Category: ethers-buliding-blocks

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. 22236-10-8, name is 4-(Difluoromethoxy)aniline, A new synthetic method of this compound is introduced below., 22236-10-8

General procedure: Ethyl 4-bromo-1H-indole-2-carboxylate (1 eq), Pd2(dba)3 (0.1 eq), X-phos(0.2 eq), Cs2CO3 (3 eq) and aryl amine (3 eq) was added to a microwave tube,dissolved in 1,4-dioxane, and filled with argon gas. The microwave reaction wascarried out at 100 C for 0.5-1.5 h, and the starting material disappeared. The mixturewas cooled to room temperature and concentrated. Ethyl acetate was added todissolve the residue, and the mixture was washed with saturated brine and water, driedover anhydrous Na2SO4, and concentrated in vacuo. The crude product was purifiedby column chromatography to afford the target compound. Compounds 8m-8o, 8s,8a-3 ~ 8a-5, 8a-13, 8a-15 ~ 8a-17, 8o-1 ~ 8o-24 were prepared with method 3.

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:
Article; Cui, Guonan; Lai, Fangfang; Wang, Xiaoyu; Chen, Xiaoguang; Xu, Bailing; European Journal of Medicinal Chemistry; vol. 188; (2020);,
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The chemical industry reduces the impact on the environment during synthesis 588-96-5, name is p-Bromophenetole, I believe this compound will play a more active role in future production and life. 588-96-5

General procedure: In air, aryl halide (0.2 mmol), arylboronic acid (0.22 mmol),K2CO3 (0.3 mmol), 5 ml of distilled water, and 2 mg of catalystwere combined in a 10 ml round bottom flask. The reactionmixture was magnetically stirred and the temperature wasmaintained at 75 C in an oil bath. Reaction progress was monitoredby TLC. After reaction was completed, the reaction mixturewas cooled to room temperature and filtrated. The filtratedsolid was washed with water (35 ml) and dissolved withethyl acetate. The catalyst was separated by filtration, washedwith water, and dried in vacuum. The combined organic phasewas dried with anhydrous MgSO4, and the solvent was removedunder reduced pressure to give the product.

The chemical industry reduces the impact on the environment during synthesis 588-96-5. I believe this compound will play a more active role in future production and life.

Reference:
Article; Ma, Hengchang; Bao, Zhikang; Han, Guobin; Yang, Ningning; Xu, Yufei; Yang, Zengming; Cao, Wei; Ma, Yuan; Cuihua Xuebao/Chinese Journal of Catalysis; vol. 34; 3; (2013); p. 578 – 584;,
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103291-07-2, 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. 103291-07-2, name is 4-Bromo-1-fluoro-2-methoxybenzene, A new synthetic method of this compound is introduced below.

To a solution 5-bromo-2-fluoroanisole (109 g, 0.54 mol), ZnF2 (2.52 g, 24.39 mmol), Pd(dba)2 (3.08 g, 5.35 mmol), and P^Bu3 (5.2 mL of a 50% solution in toluene, 11 mmol) in DMF (1 L) was added trimethylsilyl methyl ketene acetal (121 g, 0.7 mol). The reaction mixture was stirred at 80-90 0C for 5 h under nitrogen atmosphere and then was allowed to cool to room temperature and diluted with EtOAc. The reaction mixture was filtered through Celite. The filtrate was washed with H2O (2 L) and the aqueous layer was extracted with EtOAc (2.5 L). The combined extracts were washed with brine (2 L x 2), dried over MgSO4, and concentrated at reduced pressure to give methyl 2-(4-fluoro-3- methoxyphenyl)-2-methylpropanoate (151 g), which was used for the next step without further purification. 1U NMR (400MHz, CDCl3): delta 7.04-6.98 (m, IH), 6.95-6.92 (dd, IH), 6.88-6.85 (m, IH), 3.89 (s, 3H), 3.67 (s, 3H), 1.57 (s, 6H).

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; EXELIXIS, INC.; BOLLU, Venkataiah; BOREN, Brant, Clayton; DALGARD, Jackline, Eve; FLATT, Brenton, T.; HAQ, Nadia; HUDSON, Sarah; MOHAN, Raju; MORRISSEY, Michael; PRATT, Benjamin; WANG, Tie-lin; WO2010/93845; (2010); A1;,
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14869-41-1, 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. 14869-41-1 name is 2-(2-Chloroethoxy)acetic acid, 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.

90 ml toluene, lO.OOg 2-(2-chloroethoxy)acetic acid (X) oily extract obtained from one of the previous examples, 8.3 Ig 4-nitro-aniine and l .84g phenyl -boronic acid are measured into a 125 ml volume sulfonating flask equipped with a Dean-Stark attachment, a condenser and thermometer. The mixture is heated to the reflux temperature (1 10- 1 11 C), the reaction is checked by a TLC method. After the end of the reaction the mixture is cooled back, 1.00 ml ethylene-glycol is added. Then the mixture is heated again to the temperature of reflux, then it is refluxed for another half an hour. Then the mixture is cooled to a temperature of 0-5C. The suspension is filtered and washed with toluene. The filtrate is dried to a constant mass. The mass of the obtained pastel yellow powder: 12.98g, yield: 83%

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-(2-Chloroethoxy)acetic acid, and friends who are interested can also refer to it.

