Category: ethers-buliding-blocks

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 5414-19-7 as follows. 5414-19-7

Under argon, 100 mg (0.30 mmol) of (4S)-1-(4-aminophenyl)-8-methoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 53.2A) were dissolved in 4 ml of N,N-dimethylacetamide, and 103 mg (0.44 mmol) of 1-bromo-2-(2-bromoethoxyl)ethane and 0.1 ml (0.59 mmol) of diisopropylethylamine were added. The mixture was stirred at 120 C. for three days. The reaction was added to water and extracted three times with ethyl acetate. The solvent was removed on a rotary evaporator and the residue was purified by flash chromatography. This gave 95 mg (79% of theory) of the desired product. [2019] UPLC/MS (Method 2): Rt=1.18 min; m/z=409 (M+H)+ [2020] 1H-NMR (300 MHz, CDCl3): delta=1.07 (d, 3H), 2.72 (dd, 1H), 2.86 (d, 3H), 2.95 (dd, 1H), 3.25 (m 4H), 3.71 (s, 3H), 3.89 (m, 4H), 5.19-5.30 (m, 1H), 6.12 (m, 1H), 6.67 (d, 1H), 6.89 (dd, 1H), 6.92 (d, 2H), 7.15 (d, 1H), 7.51 (d, 2H).

According to the analysis of related databases, 5414-19-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; Siegel, Stephan; Baeurle, Stefan; Cleve, Arwed; Haendler, Bernard; Fernandiez-Montalvan, Amaury Ernesto; Moenning, Ursula; Krause, Sabine; Lejeune, Pascale; Schmees, Norbert; Busemann, Matthias; Holton, Simon; Kuhnke, Joachim; US2015/203483; (2015); A1;,
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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. 5414-19-7, name is 1-Bromo-2-(2-bromoethoxy)ethane belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 5414-19-7

[0971] To a DMF (9 mL) solution of Part E (1.08 g, 2.71 mmol) was added K2CO3 (1.12 g, 8.16 mmol), 18-crown-6 (0.21 g, 0.80 mmol), and bis(2-bromoethyl)ether (0.37 mL, 2.9 mmol). The slurry was stirred at 60C. for 72 hr. Additional bis(2-bromoethyl)ether was added at 24 hr (0.4 mmol) and 48 hr (1.2 mmol). The solvent was stripped in vacuo, and the residue was partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was separated, dried over MgSO4, and evaporated to an oil. Recrystallization from diethyl ether produced 0.88 g (69%) of the desired compound in the form of a white solid. LCMS: m/z=469.2 (M+H).

The synthetic route of 5414-19-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Barta, Thomas E.; Becker, Daniel P.; Bedell, Louis J.; Boehm, Terri L.; Brown, David L.; Carroll, Jeffery N.; Chen, Yiyuan; Fobian, Yvette M.; Freskos, John N.; Gasiecki, Alan F.; Grapperhaus, Margaret L.; Heintz, Robert M.; Hockerman, Susan L.; Kassab, Darren J.; Khanna, Ish K.; Kolodziej, Stephen A.; Massa, Mark A.; McDonald, Joseph J.; Mischke, Brent V.; Mischke, Deborah A.; Mullins, Patrick B.; Nagy, Mark A.; Norton, Monica B.; Rico, Joseph G.; Schmidt, Michelle A.; Stehle, Nathan W.; Talley, John J.; Vernier, William F.; Villamil, Clara I.; Wang, Lijuan J.; Wynn, Thomas A.; US2005/9838; (2005); A1;,
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Some common heterocyclic compound, 854391-95-0, name is Bis(4-methoxybenzyl)amine hydrochloride, molecular formula is C16H20ClNO2, 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. 854391-95-0

A solution of 2-(benzylthio)-5-chloropyrazine (0.916 g, 3.87 mmol) in DCM (15 mL, 233 mmol) was treated with water (1.5 mL) and the resultant suspension was cooled to between -5 and o C. Sulfuryl chloride (2.2 mL, 26.2 mmol) was added and the reaction mixture was stirred for 2 hours maintaining the temperature between -5 and o C. A slurry of ice/water (10 mL) was added and the organic phase was collected. The aqueous phase was extracted with DCM (2 x 10 mL) and the combined organic extracts were dried (MgS04) and concentrated in vacuo to afford crude intermediate 5- chloropyrazine-2-sulfonyl chloride as a pale yellow liquid (1.198 g). (1370) A suspension of bis(4-methoxybenzyl)amine hydrochloride (1.198 g, 4.08 mmol) and TEA (1.2 mL, 8.61 mmol) in DCM (15 mL) at o C was treated with a solution of 5- chloropyrazine-2-sulfonyl chloride (0.824 g, 3.87 mmol) in DCM (5 mL) dropwise. The resultant solution was stirred at o C for 15 minutes and then allowed to warm to room temperature for 16 hours. A saturated aqueous NH4C1 solution (10 mL) was added and the organic phase was collected. The aqueous phase was extracted with DCM (2 x 10 mL) and the combined organic extracts were dried (MgS04) and concentrated in vacuo. The crude product was purified by chromatography on silica gel (24 g column, 0-30% EtOAc/isohexane) to afford the title compound (1.312 g, 77 %) as a white solid. (1371) NMR (CDCI3) delta 8.78 (d, J = 1.4 Hz, lH), 8.46 (d, J = 1.4 Hz, lH), 7.11 – 7.07 (m, 4H), 6-79 – 6.75 (m, 4H), 4-43 (s, 4H), 3-79 (s, 6H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 854391-95-0, its application will become more common.

