Ethers-buliding-blocks

658-89-9, A common heterocyclic compound, 658-89-9, name is 4-(Trifluoromethoxy)benzene-1,2-diamine, molecular formula is C7H7F3N2O, 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.

Step 1. Preparation of 83-1: HATU (3.06 g, 8.05 mmol) was added slowly to a solution of 3,3-difluoro-2-oxopent-4-enoic acid (1 .03 g, 6.86 mmol) in 10 mLof DMF. A mixture of 4-(trifluoromethoxy)benzene-1 ,2-diamine (1 .29 g, 6.71 mmol) and DIPEA (1.4 mL, 8.05 mmol) in 12 mL of DMF was then added. After stirring overnight, reaction mixture was poured into 175 mL of water and extracted with ethyl acetate (4 x 100 mL). Combined organics were washed with 50% brine, dried over anhydrous Na2504, filtered, and concentrated underreduced pressure. Resulting solid was purified via silica gel column chromatography (0-25% ethyl acetate in hexanes)to yield intermediate 83-1, the late eluting product. LCMS-ESI (m/z): [Mi-H] calcd for C12H8F5N202: 307.04; found: 307.29.

The synthetic route of 658-89-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GILEAD SCIENCES, INC.; BJORNSON, Kyla; CANALES, Eda; COTTELL, Jeromy, J.; KARKI, Kapil, Kumar; KATANA, Ashley, Anne; KATO, Darryl; KOBAYASHI, Tetsuya; LINK, John, O.; MARTINEZ, Ruben; PHILLIPS, Barton, W.; PYUN, Hyung-jung; SANGI, Michael; SCHRIER, Adam, James; SIEGEL, Dustin; TAYLOR, James, G.; TRAN, Chinh, Viet; TREJO MARTIN, Teresa, Alejandra; VIVIAN, Randall, W.; YANG, Zheng-Yu; ZABLOCKI, Jeff; ZIPFEL, Sheila; WO2014/8285; (2014); A1;,
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2859-78-1, A common heterocyclic compound, 2859-78-1, name is 4-Bromo-1,2-dimethoxybenzene, molecular formula is C8H9BrO2, 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.

METHOD AThe synthesis of (i?)-l-(3,4-dimethoxyphenyl)-3-methylpiperazine.HCl is a representative example of the general two step method of making secondary amine building blocks of the type (V) using a palladium coupling reaction. (R)-tert-bntyl 4-(3,4-dimethoxyphenyl)-2-methylpiperazine-l-carboxylate Palladium(II) acetate (0.052 g, 0.230 mmol) and (R)-(+)-2,2′-bis(diphenylphosphino)-l,l?- binaphthyl (0.115 g, 0.180 mmol) were added to 4-bromoveratrole (0.662 mL, 4.61 mmol), (R)–N-boc-2 -methyl piperazine (0.923 g, 4.61 mmol) and sodium tert-butoxide (0.664 g, 6.91 mmol) in anhydrous toluene (12 mL) under argon. The resulting solution was stirred at reflux for 16 hours. The reaction mixture was diluted with Et2O and filtered through celite. The resulting mixture was evaporated to dryness to afford crude (R)-tert-butyl 4- (3,4-dimethoxyphenyl)-2-methylpiperazine-l-carboxylate. The crude product was purified by flash silica chromatography, elution gradient 0 to 25% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-tert-butyl 4-(3,4-dimethoxyphenyl)-2- methylpiperazine-1-carboxylate (0.871 g, 56.2 %) as a beige solid. MS (+ve ESI) : Rt = 2.57 min, 337.31 (M+H)+1H NMi? (400.132 MHz, CDC13) delta 1.33 (3H, d), 1.49 (9H, s), 2.67 (IH, m), 2.85 (IH, m), 3.24 (2H, m), 3.37 (IH, d), 3.84 (3H, s), 3.88 (3H, s), 3.94 (IH, m), 4.34 (IH, s), 6.43 (IH, m), 6.54 (IH, d), 6.79 (IH, d)(R)-l-(3,4-dimethoxyphenyl)-3-methylpiperazine.HCl(R)-tert-buty{ 4-(3,4-dimethoxyphenyl)-2-methylpiperazine-l-carboxylate (0.400 g, 1.19 mmol) was added to hydrochloric acid in methanol (methanol reagent 10) (15 mL, 1.19 mmol) and the resulting solution was stirred at room temperature for 16 hours. The resulting mixture was evaporated to dryness and the residue was azeotroped with DCM to afford crude (i?)-l-(3,4-dimethoxyphenyl)-3-methylpiperazine (100 %). MS (+ve ESI) : Rt = 1.22 min, 237.30 (M+H)+

