Author: Jessica.F

25245-34-5, name is 2-Bromo-1,4-dimethoxybenzene, 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. category: ethers-buliding-blocks

25 mL single neck flask was charged with 2-bromo-1,4-dimethoxybenzene (1.0 g, 4.6 mmol), AcOH (5 mL),Then slowly add HNO3 (0.4 mL) dropwise,A large number of yellow solid solution was precipitated,After 0.5h,filter,Rinse the residue with plenty of water,Finally dried in a vacuum oven,Obtained bright yellow solid powder compound 4 (1.1 g, 92%).

The synthetic route of 25245-34-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Chinese Academy Of Sciences Shanghai Organic Chemistry Institute; Zhao Xin; Yin Zhijian; Zhan Tianguang; (17 pag.)CN107353242; (2017); A;,
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Synthetic Route of 22483-09-6, 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 22483-09-6 as follows.

(3,4,5-Trimethoxybenzylidene)-(2,2-dimethoxyethyl)amine (11c). Aminoacetaldehyde dimethylacetal (20.0 mL, 19.5 g, 0.185 mol) was dissolved in chloroform (80 mL) and MgSO4 (15 g) was added. Then 3,4,5-trimethoxybenzaldehyde (10c, 10.03 g, 0.05112 mol) was also added and the mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with chloroform (70 mL), washed with water (4*150 mL), brine (150 mL), dried (Na2SO4), and concentrated to provide the pure imine as a colorless oil (14.47 g, 100%). 1H NMR (300 MHz CDCl3) 8.10 (s, 1H), 6.91 (s, 2H), 4.58 (t, J=5.4 Hz, 1H), 3.81 (s, 6H), 3.79 (s, 3H), 3.69 (s, J, =5.4 Hz, J2=1.2 Hz, 2H), 3.33 (s, 6H).

According to the analysis of related databases, 22483-09-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Cushman, Mark S.; Ioanoviciu, Alexandra S.; Pommier, Yves G.; US2008/242692; (2008); A1;,
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Synthetic Route of 2734-70-5, These common heterocyclic compound, 2734-70-5, name is 2,6-Dimethoxyaniline, 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: To a 0.5 M solution of the acid 9/10 in dichloromethane under nitrogen atmosphere, was added oxalyl chloride (2 eq.) and a few drops of DMF at room temperature. After effervescence subsided, the mixture was heated to reflux at 45 ¡ãC for 2 h. It was then cooled to room temperature, concentrated in vacuo, co-evaporated three times with toluene and then re-dissolved in dichloromethane. The aniline (2 eq.) was then added at 0 ¡ãC, followed by DIPEA (3 eq.) and the mixture stirred overnight at room temperature. The reaction was quenched by addition of NaHCO3 and the aqueous layer was extracted three times with dichloromethane. The combined organic layer was washed once with brine, dried over Na2SO4 and concentrated in vacuo. Purification by silica gel chromatography using a toluene/acetone or dichloromethane/methanol solvent system gave access to the pure protected amides (30percent?75percent yields).

The synthetic route of 2734-70-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Chofor, Rene; Risseeuw, Martijn D.P.; Pouyez, Jenny; Johny, Chinchu; Wouters, Johan; Dowd, Cynthia S.; Couch, Robin D.; Van Calenbergh, Serge; Molecules; vol. 19; 2; (2014); p. 2571 – 2587;,
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These common heterocyclic compound, 202865-59-6, name is 2-Bromo-4,6-difluoroanisole, 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. Safety of 2-Bromo-4,6-difluoroanisole

Palladium (II) acetate (0.040 g, 0.18 mmol) and xantphos (0.104 g, 0.179 mmol) were stirred in toluene (1 mL) at room temperature for 2 min. 1- Bromo-3,5-difluoro-2-methoxybenzene (4.00 g, 17.9 mmol), (diphenylmethylene)hydrazine (3.52 g, 17.9 mmol) and sodium tert-butoxide (2.41 g, 25.1 mmol) were added followed by the addition of toluene (4 mL). The mixture was degassed twice and was stirred for 6 h at 100 C under argon. After cooling, EtOAc and H20 were added. The organic layer was separated. The aqueous phase was extracted one more time with EtOAc. The combined EtOAc layers were washed with I0, then brine, dried over MgSO^ filtered, and concentrated. The crude was dissolved in a small amount of CH2CI2 and added to a silica gel column and was eluted with hexanes/EtOAc to give Intermediate 12A (6.0 g, 15 mmol, 84% yield). lH NMR (400 MHz, CDC13) delta ppm 3.63 (br. s, 3 H), 6.14 – 6.38 (m, 1 H), 7.08 – 7.20 (m, 5 H), 7.45 – 7.68 (m, 5 H), 7.97 (s, 1 H). 9F NMR (376.5 MHz, Acetone-d6) delta ppm -115.46, -129.88.

