methylpiperidin-4-ol (3.37 g) at 0 C. The mixture was stirred at r.t. for 30 min. 1-bromo-4-fluoro-2-methoxybenzene (3.0 g) was added and the mixture was stirred at 100 C for 1 h. Water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Aminophase-silica-gel chromatography gave 3.65 g of the title compound.

The synthetic route of 450-88-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER INTELLECTUAL PROPERTY GMBH; SCHULZE, Volker; KOSEMUND, Dirk; WENGNER, Antje, Margret; SIEMEISTER, Gerhard; STOeCKIGT, Detlef; LIENAU, Philip; BRIEM, Hans; WO2012/160029; (2012); A1;,
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Reference of 450-88-4,Some common heterocyclic compound, 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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.

8.4 g of 1-bromo-4-fluoro-2-methoxybenzene obtained by Production example 89 was dissolved in 200 mL of dichloromethane, added under nitrogen atmosphere at 0C with 21 mL of titanium tetrachloride and 5.6 mL of dichloromethylmethylether, and stirred at room temperature for 4 hours and 30 minutes. The reaction solution was slowly poured into ice water, and extracted twice with diethyl ether. The organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate and water, and then dried over magnesium sulfate. The solvent was evaporated, to afford 9.44 g of the title compound as white crystals.1H-NMR ( 400 MHz, CDCl3 ) delta 3.97 ( 3H, s ), 6.67 ( 1H, d, J = 12.0 Hz ),8.05 ( 1H, d, J = 7.6 Hz ), 10.15 ( 1H, s )

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-4-fluoro-2-methoxybenzene, its application will become more common.

Reference:
Patent; Eisai Co., Ltd.; EP1510516; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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 450-88-4, Recommanded Product: 1-Bromo-4-fluoro-2-methoxybenzene

1-Bromo-4-fluoro-3-methoxybenzene (773 mg, 3.77 mmol) and bis(pinacolato)diboron (1.24 mg, 4.90 mmol) were dissolved in dioxane (10 mL), and anhydrous potassium acetate (1.11 mg, 11.31 mmol) and [1,1′-bis (diphenylphosphino)ferrocene]dichloropalladium.dichloromethane (276 mg, 0.377 mmol) were added. Under nitrogen gas atmosphere, the mixture was heated to 80 C. and stirred for 16 hours. After cooling to room temperature, the mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel TLC preparative plate (petroleum ether: ethyl acetate=1:1) to give compound 27-a (600 mg, yield 63%). 1H-NMR (400 MHz, CDCl3) delta: 7.65 (t, J=8.0 Hz, 1H), 6.55-6.66 (m, 2H), 3.82 (s, 3H), 1.34 (s, 12H) ppm

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, 1-Bromo-4-fluoro-2-methoxybenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GUANGZHOU MAXINOVEL PHARMACEUTICALS CO., LTD.; XU, Zusheng; ZHANG, Nong; WANG, Tinghan; SUN, Qingrui; WANG, Yuguang; (90 pag.)US2018/208604; (2018); A1;,
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Related Products of 450-88-4, These common heterocyclic compound, 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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.

A mixture of 1 -bromo-4-fluoro-2-methoxybenzene (CAS No. [450-88-4]; 10.0 g, 48.8 mmol) in concentrated sulfuric acid (50 mL) was cooled to 0 C and treated dropwise with a freshly prepared mixture of fuming nitric acid (1.05 eq., 2.1 mL, 51 mmol) and concentrated sulfuric acid (1.85 eq., 4.8 mL, 90 mmol). The reaction mixture was stirred at 0 C for 30 minutes and poured in small portions on ice water. The formed precipitate was filtered off, washed with cold water and kept. The filtrate was extracted with ethyl acetate and the organic layer combined with the isolated precipitate. The organic layer was dried with sodium sulfate and concentrated in vacuo. The obtained material was purified by flash chromatography (Si02-hexane/ ethyl acetate) to give the title compound (5.88 g, 44%).1H-NMR (400MHz, DMSO-de): delta [ppm] = 4.00 (s, 3H), 7.44 (d, 1 H), 8.40 (d, 1 H).UPLC- MS (ESI-): [M – H] = 248/250; R, = 1.17 min (Br isotope pattern; Method E).

The synthetic route of 450-88-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; PANKNIN, Olaf; RING, Sven; ZIMMERMANN, Katja; NEUHAUS, Roland; (153 pag.)WO2017/9325; (2017); 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. 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C7H6BrFO

a) 3-Bromo-6-fluoro-2-methoxybenzoic acid I45 To a solution of diisopropylamine (5.4 g, 53.7 mmol) in THF (150 ml.) at -78 C under N2 was added n-BuLi (2.5 M solution in hexanes, 23.4 ml_, 58.5 mmol) dropwise and the mixture was stirred at -78 C for 1 h. The resulting mixture was added dropwise to a solution of 1-bromo-4-fluoro-2-methoxybenzene (10.0 g, 48.8 mmol) in THF (50 ml.) at -78 C and stirring was continued for 90 min. C02 was bubbled through the mixture for 20 min with stirring at -78 C, then allowed to warm to RT and stirred for 15 min. The reaction mixture was adjusted to pH=1 with HCI and the mixture was diluted with water and extracted with DCM (500 ml_). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (DCM/MeOH = 100/1 to 30/1) to give the title compound (8.0 g, 66%) as a colorless oil. LCMS-D: Rt2.12 min; m/z 248.9/250.9 [M+H]+.

According to the analysis of related databases, 450-88-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CTXT PTY LIMITED; STUPPLE, Paul, Anthony; LAGIAKOS, Helen, Rachel; MORROW, Benjamin, Joseph; FOITZIK, Richard, Charles; HEMLEY, Catherine, Fae; CAMERINO, Michelle, Ang; BOZIKIS, Ylva, Elisabet, Bergman; WALKER, Scott, Raymond; (321 pag.)WO2019/243491; (2019); 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 450-88-4 as follows. Quality Control of 1-Bromo-4-fluoro-2-methoxybenzene

General procedure: Example 3Tandem Borylation/Dehalogenation of 1-Chloro-4-fluoro-3-Substituted- and 1-Bromo-4-fluoro-3-Substituted BenzenesTandem borylation/dehalogenation was also investigated as a strategy for the ortho-borylation of arenes that are substituted with an electron-withdrawing group. The scheme below illustrates the tandem borylation/dehalogenation methodology which was investigated. As discussed above, in the case of arenes that are substituted with an electron-withdrawing group, iridium-catalyzed C-H activation-borylation of the arene is typically governed by steric effects. In tandem borylation/dehalogenation, the substrate can include an electron-withdrawing group and a sacrificial atom (e.g., a halogen such as Cl or Br) positioned para to the electron-withdrawing group, so as to sterically hinder attack of the iridium catalyst at the otherwise sterically favored position meta to the electron-withdrawing group. As a result, iridium-catalyzed C-H activation-borylation of the arene exclusively generates the ortho-borylated (electronic) product. Subsequent dehalogenation can afford exclusively the desired electronic product.[0337] General Procedure for Borylation [0338] In a nitrogen atmosphere glovebox B2Pin2 (140 mg, 0.55 mmol) was weighed into a 20 mL vial containing a magnetic stir bar. [Ir(OMe)cod]2 (6.6 mg, 0.02 mmol) and 4,4?-di-tert-butyl-2,2?-dipyridyl ligand (5.4 mg, 0.02 mmol) were weighed into two separate test tubes, each being diluted with THF (2 mL). The [Ir(OMe)cod]2 solution was transferred into the 20 mL vial containing B2Pin2. This mixture was stirred until a golden yellow clear solution was obtained. The solution containing ligand was transferred into the vial, and the mixture was stirred until it became a dark brown color solution. The substrate (1 mmol) was added to the vial, which was then sealed. The reaction mixture stirred for 24 h at rt, after which the vial was removed from the glovebox. The reaction mixture was passed through a short plug of silica eluting with a 10:1 hexane/EtOAc solution (2¡Á10 mL). The volatiles were removed by rotary evaporation affording the product, which was characterized using standard methodologies. 1-Bromo-4-fluoro-2-methoxybenzene was borylated using the general procedure described above. After workup, a white solid was obtained (0.313 g, 95%): mp 104-105 C.; 1H NMR (500 MHz, CDCl3) delta 7.89 (d, J=6.5 Hz, 1H), 6.61 (d, J=11.0 Hz, 1H), 3.72 (s, 3H), 1.35 (s, 12H); 13C NMR (125 MHz, CDCl3) delta 167.6 (d, J=251.2 Hz), 159.5 (d, J=11.4 Hz), 140.2 (d, J=10.4 Hz), 108.3 (d, J=22.7 Hz), 105.9 (d, J=2.9 Hz), 83.9, 56.4, 24.8; 19F NMR (470 MHz, CDCl3) delta 100.4; 1113 NMR (160 MHz, CDCl3) delta 29.5 (br s).

According to the analysis of related databases, 450-88-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Smith, III, Milton R.; Maleczka, JR., Robert E.; Li, Hao; Jayasundara, Chathurika; Oppenheimer, Jossian; Sabasovs, Dmitrijs; US2015/65743; (2015); 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. 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, A new synthetic method of this compound is introduced below., Recommanded Product: 450-88-4

Step B: 4-fluoro-2-methoxybenzonitrile: To a solution of 1-bromo-4-fluoro-2-methoxybenzene(25 g, 0.12 mol) in 250 mL ofDMF was added Zn(CN)2 (28.6 g, 0.240 mol) and Pd(PPh3)4 (7.05g, 6.10 mmol) at one portion and the reaction was charged with Ar and heated to 100 C for 10 hours. Then the reaction was poured into IL ofEtOAc and filtered through a kieselguhr pad.The filtrate was washed with water, brine, dried and concentrated to solid, which was purified bysilica gel column to give 4-fluoro-2-methoxybenzonitrile.

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.; PASTERNAK, Alexander; BLIZZARD, Timothy; CHOBANIAN, Harry; DE JESUS, Reynalda; DING, Fa-Xiang; DONG, Shuzhi; GUDE, Candido; KIM, Dooseop; TANG, Haifeng; WALSH, Shawn; PIO, Barbara; JIANG, Jinlong; WO2013/28474; (2013); A1;,
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Synthetic Route of 450-88-4,Some common heterocyclic compound, 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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.

Reference Example 29 (1) In 15 ml of N, N-dimethylformamide were dissolved 3.94 g of [2-BROMO-5-FLUOROPHENOL] and 1.62 ml of methyl iodide, slowly added thereto was 5.08 g of potassium carbonate under ice-cooling. The mixture was stirred at room temperature for 3 hours. After insoluble matters were removed by filtration, distilled water was added to the filtrate, and the mixture was extracted with diethyl ether and washed with saturated brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography- (hexane : ethyl acetate=19: [1-9] : 1), to give 4.10 g of [1-BROMO4-FLUORO-2-] methoxybenzene. MS (m/z): 204/206 [(M++L) O] (2) To 7 ml of tetrahydrofuran were added 486 mg of magnesium and trace of iodine, and dropped thereto was a solution of 4.10 g of the compound of the above [(1)] in 16 ml of tetrahydrofuran, to prepare Grignard reagent. To the solution, a solution of 1.96 g of 4-methoxypyridine in 7 ml of tetrahydrofuran was added dropwise under nitrogen atmosphere [AT-60C] or below. Subsequently, a solution of 3.75 g of benzyl chloroformate in 18 ml of tetrahydrofuran was added dropwise, and the mixture was stirred for 3 hours. The temperature of the mixture was raised to room temperature, and 40 ml of a 5% aqueous citric acid solution was added thereto. The mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate=2: [1-1] : 2), to give 3.15 g of [1-BENZYLOXYCARBONYL-2- (4-FLUORO-2-METHOXYPHENYL)-4-OXO-] 3,4-dihydro-2H-pyridine. MS (m/z): 356 [[M++1]] (3) In a mixed solution of 79 ml of ethanol and 6 ml of tetrahydrofuran was dissolved 3.15 g of the compound of the above (2), and added thereto was 706 mg of sodium borohydride and the mixture was stirred at room temperature for 6 hours. The reaction mixture was concentrated and distilled water was added to the residue. The mixture was extracted with chloroform, and the organic layer was dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform: acetone=19: [1-9] : 1), to give 1.62 g of [1-BENZYLOXYCARBONYL-2- (4-FLUORO-2-] methoxyphenyl)-4-hydroxypiperidine. MS (m/z): 360 [[M++1]] (4) In 20 ml of toluene was dissolved 1.62 g of the compound of the above (3), added thereto was 876 mg of 1, [1′-] carbonyldiimidazole and the mixture was stirred at [60C] for an hour. Added thereto was 1.09 ml of ethanolamine, and the mixture was stirred at [60C] for 6 hours. To the reaction mixture was added distilled water and the mixture was extracted with chloroform. The organic layer was dried and concentrated. The residue was purified by silica gel column chromatography (chloroform: acetone=4: [1-1] : 1), to give 1.81 g of [1-BENZYLOXYCARBONYL-2- (4-FLUORO-2-METHOXYPHENYL)-4- (2-] hydroxyethylaminocarbonyloxy) piperidine. MS (m/z): 447 [[M++L]] [(5)] In 20 ml of methanol was dissolved 1.81 g of the compound of the above (4), and added thereto was 90 mg of 10% palladium-carbon, and the mixture was stirred at room temperature for an hour under hydrogen atmosphere. After insoluble matters were removed by filtration, the filtrate was concentrated. To the residue was added diethyl ether and precipitates were collected by filtration, to give 1.30 g of [2- (4-FLUORO 2-METHOXYPHENYL)-4- (2-] hydroxyethylaminocarbonyloxy) piperidine as shown in Table 134 below.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-4-fluoro-2-methoxybenzene, its application will become more common.

Reference:
Patent; TANABE SEIYAKU CO., LTD.; WO2003/99787; (2003); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 450-88-4, These common heterocyclic compound, 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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.

15 g of 1-bromo-4-fluoro-2-methoxybenzene obtained by Production example 89 was dissolved in 150 mL of 1-methyl-2-pyrrolidone, added with 9.9 g of copper cyanide (I), and stirred at 180C for 5 hours. After allowing to cool, the reaction solution was poured into 500 mL of 14% ammonia aqueous solution, stirred for 45minutes, then added with 150 mL of diethyl ether, and stirred for another 10 minutes. After filtering off the insoluble substances through Celite, the solution was extracted with diethyl ether. The organic layer was washed with diluted aqueous ammonia, 5N hydrochloric acid, water and saturated brine, and dried over magnesium sulfate. The solvent was evaporated, to afford 10.1 g of the title compound as white crystals.1H-NMR ( 400 MHz, CDCl3 ) delta 3.93 ( 3H, s ), 6.67 – 6.74 ( 2H, m ), 7.54 ( 1H, dd, J = 6.0, 8.4 Hz )

The synthetic route of 450-88-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Eisai Co., Ltd.; EP1510516; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

450-88-4, The chemical industry reduces the impact on the environment during synthesis 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, I believe this compound will play a more active role in future production and life.

To a stirred solution of 1 -bromo-4-fluoro-2-methoxybenzene (4.0 g) in DMF (40 mL) was added sodium methanethiolate (2.76 g). The mixture was stirred at room temperature for 30 minutes and at 85 C for 2 h. Water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Silica gel chromatography gave 280 mg of the title compound. 1H-NMR (400MHz, DMSO-d6): delta [ppm] = 2.46 (s, 3H), 3.82 (s, 3H), 6.74 (dd, 1 H), 6.91 (d, 1 H), 7.44 (d, 1 H).

The chemical industry reduces the impact on the environment during synthesis 1-Bromo-4-fluoro-2-methoxybenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; SCHULZE, Volker; MAIS, Franz-Josef; WO2014/9219; (2014); A1;,
Ether – Wikipedia,
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