The synthetic route of 2859-78-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2009/1127; (2008); A1;,
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Adding a certain compound to certain chemical reactions, such as: 768-70-7, name is 3-Ethynylanisole, 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 768-70-7, 768-70-7

General procedure: To a mixture of alpha-azidoamide 16aa (34 mg, 0.20 mmol) and phenylacetylene (9a; 24 L,0.20 mmol) in t-BuOH/H2O (2 mL, 1:1) were added 0.5 M CuSO4 (0.020 mL, 0.010 mmol) and 1.0 M sodium ascorbate (0.020 mL, 0.020 mmol). The reaction mixture was stirred at room temperature for 1 day, and then the resulting reaction mixture was filtered. The separated solid was washed with H2O and hexanes, and triturated with hexane/EtOAc (10:1) to give the 1-morpholino-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethanone (2aaa; 52 mg, 96%) as a white solid

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 3-Ethynylanisole, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Lee, Doohyun; Kim, Daehun; Lee, Seungyeon; Kim, Taegeum; Kim, Joobin; Kim, Sohee; Liu, Kwang-Hyeon; Lee, Sangkyu; Bae, Jong-Sup; Song, Kyung-Sik; Cho, Chang-Woo; Son, Youn Kyung; Baek, Dong Jae; Lee, Taeho; Molecules; vol. 20; 11; (2015); p. 19984 – 20013;,
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75148-49-1, 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. 75148-49-1, name is 3-Bromobenzaldehyde Diethyl Acetal, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: One equiv. of protected hydrazine was dissolved/suspended in EtOH containing 10% water (approx. 5 ml per 1 mmol of protected hydrazine), 1.05 eq of benzaldehyde acetal was added, followed by the addition of 0.05 equiv. of TsOH in an ethanolic solution (10 mg of TsOH per 0.5 ml of EtOH). The obtained reaction mixture was refluxed and monitored by TLC (silica gel) until full conversion of the starting material was observed. Ethyl acetate/light petroleum mixtures or pure ethyl acetate were used as TLC eluents. After completion of the reaction the solvent was removed under reduced pressure, approx. 15 ml of toluene was added to the residue and the solvent was again removed under reduced pressure. The obtained crude hydrazone was dissolved in commercial stabilized THF (approx. 4 ml per 1mmol of hydrazone), the flask was flushed with argon and 3 equiv. of 1M BH3-THF complex was added at room temperature, followed by 3 hours of stirring. The progress of the reaction was checked by TLC and if some unreacted hydrazone was left, stirring was continued for an additional 45 min. After thefull conversion of hydrazone EtOH (10 ml) was added to the reaction mixture (Caution: Liberation of hydrogen) and the obtained mixture was refluxed for 1 hour. After cooling to room temperature the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with saturated NaHCO3 solution, water and saturated NaCl solution. The aqueous phase was extracted twice with ethyl acetate, the extracts were washed with saturated NaCl solution, combined with the organic phase, dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel by using ethyl acetate/light petroleum 1:1 or 1:2 mixtures or pure ethyl acetate as eluent. For the exact information about the eluent used for monitoring reaction progress and chromatographic purifications, see the Rf value for each compound.