Reference:
Patent; INFLAZOME LIMITED; COOPER, Matthew; MILLER, David; MACLEOD, Angus; VAN WILTENBURG, Jimmy; THOM, Stephen; ST-GALLAY, Stephen; SHANNON, Jonathan; (352 pag.)WO2019/8025; (2019); A1;,
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20781-20-8, 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. 20781-20-8, name is (2,4-Dimethoxyphenyl)methanamine, This compound has unique chemical properties. The synthetic route is as follows.

( 2R,6R, 1 lR)-tert-butyl 8-(( 2,4-dimethoxybenzyl)carbamoyl)-6, 11 -dimethyl-1, 2,5,6- tetrahydro-2, 6-methanobenzo[d]azocine-3( 4H)-carboxylate Chemical Formula: C 38N205 Exact Mass: 494.28 Molecular Weight: 494.62 To a solution of (2R,6R,1 lR)-tert-butyl 6,11 -dimethyl- 8- (((trifluoromethyl)sulfonyl)oxy)-l,2,5,6-tetrahydro-2,6-methanobenzo[d]azocine- 3(4H)-carboxylate (5.32 g, 11.8 mmol) in degassed dimethyl sulfone (50 mL), was added N-hydroxysuccinimide (2.73 g, 23.7 mmol), palladium acetate (265 mg, 1.18 mmol), triethylamine (3.3 mL, 23.7 mmol) and 4,5-bis(diphenylphosphino)-9,9- dimethylxanthene (683 mg, 1.18 mmol). The reaction mixture was heated with carbon monoxide (latm) at 70C overnight. The reaction mixture was cooled to ambient temperature and 2,4-dimethoxybenzylamine (2.17 mg, 13.0 mmol) added. The mixture was stirred for 2 hours diluted with ethyl acetate (800 mL), and filtered through celite. The organic solution was washed twice with water (800 mL), brine (300 mL), and dried (MgS04). Filtration and removal of the solvent under reduced pressure gave crude material that was purified by silica chromatography (EtOAc(l):heptanes(l)) to give (2R,6R,llR)-tert-butyl 8-((2,4- dimethoxybenzyl)carbamoyl)-6, 11 -dimethyl- 1 ,2,5,6-tetrahydro-2,6- methanobenzo[d]azocine-3(4H)-carboxylate (4.0 g, 68% yield); LC/MS(M+H)+ = 495.3.

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; ALKERMES PHARMA IRELAND LIMITED; BLUMBERG, Laura, Cook; DEAVER, Dan; EYERMAN, David; WO2014/190270; (2014); A1;,
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Adding some certain compound to certain chemical reactions, such as: 5111-65-9, name is 2-Bromo-6-methoxynaphthalene, 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 5111-65-9. 5111-65-9

After 2-bromo-6-methoxynaphthalene (200 mg, 0.844 mmol), sodium azide (110 mg, 1.69 mmol), proline (126 mg, 1.10 mmol), and copper(I) oxide (121 mg, 0.844 mmol) were added to degassed DMSO (1.7 ml), this mixture was heated at 100 C. for 11 hours. The reacted solution was cooled to room temperature, and then ethyl acetate and water were introduced thereto. The mixed solution was filtered to remove solid, and then the filtered liquid was layer-separated. The separated organic layer was washed with an aqueous solution of saturated sodium bicarbonate, dried over sodium sulfate, and then concentrated in vacuo. The concentrated solution was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give an orange solid of 6-methoxynaphthalene-2-amine (77.9 g, 0.450 mmol, 53.3%). 1H-NMR (CDCl3, Varian 400 MHz): delta3.73 (2H, brs), 3.88 (3H, s) , 6.93-6.97 (2H, m) , 7.04-7.08 (2H, m) , 7.51 (1H, d, J=8.8 Hz), 7.57 (1H, d, J=8.8 Hz)

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 2-Bromo-6-methoxynaphthalene.

Reference:
Patent; COLLEGE OF MEDICINE POCHON CHA UNIVERISTY INDUSTRY- ACADEMIC COOPERATION FOUNDATION; CHAMEDITECH CO., LTD.; Yoon, Tae Jong; Chung, Kwang Hoe; Seo, Jeongbeob; Kang, Sin Wook; Lee, Kwang Hyuong; Kwon, Yong Su; Jeon, Hye Sun; Lee, Chae Woon; Kim, Jin sung; US2018/327357; (2018); A1;,
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405-06-1, Adding some certain compound to certain chemical reactions, such as: 405-06-1, name is 2-Fluoro-4-methoxy-1-methylbenzene, 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 405-06-1.

