Author: Jessica.F

Synthetic Route of 41789-95-1, These common heterocyclic compound, 41789-95-1, name is 1-(3-Methoxyphenyl)-N-methylmethanamine, 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 8; 3-amino-4-(2,4-dichlorophenyl)-N-(3-methoxybenzyl)-N-methylpyrrolidine-1-carboxamide A solution of 1-benzyl-3-(2,4-dichlorophenyl)-4-nitropyrrolidine (1.5 g, 4.3 mmol) in dry CH2Cl2 (5 mL) was cooled to 0 C. and triphosgene (500 mg, 1.7 mmol) in CH2Cl2 was added over the course of 30 minutes. The reaction was quenched with H2O and extracted with CH2Cl2. The organics were then washed with saturated aqueous NaHCO3, dried, filtered and concentrated under reduced pressure. The crude material was divided into 10 portions (0.43 mmol each), and (3-methoxy-benzyl)methyl-amine (45 mg, 0.30 mmol), Et3N (30 mg, 0.30 mmol) and CH2Cl2 (1 mL) were added to a single portion. The solution was stirred for 4 hours and concentrated under reduced pressure. The unpurified material was taken up in 1:1 MeOH/AcOH (2 ml) and zinc dust (200 mg, 3 mmol) was added. After stirring 4 hours, the solution was carefully quenched with saturated aqueous NaHCO3 and extracted with several portions of EtOAc. The organics were combined, concentrated under reduced pressure and purified employing reverse phase chromatography (samples were purified by preparative HPLC on a Waters Symmetry C8 column (25 mm¡Á100 mm, 7 um particle size) using a gradient of 10% to 100% acetonitrile: 0.1% aqueous TFA over 8 minutes (10 minutes run time) at a flow rate of 40 mL/minutes) to provide the title compound. 1H NMR (300 MHz, d6-DMSO) delta ppm 7.60-7.61 (m, 1H), 7.39-7.43 (m, 2H), 7.24-7.27 (m, 1H), 6.82-6.85 (m, 3H), 4.30-4.34 (m, 2H), 3.73-3.84 (m, 4H), 3.47-3.54 (m, 2H), 3.27-3.34 (m, 2H), 3.14-3.18 (m, 1H), 2.67-2.73 (s, 3H). MS (ESI+) m/z 408 (M+H)+

The synthetic route of 41789-95-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Backes, Bradley J.; Hamilton, Gregory L.; Kopecka, Hana A.; Lai, Chunqiu; Longenecker, Kenton L.; Madar, David J.; Pei, Zhonghua; Stewart, Kent D.; Von Geldern, Thomas W.; US2006/264433; (2006); A1;,
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Reference of 103291-07-2, A common heterocyclic compound, 103291-07-2, name is 4-Bromo-1-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.

Add sodium hydride (2.77 g, 60% w/w, 69.2 mmol) to a solution of 3-hydroxy- azetidine-1-carboxylic acid tert-butyl ester (10.9 g, 62.9 mmol) in dimethyl sulfoxide (100 mL). Stir the mixture for 30 min and then add 3-bromo-6-fluoroanisole (15.5 g, 75.5 mmol). Heat the mixture to 65 0C overnight. Cool the mixture to room temperature and then dilute the solution with saturated ammonium chloride and brine and extract with ethyl acetate. Wash the organics five times with brine, then dry over sodium sulfate and filter. Concentrate and purify via silica gel chromatography using a 0-45% gradient of ethyl acetate/hexane to give 10.4 g (46%) of the title compound as a clear oil.