The synthetic route of 2-Bromo-4,6-difluoroanisole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; THIBEAULT, Carl; CLARK, Charles, G.; DELUCCA, Indawati; HU, Carol, Hui; JEON, Yoon; LAM, Patrick, Y., S.; QIAO, Jennifer, X.; YANG, Wu; WANG, Yufeng; WANG, Tammy, C.; WO2014/22349; (2014); A1;,
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Related Products of 38197-43-2, 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 38197-43-2 as follows.

To a solution of 2-bromo-1-methoxy-3-methylbenzene (Combi-Blocks CAS No.38197-43-2) (1.024 g, 5.09 mmol) in tetrahydrofuran (25.5 mL) was added bis(dibenzylideneacetone)palladium (0.059 g, 0.102 mmol) and Q-Phos (1,2,3,4,5-Pentaphenyl-1′-(di-tert-butylphosphino)ferrocene) (pentaphenyl(di-tert-butylphosphino)ferrocene, 0.072 g, 0.102 mmol). Nitrogen was bubbled through the solution for about 3 minutes, then a 0.4 M in tetrahydrofuran solution of (1-(methoxycarbonyl)cyclopropyl)zinc(II) bromide (25.5 mL, 10.19 mmol) was added dropwise over 5 minutes and the internal temperature rose from 23.5 C. to 24.8 C. The reaction was stirred for 15 hours at ambient temperature, at which point it was quenched with saturated aqueous ammonium chloride (30 mL), diluted with methyl tert-butyl ether (130 mL), and the layers were separated. The organic layer was filtered through a pad of silica gel. The filtrate was concentrated in vacuo to give a crude residue that was purified via flash chromatography, eluting on a 40 g silica gel cartridge with 1-40% ethyl acetate/heptanes over 40 minutes to provide the title compound. 1H NMR (400 MHz, CDCl3) delta ppm 7.15 (t, J=7.9 Hz, 1H), 6.76-6.80 (m, 1H), 6.73 (d, J=8.2 Hz, 1H), 3.80 (s, 3H), 3.60 (s, 3H), 2.32 (s, 3H), 1.71-1.75 (m, 2H), 1.54 (s, 2H)+ MS (ESI+) m/z 221 (M+H)+, 243 (M+Na)+.

According to the analysis of related databases, 38197-43-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Couty, Sylvain; Desroy, Nicolas; Gfesser, Gregory A.; Housseman, Christopher Gaetan; Kym, Philip R.; Liu, Bo; Mai, Thi Thu Trang; Malagu, Karine Fabienne; Merayo Merayo, Nuria; Picolet, Olivier Laurent; Pizzonero, Mathieu Rafael; Searle, Xenia B.; Van der Plas, Steven Emiel; Wang, Xueqing; Yeung, Ming C.; (189 pag.)US2019/77784; (2019); A1;,
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These common heterocyclic compound, 321-28-8, name is 1-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. Recommanded Product: 1-Fluoro-2-methoxybenzene

Step 1. Preparation of 1-(3-fluoro-4-methoxyphenyl)-2-phenyl-ethan-1-one. Aluminum chloride (42.17 g, 316 mmol) and dichloromethane (350 mL) were cooled to 2 C. and phenylacetylchloride (40.50 g, 262 mmol) in dichloromethane (30 mL) was added. 2-Fluoroanisole (32.77 g, 260 mmol) in dichloromethane (30 mL) was added. The cooling bath was removed, and the mixture was stirred for 1 hour. The reaction mixture was poured into concentrated HCl (150 mL), filtered through diatomaceous earth, washed with saturated aqueous NaHCO3, dried over MgSO4, and concentrated. A white solid was obtained by crystallization from dichloromethane/hexane (29.2 g, 46%): mp 105-106 C.

The synthetic route of 1-Fluoro-2-methoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; G. D. Searle & Co.; US5859257; (1999); A;,
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These common heterocyclic compound, 349-65-5, name is 2-Methoxy-5-(trifluoromethyl)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. HPLC of Formula: C8H8F3NO

2-Methoxy-5 (trifluoromethyl) aniline (commercially available) (109.7 mg, 0.551 mmol) was dissolved in 14 mL dichloromethane. Saturated aqueous [NAHCO3] solution (14 mL) was added and the mixture was cooled to [0 C.] While stirring, the mixture was treated with phosgene by addition to the organic layer via syringe in one portion (0.95 mL, 1.92 mmol). The mixture was then stirred vigorously for 0.5 h, then the layers were separated. The aqueous layer was extracted once with dichloromethane and the combined organics were dried [(MGS04),] filtered and the dichloromethane was removed in vacuo. The isocyanate residue was added to the aminonaphthyl pyrimidine ether (186 mg, 0.551 mmol) in 2 mL anhydrous THF. The reaction mixture was left stirring at room temperature overnight and then concentrated in vacuo and triturated with ether to provide 250 mg of a pink solid. The product was purified by column chromatography on silica gel, eluting with 1: 9: 90 [NH40H] : MeOH: [CH2CL2] to provide 110 mg of the title compound as a tan foam.