Reference:
Patent; RICHTER GEDEON NYRT.; SZABO, Tamas; NEU, Jozsef; GARADNAY, Sandor; (17 pag.)WO2019/138362; (2019); A1;,
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3616-56-6, 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. 3616-56-6, name is 2,2-Diethoxy-N,N-dimethylethanamine, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: Dimethylaminoacetaldehyde diethyl acetal (5 mmol) was added to a solution of 7 (0.5 mmol) in AcOH (5mL) at room temperature, and the mixture was heated at 100 ¡ãC. After 1 h, the mixture was gradually cooled to room temperature. The mixture was diluted with AcOEt (100 mL), washed with saturated NaHCO3 solution and brine, and dried over MgSO4. The solvent was removed, and the residue was separated by silica gel column chromatography with hexane/AcOEt (5:1) to give 3, 4 and 8.

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:
Article; Abe, Takumi; Ishikura, Minoru; Heterocycles; vol. 90; 1; (2015); p. 673 – 680;,
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1535-75-7, Adding some certain compound to certain chemical reactions, such as: 1535-75-7, name is 2-(Trifluoromethoxy)aniline, 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 1535-75-7.

General procedure: The general procedure for the preparation of (R)-2-amino-3,3,3-trifluoro-2-methyl-N-phenylpropanamide derivatives was as follows. Reactions were carried out according to the literature procedure reported by Zhichkin et al2 with slight modifications. The Vilsmeier reagent was prepared by adding oxalyl chloride (2.52 g, 19.8 mmol) dropwise to a solution of anhyd. DMF (1.50 g, 20.5 mmol) in CH2Cl2 (20 mL) at 0-5 ?C (CAUTION: Foaming.) and stirring at rt for 30 min. Compound 5 (1.93 g, 10.0 mmol) was added at 0 ?C to Vilsmeier reagent (20.0 mmol) in CH2Cl2 (20 mL) prepared as described above, and the mixture was stirred at rt for 2 h. At 0 ?C, a solution of substituted aniline (10.0 mmol) in CH2Cl2 (10 mL) was added, followed by DIPEA (5.30 g, 41.0 mmol), and the mixture was stirred for 1 h at rt. It was then concentrated to dryness, and the residue was heated at reflux in ethanol (25 mL) with ethylenediamine (2.70 g, 45.0 mmol) for 3 h. The resulting mixture was evaporated to dryness, stirred with water (50 mL) and partitioned between CH2Cl2 and water. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by column chromatography (petroleum ether/ethyl acetate) to afford the desired compounds.

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 1535-75-7.

Reference:
Article; Li, Tian-Wen; Shang, Pei-Hua; Cheng, Chang-Mei; Zhao, Yu-Fen; Tetrahedron Letters; vol. 54; 2; (2013); p. 134 – 137;,
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A common heterocyclic compound, 22236-10-8, name is 4-(Difluoromethoxy)aniline, molecular formula is C7H7F2NO, 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. 22236-10-8.

Following General Procedure A, a solution of 4-difluoromethoxyaniline (0.50 g, 3.1 mmol) and (R)-3-(4-oxo-piperidin-1-yl)-butyronitrile (0.44 g, 2.6 mmol) in CH2Cl2 (10 mL), was treated with glacial AcOH (3 drops) and NaBH(OAc)3 (0.83 g, 3.9 mmol), stirring for 16 h at room temperature. Saturated aqueous NaHCO3 solution (15 mL) and 1N NaOH (2 mL) was added and the phases were separated and the aqueous extracted with CH2Cl2 (2¡Á15 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was then purified by flash column chromatography on silica gel (1:1 EtOAc/CH2Cl2) to afford (R)-3-[4-(4-difluoromethoxy-phenylamino)-piperidin-1-yl]-butyronitrile as a white solid (0.61 g, 76%). 1H NMR (CDCl3) delta 1.20 (d, 3H, J=6.6 Hz), 1.43 (m, 2H), 2.06 (br d, 2H), 2.36 (m, 3H), 2.52 (m, 1H), 2.82 (m, 2H), 3.07 (sex, 1H, J=7.2 Hz), 3.24 (m, 1H), 6.36 (t, 1H, J=75 Hz), 6.54 (d, 2H, J=9.0 Hz), 6.95 (d, 2H, J=9.0 Hz).