The synthetic route of 103291-07-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2008/76562; (2008); A1;,
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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;,
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Reference of 19056-40-7, 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. 19056-40-7, name is 4-Bromo-3-methoxyaniline, This compound has unique chemical properties. The synthetic route is as follows.

b 5-Amino-2-bromo-phenol A suspension of 4-bromo-3-methoxy-phenylamine (37.6 g, 0.186 mol) and tetrabutylammonium iodide (96 g, 0.260 mol) in dichloromethane (1.2 L) was cooled down to -78 C. A 1M solution of boron trichloride in dichloromethane (520 mL, 0.521 mol) was added dropwise, within 20 min. The cooling bath was removed. After 3 hours, the reaction mixture was poured onto ice water (4.5 kg). The organic layer was extracted with water. The combined aqueous layers were washed with dichloromethane. The pH was adjusted to 9 using sodium hydrogencarbonate. Sodium chloride was added until saturation. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and the solvents were evaporated. The solid was washed with dichloromethane and dried under vacuum. 35.2 g of the title compound were obtained. Brown solid, ISP-MS: m/e=189.1 ([M+H]+).

The chemical industry reduces the impact on the environment during synthesis 4-Bromo-3-methoxyaniline. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Klug, Michael G.; Mattei, Patrizio; Mueller, Werner; Neidhart, Werner; Nettekoven, Matthias Heinrich; Pflieger, Philippe; Plancher, Jean-Marc; US2003/158179; (2003); 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 1535-75-7 as follows. Quality Control of 2-(Trifluoromethoxy)aniline

General procedure: Acetamides (1a-1x, 1ab, 1ac and 1ba-1bc). To a solution of 2-phenylacetic acid (7.0mmol), 2-(trifluoromethoxy)aniline (7.7mmol) in anhydrous CH2Cl2 (25mL) were added EDCI (1.745g, 9.1mmol) and DMAP (256.6mg, 2.1mmol). The reaction mixture was stirred at room temperature overnight, diluted with HCl (1M) aqueous solution, and extracted with CH2Cl2 (3¡Á25mL). The combined organic phase was washed with saturated NaHCO3 aqueous solution and brine, dried over anhydrous Na2SO4, and concentrated under vacuum. Purification by flash chromatography (Silica gel, petroleum ether: ethyl acetate=50: 1 as eluent) gave the corresponding 2-phenyl-N-[2-(trifluoromethoxy)phenyl]acetamide compound.

According to the analysis of related databases, 1535-75-7, the application of this compound in the production field has become more and more popular.

Reference:
Article; Zhao, Xiao-Jing; Zhao, Jie; Sun, Xin; Liu, Ji-Kai; Wu, Bin; Tetrahedron; vol. 73; 25; (2017); p. 3463 – 3477;,
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707-07-3, name is (Trimethoxymethyl)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. Safety of (Trimethoxymethyl)benzene

Raney Ni (1.5 g) is added to a mixture of commercially available nitrogen- containing 4-methyl-3-nitropyridin-2-amine x220 (4.0 g, 26.1 mmol) in methanol (150 ml), and the obtained reaction mixture is hydrogenated in the Parr apparatus at the hydrogen pressure 3 atm until the total conversion of compound x220 is attained for approximately 1.5-2 h. The catalyst is separated by filtration, the filtrate is washed with methanol, and the alcohol solution is evaporated to dryness. The residue is dissolved in sulfolane (10 ml), then PhC(OMe)3 (5.7 g, 1.2 eq, 31.3 mmol) and PTSA (0.3 g) are added, and an air reflux condenser is mounted. The apparatus is argon-blown, and the obtained reaction mixture is heated to 165 0C under vigorous stirring for 10 h. Water (100 ml), saturated aqueous NaHCC>3 (5 ml), and hexane (50 ml) are added to the reaction mixture. The obtained suspension is stirred for 5 min, and the residue is separated by filtration. The residue is washed with water (50 ml) and hexane (100 ml), and vacuum-dried over P2O5 to a constant weight at 45 0C to give 7-methyl-2-phenyl-3H-imidazo[4,5-b]pyridine x221 (2.2 g).Yield: 40 %. LC-MS (MH+): 210.

The synthetic route of 707-07-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; UCB S.A.; WO2006/128692; (2006); A2;,
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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. 1484-26-0, name is 3-Benzyloxyaniline, A new synthetic method of this compound is introduced below., Quality Control of 3-Benzyloxyaniline

Compound 19A (commercially available) (10.0 g, 50.25 mmol) was dissolved in water at room temperature and to resulting suspension K2CO3 ( 3.8 g, 27,64 mmol) was added. 3- Chloro propionylchloride (7.0 g. 55.28 mmol) was added dropwise for 30 minutes and stirred for 2 hours at room temperature The precipitate was filtered and washed with water. 1 N HCl, dried at 50 0C under vacuum overnight to provide 7.2 g of the product 19B.