The synthetic route of 2-Methoxy-5-(trifluoromethyl)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.; WO2004/14870; (2004); A1;,
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Reference of 1535-73-5, A common heterocyclic compound, 1535-73-5, name is 3-Trifluoromethoxyaniline, molecular formula is C7H6F3NO, 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.

To a mixture of compound 3B-1 (2.00 g, 8.98 mmol, 1.0 eq) and compound 3D-1 (1.91 g, 10.8 mmol, 1.2 eq) in isopropanol (20 mL) was added TFA (1.02 g, 8.98 mmol, 1.0 eq) in one portion at 20 ¡ãC under nitrogen. The mixture was stirred at 90 ¡ãC for 18 hours. LC-MS (ET15060-21-P1A1) showed the reaction was completed. The resulting suspension was cooled, and the product was filtered off, washing with a small volume of dichloromethane (10 mL) to give compound 3D-2 (3.00 g, 8.26 mmol, 91.9 percent yield) as yellow solid which was used for next step directly. ln NMR: ET15060-21-P1A1 400 MHz DMSO-d6 9.68 (s, 1H), 8.71 (d, J = 8.8 Hz, 1H), 8.15 (d, J = 6.0 Hz, 1H), 8.03 (s, 1H), 7.91 (dd, J = 8.4, 1.2 Hz, 1H), 7.71 (d, J = 8.4, Hz, 1H), 7.45 (t, J = 8.4 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 6.0 Hz, 1H), 2.48 (s, 3H).

The synthetic route of 1535-73-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LUTRIS PHARMA LTD.; SHELACH, Noa; (76 pag.)WO2019/26065; (2019); A2;,
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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. 366-99-4, name is 3-Fluoro-4-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 3-Fluoro-4-methoxyaniline

Step 2. To a solution of l-(6-chloropyrazin-2-yl)-2-methyl-lH-benzo[d]imidazole (96 mg, 0.36 mmol) and 3-fluoro-4-methoxyaniline (71 mg, 0.5 mmol) in THF (1 mL) at room temperature was added KOt-Bu (1M in THF, 1 mL, 1 mmol). The mixture was reacted for 5 minutes, then the reaction was quenched with AcOH and the product partitioned between ethyl acetate and aqueous ammonium chloride. The organic layer was dried, concentrated and purified by chromatography on silica gel (gradient from ethyl acetate:hexane 1:2 to ethyl acetate: methanol 5: 1). The fractions were concentrated and the residue was washed with an ethyl acetate: ether mixture, then filtered and dried to provide the title compound as a yellow/brown solid (39 mg, 25 percent). ]H NMR (DMSO-i delta 9.93 (s, 1H), 8.31 (s, 1H), 8.25 (s, 1H), 7.61 – 7.68 (m, 2H), 7.51 – 7.55 (m, 1H), 7.32 – 7.36 (m, 1H), 7.26 – 7.26 (m, 1H), 7.23 – 7.30 (m, 2H), 7.14 (t, J = 9.1 Hz, 1H), 3.79 (s, 3H), 2.63 (s, 3H); MS m/z 350 (ESI) [M+H]+.

According to the analysis of related databases, 366-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PTC THERAPEUTICS, INC.; BAIAZITOV, Ramil; CHOI, Soongyu; DU, Wu; HWANG, Seongwoo; LEE, Chang-Sun; LIU, Ronggang; MOON, Young-Choon; PAGET, Steven, D.; REN, Hongyu; SYDORENKO, Nadiya; WILDE, Richard, Gerald; WO2015/76800; (2015); A1;,
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Reference of 538-86-3, 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. 538-86-3 name is (Methoxymethyl)benzene, 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.

General procedure: A mixture of nitriles (5 mmol), methyl ethers (6 mmol) and Fe(ClO4)3¡¤H2O (5percentmol) was placed in a round bottom flask. Then the reaction mixture was heated at 100 ¡ãC for the given time. After completion of the reaction monitored by thin layer chromatography (TLC), 10 ml water was added into reaction system and extracted with ethyl acetate (3 ¡Á 20 ml). The organic layers were collected, combined, washed with water (3 ¡Á 20 ml), dried over anhydrous Na2SO4, and concentrated under vacuum. The pure products (1a?1k and 2a?2p) were obtained by directly passing through a silica gel (200?300 mesh) column using petroleum ether/ethyl acetate (10:1?5:1).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (Methoxymethyl)benzene, and friends who are interested can also refer to it.

Reference:
Article; Yin, Guibo; Yan, Bin; Chen, Junqing; Ji, Min; Journal of the Iranian Chemical Society; vol. 16; 6; (2019); p. 1355 – 1363;,
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