Author: Jessica.F

These common heterocyclic compound, 1516-96-7, name is 5-Bromo-1,3-di-tert-butyl-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. COA of Formula: C15H23BrO

Production Example 7 of Optically Active AminoalcoholA 300 mL round-bottom four-neck flask equipped with a Dimroth condenser with a nitrogen introducing tube attached thereto, a thermometer, a magnetic rotator and a dropping funnel was heated under reduced pressure, nitrogen was then introduced into the flask, pressure in the flask was returned to normal pressure, and the flask was cooled to room temperature. After 1.99 g of magnesium and a minor amount of iodine were added to the flask, a small amount of a solution obtained by mixing 25.30 g of 4-methoxy-3,5-di-tert-butylbromobenzene and 119.0 mL of dehydrated tetrahydrofuran was added dropwise. The flask was heated, and it was confirmed that the Grignard reaction was initiated. Thereafter, the remaining solution was added dropwise over 30 minutes. The resulting mixture was refluxed for 1.5 hours. After the resulting reaction mixture was cooled to -10 C., 1.45 g of L-alanine methyl ester hydrochloride was added. The temperature of the resulting mixture was raised to room temperature, and the mixture was further refluxed for 3 hours. The resulting reaction mixture was cooled to 0 to 5 C. To the reaction mixture were added dropwise 70.0 mL of an aqueous saturated ammonium chloride solution, and further 20.0 mL of water. The resulting mixture was stirred at 20 C. for 12 minutes. The resulting mixture was extracted with 70.0 mL of diethyl ether three times. The resulting organic layers were mixed, and dried with anhydrous sodium sulfate. After sodium sulfate was removed by filtration, the resulting filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/9830/70) to obtain 3.32 g of a pale yellow solid of (S)-2-amino-1,1-di(4-methoxy-3,5-di-tert-butylphenyl)-3-methyl-1-butanol.1H-NMR (300 MHz, CDCl3, TMS standard)delta (ppm): 7.49 (2H, s), 7.34 (2H, s), 4.01 (1H, m), 3.86 (1H, brs), 3.67 (3H, s), 3.66 (3H, s), 1.44 (18H, s), 1.42 (18H, s), 1.22 (2H, br.s), 0.94 (3H, d)13C-NMR (75 MHz, CDCl3, TMS standard)delta (ppm): 158.58, 158.29, 143.46, 142.94, 141.10, 139.19, 124.95, 124.84, 79.58, 64.76, 53, 42, 36.58, 36.50, 32.91, 21.75, 18.07

The synthetic route of 5-Bromo-1,3-di-tert-butyl-2-methoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Masumoto, Katsuhisa; Yoshikawa, Kouji; US2011/166372; (2011); A1;,
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Synthetic Route of 29578-39-0,Some common heterocyclic compound, 29578-39-0, name is 1-Bromo-3-fluoro-5-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.

To a solution of 3-bromo-5-fluoroanisole (250 mg, 1.22 mmol, 1 equiv) in anhydrous THF was added granules of magnesium (32 mg, 1.28 mmol, 1.05 equiv) under nitrogen. The mixture was heated to 60 C for 2 h. After cooling down to room temperature, 6-bromopyridin-2-yl carboxaldehyde (271 mg, 1.47 mmol, 1.2 equiv) was added and the reaction mixture was stirred at 80 C overnight. The reaction was cooled to room temperature, quenched with brine and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated to dryness under vacuum. The product was purified by column chromatography (hexane/ethyl acetate 8:2) to afford the analytically pure compound in 21% yield (80 mg). C13H11BrFNO2; MW 312; 1H NMR (acetone-d6): delta 7.74 (t, J = 7.6 Hz, 1H), 7.64-7.61 (m, 1H), 7.47 (dd, J = 0.9 Hz, J = 7.2 Hz, 1H), 6.92-6.90 (m, 1H), 6.81 (ddd, J = 0.6 Hz, J = 1.3 Hz, J = 9.1 Hz, 1H), 6.59 (dt, J = 2.5 Hz, J = 10.7 Hz, 1H), 5.77 (d, J = 4.7 Hz, 1H), 5.35 (d, J = 4.7 Hz, 1H), 3.79 (s, 3H); 13C NMR (acetone-d6): delta 165.8, 165.3, 140.8, 127.5, 120.3, 109.4, 106.1, 105.9, 101.0, 100.8, 75.8, 56.0; LC/MS m/z: 312-314 (M + H)+.