A 10 mL oven-dried Schlenk tube was charged with magnesium (57.6 mg, 2.4 mmol) and anhydrous THF (1.5 mL), 5 drops of diisobutylaluminium hydride (DIBAL) was added and stirred for 5 min to activate magnesium. 2-bromo-1,3,5-triisopropylbenzene (566 mg, 2 mmol) was added potion-by-potion with vigorous stirring. The tube was capped with a rubber septum and was heated to 70 C. for 2 h (A). In another 10 mL oven-dried Schlenk tube was charged with 2-fluoro-4-methoxy-1-methylbenzene (140 mg, 1 mmol) and anhydrous THF (3.5 mL). The tube was cooled to -78 C. and 1.6 M n-BuLi solution in hexane (0.64 mL, 1 mmol) was added dropwise over 10 min under vigorous stirring. The mixture was stirred at -78 C. for 40 min (B). A was transferred into to B by syringe over 15 min at -78 C. An additional 1 mL of THF was used to rinse the reaction and was also transferred to B. The combined reaction mixture was stirred at -78 C. for another 1 h and then slowly warmed to room temperature and vigorously stirred for overnight. At this time, the mixture was cooled to 0 C. using ice bath, and iodine (762 mg, 3 mmol) in 4 mL anhydrous THF was added drop-wise over 5 min, then the reaction mixture was stirred for 30 min, and then warmed to stir at room temperature for 2 h. Then, the mixture was quenched with saturated Na2S2O3 (aq.) solution until the red color of bromine disappeared. The aqueous phase was extracted with Et2O (10 mL¡Á3) and the combined organic phases were dried over anhydrous MgSO4. After concentration, the crude product was purified by silica gel chromatography (EtOAc/petroleum ether=1/20) followed by crystallization in methanol to get a white solid (185 mg, 34%), labeled as 2MeO-SMeTIP-I. 1H NMR (600 MHz, Chloroform-d) delta 7.46-7.29 (m, 4H), 7.25 (dd, J=8.3, 0.8 Hz, 2H), 7.12 (s, 1H), 6.78 (d, J=8.3 Hz, 1H), 3.97 (s, 3H), 2.73-2.59 (m, 1H), 2.54 (p, J=6.8 Hz, 1H), 2.37 (p, J=6.8 Hz, 1H), 2.13 (s, 3H), 1.37 (d, J=7.0 Hz, 3H), 1.28 (d, J=6.8 Hz, 3H), 1.18-1.07 (m, 6H), 0.88 (d, J=7.2 Hz, 3H), 0.82 (d, J=7.2 Hz, 3H) ppm. 13C NMR (151 MHz, Chloroform-d) delta 156.49, 147.77, 146.49, 144.69, 141.28 (d, J=23.7 Hz), 139.64, 138.22, 131.97, 131.47, 130.62, 130.17, 129.81, 127.88, 126.87 (d, J=11.2 Hz), 126.38, 120.38 (d, J=35.2 Hz), 109.03, 56.39, 34.27, 32.38, 30.78, 30.26, 29.50, 24.63 (d, J=5.6 Hz), 24.47, 24.29, 24.22, 24.11, 23.42 (d, J=11.7 Hz), 21.54 ppm.

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 405-06-1.

Reference:
Patent; Agency for Science, Technology and Research; Johannes, Charles W.; Robins, Edward G.; Jong, Howard; Lim, Yee Hwee; Chia, Saei Weng; Yang, Yong; Podichetty, Anil; (84 pag.)US2016/207034; (2016); A1;,
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19056-40-7, 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. 19056-40-7 name is 4-Bromo-3-methoxyaniline, 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.

A solution of BBr3 in dichloromethane (1.0 M, 12 mL,12 mmol) was added slowly to a solution of 4-bromo-3-methoxyaniline (800 mg, 3.96 mmol) in methylene chloride(15 mL) at 0C. The resulting brown solution was warmed toroom temperature and stirred for 24 h. After saturated aqueousNaHCO3 (30 mL) was added at 0C, the solution was extractedwith EtOAc (20 mL ¡Á 3). The combined organic layer wasdried with anhydrous Na2SO4, filtered and concentrated invacuum. The residue was purified by flash chromatographyover silica gel (petroleum-EtOAc = 2 : 1) to give 5-amino-2-bromophenol (665 mg, 88%). To a solution of 5-amino-2-bromophenol (55 mg, 0.29 mmol)and triethylamine (53 muL, 0.38 mmol) in tetrahydrofuran (THF)(3 mL) was added slowly benzoyl chloride (0.32 mmol) at 0C.The reaction mixture was then stirred at room temperature for30 min. After the reaction was quenched with water (10 mL),the solution was extracted with EtOAc (10 mL ¡Á 2). The combinedorganic layer was dried over anhydrous Na2SO4, filteredand concentrated in vacuum. The residue was purified bycolumn chromatography to afford the product 3 (74 mg, 87%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-3-methoxyaniline, and friends who are interested can also refer to it.

Reference:
Article; