Tag: M.W=100-200

111-95-5, A common heterocyclic compound, 111-95-5, name is Bis(2-methoxyethyl)amine, molecular formula is C6H15NO2, 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 36; N,N-bis(2-methoxyethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-8-amine dihydrobromide; (1) tert-butyl 8-[bis(2-methoxyethyl)amino]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate; A solution of tert-butyl 8-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (200 mg, 0.609 mmol), bis(2-methoxyethyl)amine (0.270 ml, 1.83 mmol), X-phos (17.4 mg, 0.0365 mmol), tris(dibenzylideneacetone)dipalladium(0) (11.0 mg, 0.0120 mmol), sodium tert-butoxide (87.5 mg, 0.912 mmol) and dioxane (4 ml) was stirred under an argon atmosphere for 2 hr at 80C. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the desired product (230 mg, 99.1%) as an oil. 1H-NMR (CDCl3) 5; 1.42 (9H, s), 3.34 (6H, s), 3.52 (8H, s), 3.69-3.76 (2H, m), 4.01-4.04 (2H, m), 4.31-4.38 (2H, m), 6.32-6.39 (2H, m), 6.97-6.99 (1H, m)..

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

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2123644; (2009); 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. 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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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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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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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 14869-41-1 as follows. 14869-41-1

2-Chlorethoxyacetic acid (1.11 g, 8 mmol) is dissolved in dichloromethane (22 mL), and thereto are added thionyl chloride (1.17 mL, 16 mmol) and dimethylformamide (30 muL, 0.4 mmol) successively at room temperature. After stirring at room temperature for 2.5 hours, the mixture is concentrated, and the residue is dissolved in dichloromethane (22 mL). To the mixture are added methyl 4-aminobenzoate (661 mg, 4 mmol) and pyridine (674 muL, 8 mmol) under ice-cooling, followed by stirring overnight. The reaction solution is washed with dilute hydrochloric acid, dried, and concentrated. The residue is subjected to silica gel column chromatography to give ethyl 4-(2-chloroethoxyacetylamino)benzoate (540 mg, 23.6percent).

According to the analysis of related databases, 14869-41-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; TANABE SEIYAKU CO., LTD.; EP1640373; (2006); A1;,
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1579-40-4, Name is Di-p-tolyl Ether, 1579-40-4, 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.

Representative Experimental Protocol: 2,7-Dimethyl-9-(4-nitro)phenyl xanthen-9-ol (R = NO2: 3e): Di-p-tolyl ether (1, 5 g, 25.5 mmol), 4-nitro benzoic acid (5.13 g, 30.7 mmol) and ZnCl2 (10 g, 73.4 mmol) are taken into a 100 ml double neck RB flask and charged with POCl3 (7.5 mL) and heated to 95 C for 4 h. The reaction mixture turned into a brown viscous mass that was difficult to stir. The reaction mixture was then cooled to room temperature and crushed ice was added slowly while keeping the low temperature. To the above mixture was added H2O (75 mL) and stirred for 12 h. The above reaction mixture was filtered and the residue was washed with H2O (20 mL) and hexane (20 mL) to afford 4-nitro-DMPx 3e as white powder. The crude product was dissolved in EtOAc and washed with NaHCO3 to remove the excess of 4-nitro benzoic acid. The EtOAc layer was evaporated under reduced pressure to furnish the desired product as fine powder 7.5 g (86%).

Statistics shows that Di-p-tolyl Ether is playing an increasingly important role. we look forward to future research findings about 1579-40-4.

Reference:
Article; Banerjee, Shyamapada; Srishylam; Rajendra Prasad; Migawa, Michael T.; Swayze, Eric E.; Sanghvi, Yogesh S.; Tetrahedron Letters; vol. 53; 35; (2012); p. 4669 – 4672;,
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