The synthetic route of 4-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AnorMED Inc.; US2005/277668; (2005); A1;,
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1535-73-5,Some common heterocyclic compound, 1535-73-5, name is 3-Trifluoromethoxyaniline, molecular formula is C7H6F3NO, 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 an ice-salt bathcooled solution of 3 (7.65 g, 50.0 mmol), hydrochloric acid (150 mL), a solution of sodium nitrite (3.6 g, 50.0mmol, 50 mL/H2O) was added dropwise, the mixture was left to stir for 30 minutes, followed by addition of 3-trifluromethoxyalinine dissolved in 50 mL alcohol, and neutralized with sodium acetate, the mixture was stirredfor 2 hours while the reaction temperature was kept between -5 to 0 ¡ãC, before pouring into 2000 mL cold waterand stirring, the solid was filtered and washed with water until the filtrate was colorless, the crude productobtained was recrystallized with ethyl acetate to give 8.55 g 4 as orange-yellow solid (50percent).

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

Reference:
Article; Fan, Yin-Bo; Li, Kun; Huang, Min; Cao, Yu; Li, Ying; Jin, Shu-Yu; Liu, Wen-Bing; Wen, Jia-Chen; Liu, Dan; Zhao, Lin-Xiang; Bioorganic and Medicinal Chemistry Letters; vol. 26; 4; (2016); p. 1224 – 1228;,
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402-07-3,Some common heterocyclic compound, 402-07-3, name is 4-Bromo-3-methoxybenzotrifluoride, molecular formula is C8H6BrF3O, 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.

Synthesis of (2-(Hydroxy(2-methoxy-4-(trifluoromethyl)phenyl)methyl)- 1 ‘-tosyl-l – 1 ,3 ‘- bipyrrol-2’-yl)(2-methoxy-4-(trifluoromethyl)phenyl)methanone (37). To a solution of l-bromo-2-methoxy-4-(trifiuoromethyl)benzene (720 mg, 2.88 mmol) in dry THF (5 mL) at -78 C under N2 was slowly added n-BuLi (1.15 mL, 2.5 M in n-pentane, 2.88 mmol). After being stirred for 30 min, a solution of 36 (550 mg, 1.06 mmol) in dry THF (1 mL) was added slowly via a syringe. The mixture was stirred for about 2 h and quenched by addition of a saturated aqueous NH4C1 (15 mL) solution and extracted with EtO Ac (10 mL x 3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue was purified by flash column chromatography (15% EtO Ac/petroleum) to give 37 (400 mg, 54% yield) as a light yellow solid. 1H NMR (400 MHz, CDCI3) delta 2.44 (s, 3H), 3.59 (br s, 3H), 3.84 (s, 3H), 5.77 (br s, 1H), 6.17-6.32 (m, 3H), 6.49 (br s, 1H), 6.70 (br s, 1H), 6.83 (d, J= 7.6 Hz, 1H), 7.13 (br s, 1H), 7.21 (br s, 1H), 7.35-7.37 (m, 4H), 7.42 (d, J= 2.8 Hz, 1H), 7.92 (d, J= 8.0 Hz, 2H) ppm; 13C NMR (CDC13, 100 MHz) delta 21.67, 55.75, 55.88, 67.96, 105.60, 105.64, 108.13, 108.03, 111.28, 116.78, 116.78, 116.78, 120.85, 120.85, 124.97, 126.20, 127.10, 127.30, 127.63, 127.63, 129.14, 129.14, 129.98, 129.98, 132.50, 132.56, 133.21, 133.45, 135.92, 145.38, 155.48, 157.01, 180.50 ppm; IR (KBr) 3444, 3137, 2923, 1668, 1562, 1447, 1361, 1180, 1014, 752, 668 cm”1.

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-methoxybenzotrifluoride, its application will become more common.

Reference:
Patent; CHONGQING ZEIN PHARMACEUTICAL CO., LTD.; H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.; QIN, Yong; CHENG, Chunwei; SONG, Hao; LI, Rongshi; LIU, Yan; WO2014/116634; (2014); 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. 22236-08-4, name is 3-(Difluoromethoxy)aniline, This compound has unique chemical properties. The synthetic route is as follows., 22236-08-4

General procedure: A two neck round bottom flask under argon equipped with acondenser was charged with aldehyde 4 (1.0 equiv.) and 4-chloroaniline 3l (1.1 equiv.) in 2-pentanol [0.3 M] and stirred atreflux for 2 h. The tetronic acid 5 (1.1 equiv.) in 2-pentanol (minimumamount) was then added at reflux. After another 10 min atreflux, the third component aniline 3 (1.0 equiv.) was added neat.The reaction mixture was refluxed for an additional 30 min. Allvolatiles were evaporated under vacuum and the crude product purified by recrystallization in ethanol or by flash chromatographyon silica gel

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:
Article; Jeedimalla, Nagalakshmi; Flint, Madison; Smith, Lyndsay; Haces, Alberto; Minond, Dmitriy; Roche, Stephane P.; European Journal of Medicinal Chemistry; vol. 106; (2015); p. 167 – 179;,
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