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-3-fluoro-5-methoxybenzene, its application will become more common.

Reference:
Article; Wetzel, Marie; Gargano, Emanuele M.; Hinsberger, Stefan; Marchais-Oberwinkler, Sandrine; Hartmann, Rolf W.; European Journal of Medicinal Chemistry; vol. 47; 1; (2012); p. 1 – 17;,
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Related Products of 887581-09-1,Some common heterocyclic compound, 887581-09-1, name is (2-Bromo-5-methoxyphenyl)methanamine, molecular formula is C8H10BrNO, 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: To a magnetically stirred solution of the formyl ester 8a (400 mg, 1.6 mmol) in CH2ClCH2Cl (5 mL) at room temperature, were added sequentially 2-bromobenzyl amine 3a (420 mg, 2.2 mmol) and AcOH (0.14 mL, 2.4 mmol) followed by refluxing of the mixture for 12 h. After cooling, the reaction mixture was treated with aqueous NaHCO3 solution and extracted with ethyl acetate (3 ¡Á 12 mL). The combined organic layers were washed with brine, dried (Na2SO4), and filtered. Concentration of the filtrate followed by flash chromatography (ethyl acetate/hexane, 1:6 to 2:3) furnished the cyclic enamide 9aa (480 mg, 80%) as brown viscous oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (2-Bromo-5-methoxyphenyl)methanamine, its application will become more common.

Reference:
Article; Satyanarayana, Gedu; Maier, Martin E.; Tetrahedron; vol. 68; 6; (2012); p. 1745 – 1749;,
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Electric Literature of 1535-75-7, 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. 1535-75-7, name is 2-(Trifluoromethoxy)aniline belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

General procedure: Representative procedure for the 2-methyl-N,4-diphenylquinoline-3-carboxamide (Entry 22, Table 1): To the magnetically stirred solution of KOt-Bu (2 mmol) in THF (6 mL) at rt, was added methyl 2-methyl-4-phenylquinoline-3-carboxylate 3a (0.277 g, 1 mmol) followed by addition of aniline (0.093 mL, 1 mmol, 1 equiv) and the mixture was allow to stirred at rt until the completion of reaction (5 h, monitored by TLC) . After completion of reaction THF evaporated under rotary vacuum evaporation, crude reaction mixture was extracted with EtOAc (3 ¡Á 5 mL) and H2O (5 mL). The combined EtOAc extracts were dried (anh Na2SO4), filtered, and the filtrate was concentrated under rotary vacuum evaporation. The crude product was adsorbed on silica gel (230-400 mesh size, 500 mg), charged on to a flash chromatography column of silica-gel (230-400 mesh size, 2.5 g), and eluted with hexane-EtOAc (90:10) to obtain analytically pure 2-methyl-N,4-diphenylquinoline-3-carboxamide, 5a as white solid (0.219 g, 65%);