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; Mastitski, Anton; Niinepuu, Siret; Haljasorg, Toiv; Jaerv, Jaak; Organic Preparations and Procedures International; vol. 50; 4; (2018); p. 416 – 423;,
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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. 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, A new synthetic method of this compound is introduced below., 450-88-4

Tris-(2-methoxy-4-fluorophenyl)phosphine (L4) preparation. Charge magnesium (Mg) turnings (1.18 g, 48.8 mmol) and five (5) mL THF under nitrogen into a 3-neck round-bottom flask equipped with a reflux condenser and heat the flask contents to 500C with a heating mantle. Add dropwise a solution of 2-bromo-5- fluoroanisol (5.00 g, 24.39 mmol) and 1 ,2-dibromoethane (0.51 g, 2.7 mmol) in THF (total volume of 15 mL) with stirring. Remove the heating mantle five (5) minutes after commencing the addition as the reaction heat becomes sufficient to maintain the reaction temperature. After completing the addition in about 50 minutes to yield a first mixture, reflux the first mixture for an additional 30 minutes to yield a brown solution. After allowing the brown solution to cool to room temperature, separate the brown solution from the unreacted Mg turnings by transferring the brown solution via a cannula into a 100 mL round-bottom flask under nitrogen. Cool the brown solution to -700C and add dropwise a solution Of PCl3 (1.038 g, 7.56 mmol) in seven (7) mL THF with stirring over a period of 30 minutes to yield a second mixture. Heat the second mixture to 500C and stir the second mixture for two (2) hours at 500C. After cooling flask contents to room temperature and transferring the flask into a glovebox, filter the second mixture and wash the filter with diethyl ether (20 mL) to obtain a filtrate. Remove volatiles from the filtrate under vacuum to yield a light brown solid. Dissolve this light brown solid in benzene under an inert nitrogen atmosphere to obtain a benzene solution and wash the benzene solution with deionized water (3 x 20 mL). Dry the organic layer over MgSO4 and then filter it to obtain a dry benzene solution. Remove benzene under vacuum to isolate an off-white solid, which is further purified by recrystallization from acetonitrile (1.60 g, 52.1 % yield). 1H NMR (C6D6): delta 2.99 (s, 3 H), 6.30-6.33 (m, IH), 6.49-6.52 (t of d, 3/HH = 8.2, 2.3, IH), 6.82-6.86 (m, IH). 31P NMR (C6D6, externally referenced using H3PO4): delta -38.9. 19F NMR (C6D6): -110.8 to -110.90 (m, IF).

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; DOW GLOBAL TECHNOLOGIES INC.; BRIGGS, John; PATTON, Jasson; VERMAIRE-LOUW, Sonet; MARGL, Peter; HAGEN, Henk; BEIGZADEH, Daryoosh; WO2010/19360; (2010); A2;,
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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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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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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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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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A common heterocyclic compound, 437-82-1, name is 2,6-Difluoroanisole, molecular formula is C7H6F2O, 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. 437-82-1.

Step 1. Preparation of 3,5-difluoro-4-methoxyacetophenone To a stirred suspension of AlCl3 (24.05 g, 180.40 mmol) in chloroform (300 mL, dried by passage through alumina) at 4 C. (ice bath) under nitrogen was added acetyl chloride (11.0 mL, 152.65 mmol) over 20 minutes. This chilled suspension was stirred at 0 C. for 30 minutes and 2,6-difluoro anisole was added dropwise over 30 minutes. The resulting suspension was warmed to room temperature and stirred overnight. The reaction was quenched by slowly pouring it into a rapidly stirred ice/water mixture. The water layer was extracted with methylene chloride (2*50 mL) and the organic phases were combined and concentrated in vacuo yielding a clear mobile oil. In a 50 mL round bottomed flask was added the above clear oil, DMF (25 mL), K2 CO3 (15 g). Methyl iodide (6 mL) was added and the suspension stirred at 45 C. under nitrogen overnight. water (1 mL) was added and the mixture was heated for an additional 14 hours. The crude reaction mixture was cooled to room temperature, diluted with water (250 mL) and extracted with diethyl ether (3*100 mL). The ether phase was washed with sodium bicarbonate saturated solution, potassium bisulfate (0.1N solution), dried over MgSO4, filtered and concentrated in vacuo yielding a clear mobile liquid. This liquid was distilled (30 C., 1 mm) yielding 12.5 g of a clear liquid which was a mixture of 3,5-difluoro-4-methoxyacetophenone and 3,5-difluoro-4-acetoxyacetophenone in an 85:15 ratio.

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

Reference:
Patent; G.D. Searle & Co.; US5756529; (1998); A;,
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