The synthetic route of 1484-26-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SCHERING CORPORATION; WO2009/152200; (2009); A1;,
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Application of 1758-46-9,Some common heterocyclic compound, 1758-46-9, name is 2-Phenoxyethylamine, molecular formula is C8H11NO, 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 solution of 2-phenoxy-ethylamine (5 eq.) or 2-(2-methoxyphenoxy-)ethylamine (5 eq.) in 2-methoxyethanol(25 mL per mmol of amine) the appropriate aliphatic chloride33-39 (1 eq.) and KI (cat.) was added. The mixturewas refluxed for18-48 h and concentrated. The residue was suspended in CHCl3and washed with 1M NaOH, brine, dried over anhydrous Na2SO4and concentrated. The crude was purified by flash chromatographyto give the titled compound.

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

Reference:
Article; Franchini, Silvia; Sorbi, Claudia; Linciano, Pasquale; Carnevale, Gianluca; Tait, Annalisa; Ronsisvalle, Simone; Buccioni, Michela; Del Bello, Fabio; Cilia, Antonio; Pirona, Lorenza; Denora, Nunzio; Iacobazzi, Rosa Maria; Brasili, Livio; European Journal of Medicinal Chemistry; vol. 176; (2019); p. 310 – 325;,
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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. 38336-04-8, name is 2-(Benzyloxy)-1-ethanamine, A new synthetic method of this compound is introduced below., Product Details of 38336-04-8

Benzethylethanolamine trimethylene carbonate: 2.7 g of benzyl alcoholamine modified 1,3-propanediol, 2.4 g of ethyl chloroformate and 30 ml of anhydrous tetrahydrofuran were placed in a 50 ml round bottom flask and stirred in an ice bath , 1.2 g of triethylamine dropwise, about 10 minutes drop finished. Remove the ice bath and react at room temperature for 2 hours. After filtration, the filtrate was concentrated and excess unreacted ether was added to precipitate white crystals and recrystallized three times with a mixed solvent of tetrahydrofuran and anhydrous ether in a volume ratio of 1: 3 to give white crystals in a yield of 64%. The infrared (FT-IR), nuclear magnetic resonance spectrum (1H NMR and 13C NMR) and elemental analysis (EA) data were the same as in Example 1

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; China University Of Geoscienceswuhan; ZHANG, Xiaojin; DAI, Yu; (6 pag.)CN106518836; (2017); A;,
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Adding a certain compound to certain chemical reactions, such as: 36865-41-5, name is 1-Bromo-3-methoxypropane, 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 36865-41-5, name: 1-Bromo-3-methoxypropane

To a 1 L single-neck flask were added methyl 4-bromo-2-hydroxybenzoate (44.5 g, 193 mmol) and CH3CN (450 mL). After the solid was dissolved completely by stirring, K2C03 (39.9 g, 289 mmol) and 1-bromo-3-methoxypropane (45.1 g, 289 mmol) were added in turn. The resulting mixture was heated to 80 C and stirred for 12 hours at 80 C. After the reaction was completed, the reaction mixture was cooled to 25 C and filtered. The filter cake was washed with acetonitrile (100 mL). The combined filtrates was concentrated in vacuo, and the residue was diluted with EtOAc (500 mL). The mixture was washed with saturated brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound as orange oil (58 g, 99.3%).MS (ESI, pos.ion) m/z: 303.2 [M¡ÂH] .

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; LIU, Xinchang; REN, Qingyun; HUANG, Jianzhou; XIONG, Zhimin; XIONG, Jinfeng; LI, You; LIU, Yang; ZOU, Zhifu; YAN, Guanghua; GOLDMANN, Siegfried; ZHANG, Yingjun; (2 pag.)WO2018/219356; (2018); A1;,
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