The synthetic route of 2-(Trifluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Article; Tanwar, Babita; Kumar, Asim; Yogeeswari, Perumal; Sriram, Dharmarajan; Chakraborti, Asit K.; Bioorganic and Medicinal Chemistry Letters; vol. 26; 24; (2016); p. 5960 – 5966;,
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Reference of 352-67-0, 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. 352-67-0, name is 1-Fluoro-4-(trifluoromethoxy)benzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A. 1 -Fluoro-2-nitro-4-trifluoromethoxy-benzene and 4-Fluoro-2-nitro-1 – trifluoromethoxy-benzeneTo a mixture of 1-fluoro-4-trifluoromethoxy-benzene (31.57 g, 0.18 mol) in cone. H2SO4 (100 ml_) at 0C is added cone. HNO3 (30 ml_) dropwise over a 10 min period. After the mixture is stirred at 0 C for 1 h, it was poured into ice. The mixture is extracted with EtOAc. The organic extract is washed with H2O (3x) and brine, dried over MgSO4, filtered, and concentrated in vacuo to yield 38 g (96%) of the product as a mixture of 1 -fluoro-2-nitro-4-trifluoromethoxy-benzene and 4-fluoro-2-nitro-1 – trifluoromethoxy-benzene (-30/70, based upon 19F NMR). 1H NMR (CDCI3): delta 8.00- 7.90 and 7.80-7.65 (m, 1 H), 7.60-7.25 (m, 2H); 19 F NMR (CDCI3) delta -57.59 and -58.11 (s, 3F), -109.07 and -117.90 (t, J = 6.2 and d, J = 6.2, 1 F).

The synthetic route of 1-Fluoro-4-(trifluoromethoxy)benzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SANOFI-AVENTIS; CHOI-SLEDESKI, Yong-Mi; GARDNER, Charles, J.; LIANG, Guyan; POLI, Gregory, B.; SHUM, Patrick, Wai-Kwok; STOKLOSA, Gregory, T.; ZHAO, Zhicheng; WO2011/22449; (2011); 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. 658-89-9, name is 4-(Trifluoromethoxy)benzene-1,2-diamine, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 4-(Trifluoromethoxy)benzene-1,2-diamine

To a mixture of 4-(trifluoromethoxy)benzene-1,2-diamine (0.1 g, 521 imol, 1 eq) in 2 mL of dichloromethanecooled to 0C was added methyl 2,2,2-trichloroethanimidate (119 mg, 676 imol, 1.3 eq), TFA(148 mg, 1.3 mmol, 2.5 eq) successively. The mixture was stirred at 25C for 12 hours underN2 atmosphere. The mixture was filtered and the filtrate was purified by prep-TLC (Si02,eluting with petroleum ether: ethyl acetate = 2:1) to give a 0.1 g of compound J-3 (44% yield,TFA salt) as a yellow solid.

According to the analysis of related databases, 658-89-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AQUINNAH PHARMACEUTICALS, INC.; BURNETT, Duane, A.; VACCA, Joseph, P.; (310 pag.)WO2018/119395; (2018); A1;,
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Electric Literature of 2398-37-0, A common heterocyclic compound, 2398-37-0, name is 1-Bromo-3-methoxybenzene, molecular formula is C7H7BrO, 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.

The advantageous effect of adding zinc chloride to an amination reaction was demonstrated in the amination reaction of 3-bromoanisole. the results of which are summarized in Table 10. When 3-bromoanisole was reacted under the standard lithium amide amination conditions, using lithium amide (10 eq.) in the presence of (CyPF-^-Bu)PdCl2 (1 mol%) in DME gave a complicated mixture of products was obtained (Table 10, Entry 1). When conducted in the presence of zinc chloride and TMEDA, however, the reaction could successfully gave the desired monoarylation product, 3-methoxyaniline, although at high concentrationsN,N-dimethyl-3-methoxyaniline was formed in a significant amount as a by- product (Table 10, Entries 3 and 4). Under optimized conditions (Table 10, Entries 8 and 9), 3-methoxyaniline was formed selectively in good yield.

