Month: October 2020

These common heterocyclic compound, 105529-58-6, name is 4-Bromo-2-fluoro-1-(trifluoromethoxy)benzene, 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. 105529-58-6

(Fifth stage) In 80 ml of THF was dissolved 8.0 g (30 mmol) of the 2-(3,5-difluorophenyl)-5-pentylpyrimidine described above, and cooled down to -60 C. under nitrogen gas atmosphere. To this solution was added dropwise 20 ml of 1.60 M solution of n-butyl lithium (32 mmol) in hexane while maintaining the condition that the temperature of the solution did not exceed -50 C., and then stirred at the same temperature for 1 hour. Subsequently, 64 ml of 0.5 M solution of zinc chloride (32 mmol) in THF was added dropwise to the reaction solution while maintaining the condition that the temperature of the solution did not exceed -50 C., warmed up to room temperature, and then stirred for 30 min. To this solution were added 0.5 g of tetrakistriphenylphosphine palladium and 8.3 g of 3-fluoro-4-trifluoromethoxybromobenzene, and heated to reflux for 3 hours. To the reaction solution was added 100 ml of water, and the product was extracted with toluene. The extract was washed with 3N-hydrochloric acid, saturated aqueous solution of sodium bicarbonate, and saturated aqueous solution of sodium chloride in turn, and dried over anhydrous magnesium sulfate. The solvent was distilled off. The residue was purified by silica gel column chromatography (eluent: heptane/toluene=1/1), and then recrystallized twice from heptane/ethyl acetate=1/1 to obtain 0.09 g (0.2 mmol) of 2-(4-(3-fluoro-4-trifluoromethoxyphenyl)-3,5-difluorophenyl)-5-pentylpyrimidine. Yield of this product from 2-(3,5-difluorophenyl)-5-pentylpyrimidine was 0.7%.

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 105529-58-6.

Reference:
Patent; Chisso Corporation; US6326065; (2001); B1;,
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In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 946-80-5, name is Benzyl Phenyl Ether belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 946-80-5

Preparation of 4-benzyloxyphenylsulfonyl chloride (24-2) STR187 To a 0 C. solution of sulfonyl chloride (1.9 mL, 23.8 mmol) in 2 mL of DMF was added 4.0 g (21.7 mmol) of benzyl phenyl ether (24-1). The resulting solution was then heated at 100 C. for 2 h. The reaction mixture was then cooled and poured onto crushed ice. The aqueous layer was extracted with CH2 Cl2 (x3). The combined organic extracts were dried (Na2 SO4) and concentrated. Column chromatography (95:5 Hexane/EtOAc) and trituration (hexane) of the pure fractions afforded 24-2 as a pink solid. 1 H NMR (CDCl3) delta 8.00 (d, J=7.8 Hz, 2H), 7.45 (m, 5H), 7.10 (d, J=7.8 Hz, 2H), 5.15 (s, 2H).

The synthetic route of 946-80-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck & Co., Inc.; US5872138; (1999); A;,
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1462-37-9,Some common heterocyclic compound, 1462-37-9, name is ((2-Bromoethoxy)methyl)benzene, molecular formula is C9H11BrO, 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. 4-(l-(2-(Benzyloxy)ethyl)-4-(trifluoromethyl)-lH-imidazol-2-yl)benzonitrile (0931) [00299] A mixture of Intermediate B-20 (1 g, 4.22 mmol), ((2-bromoethoxy)methyl)benzene (1.09 g, 5.07 mmol) and cesium carbonate (2.75 g, 8.44 mmol) in DMF (15 mL) was stirred for 18 h at 110 ¡ãC. After cooling to ambient temperature, the reaction mixture was poured into water (100 mL) and was then extracted with EtOAc (2 x 100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to afford 1.5 g (96percent) of 4-(l-(2-(benzyloxy)ethyl)-4-(trifluoromethyl)-lH-imidazol-2- yl)benzonitrile as a colorless oil. MS (ESI) m/z 371.8 [M+H]+.

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

Reference:
Patent; FORMA THERAPEUTICS, INC.; BUCKMELTER, Alexandre Joseph; IOANNIDIS, Stephanos; FOLLOWS, Bruce; GUSTAFSON, Gary; WANG, Minghua; CARAVELLA, Justin A.; WANG, Zhongguo; FRITZEN, Edward L.; LIN, Jian; (414 pag.)WO2017/87837; (2017); A1;,
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20781-20-8, A common compound: 20781-20-8, name is (2,4-Dimethoxyphenyl)methanamine, belongs to ethers-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

To a solution of compound 58 (6.6 g, 33.5 mmol) in dichloromethane (100 mL) were added DIPEA (8.65 g, 67 mmol), HOBt (5.4 g, 36.85 mmol) and EDCI (9.6 g, 50.3 mmol). After about 15 min stirring, to the homogeneous reaction mixture was added a solution of 2,4-dimethoxybenzyl amine (5.6 g, 33.5 mmol) in dichloromethane (50 mL) dropwise under nitrogen atmosphere. The resulting mixture was stirred under nitrogen atmosphere at room temperature for 16h. The reaction mixture was washed successively with IN NaOH (100 mL), water (100 mL) and brine (100 mL). The organic phase was then dried over Na2S04 and evaporated to give a crude solid product 59 that crystallized from ethyl ether. Filtration and open air suction drying afforded an off-white solid pure product 9.8g (96%), (MS: [M+l] = 347).

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, (2,4-Dimethoxyphenyl)methanamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; AGENEBIO, INC.; MEKONNEN, Belew; BUTERA, John, A.; HUANG, Jianxing; WO2015/95783; (2015); A1;,
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134364-69-5, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 134364-69-5, name is 2,3-Difluoroanisole belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

In 0 C next, the anhydrous aluminum chloride (1.82g, 13mmol) is added to 5-bromo-2-chlorobenzene formyl chloride 12b (3.4g, 13 . 4mmol, see example 12 step 1) and 1,2-difluoro-3-methoxybenzene 14b (2.4g, 16 . 7mmol) in dichloromethane (40 ml) in a mixed solution, in 0 C reaction under 16 hours. Maintain 0 C using hydrochloric acid solution (4 ml, 8mmol, 2M) quenching the reaction, the resulting mixture of natural temperature raising to room temperature, with methylene chloride (40 ml ¡Á 4) extraction, combined with the phase. The organic phase is dried with anhydrous sodium sulfate, filtered, filtrate concentrated to obtain title compound 14c crude product of (5.4g, yellow liquid), yield: 96.4%. The crude product is directly used for the next step synthesis.

The synthetic route of 2,3-Difluoroanisole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong East Sunshine Pharmaceutical Co., Ltd; Gu, Zheng; Wen, Jiaping; Tang, Wanjun; Wang, Weihua; Deng, Bingchu; Wu, Wuyong; Qu, Tong; (100 pag.)CN105461762; (2016); A;,
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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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