The synthetic route of 2398-37-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; YALE UNIVERSITY; WO2007/109365; (2007); A2;,
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589-10-6, name is (2-Bromoethoxy)benzene, 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. Application In Synthesis of (2-Bromoethoxy)benzene

Cesium carbonate (0.490 g, 1.5 mmol) and 1-(2-bromoethoxy)benzene (0.261 g, 1.30 mmol) were added to a solution of (E)-ethyl 3-(1H-pyrazol-4-yl)acrylate (0.167 g, 1 mmol) in ACN (8 mL) at room temperature. The suspension was stirred overnight at 80 C. The reaction mixture was then cooled down to room temperature and the precipitated solids were filtered off. The filtrate was concentrated and purified by silica gel column chromatography using a gradient of 0-60% of EtOAc in hexanes to provide the title compound (0.203 g, 71%) as a colorless oil. ES+(M+H)+287

The synthetic route of 589-10-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Jacques, Vincent; Rusche, James R.; Peet, Norton P.; Singh, Jasbir; US2013/317003; (2013); A1;,
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Application of 106854-77-7, These common heterocyclic compound, 106854-77-7, name is 1-Bromo-4-(2,2,2-trifluoroethoxy)benzene, 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.

1-BROMO-4- (2, 2, 2-trifluoroethoxy) benzene (14.5 g, 57 mmol) was dissolved in toluene (250ML) under an argon atmosphere. tert-Butyl PIPERAZINE-1-CARBOXYLATE (12.7 g, 68 mmol), sodium tert-butoxide (7.6 g, 79.5 mmol) rac-2,2′-bis (DIPHENYLPHOSPHINO)-1, 1 -BINAPHTHYL (200 mg, 0.32 mmol) and tris (dibenzylideneacetone) dipalladium (0) (200 mg, 0.2 mmol) were added and the reaction heated to 80 C for 4 hours. The mixture was then cooled and filtered through Celite to yield crude tert-butyl 4- [4- (2, 2,2-trifluoroethoxy) phenyl] piperazine-1- carboxylate (32.47 g). H NMR (400 MHZ, CDC13) : 8 6.90 (4 H, s), 4.30 (2 H, q), 3.60 (4 H, m), 3.05 (4 H, m), 1.45 (9 H, s); 7TL/Z (ES) 305 (MHS- BU).

Statistics shows that 1-Bromo-4-(2,2,2-trifluoroethoxy)benzene is playing an increasingly important role. we look forward to future research findings about 106854-77-7.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2005/822; (2005); 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 458-52-6 as follows. Recommanded Product: 2-Fluoro-4-methoxyaniline

A mixture of (+-)-4-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl-amino]-2-methylsulfanyl-pyrimidine-5-carbaldehyde (171 mg, 0.46 mmol) (from Example 13a supra), p-toluenesulfonic acid mono-hydrate (10 mg) (Aldrich) and 2-fluoro-4-methoxyaniline (79 mg, 0.56 mmol) (from Example 14a supra) in benzene (30 ML) was refluxed in a Dean-Stark apparatus for 8 hours.The mixture was then cooled and partitioned between ethyl acetate and saturated aqueous potassium carbonate.The organic layer was collected, dried over sodium sulfate, filtered and concentrated.The residue was dissolved in anhydrous tetrahydrofuran (50 ML) and to this solution was added in small portions lithium aluminum hydride (53 mg, 1.40 mmol) (Aldrich) at 0¡ã C. The slurry was allowed to slowly warm up to room temperature and after overnight stirring was poured slowly into a vigorously stirred mixture of ethyl acetate and saturated aqueous potassium sodium tartrate solution.The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that upon purification by silica gel column chromatography with a 0-60percent ethyl acetate in hexanes gradient gave (+-)-[3-trans-(tert-butyl-dimethyl-silanyloxy)-cyclopentyl]-{5-[(2-fluoro-4-methoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl}-amine as a colorless viscous oil. (Yield 187 mg, 83percent). HRMS m/z calculated for C24H37FN4O2SSi [M+H]+: 493.2464. Found: 493.2472.

According to the analysis of related databases, 458-52-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Chen, Yi; Dermatakis, Apostolos; Liu, Jin-Jun; Luk, Kin-Chun; Michoud, Christophe; Rossman, Pamela Loreen; US2004/204427; (2004); A1;,
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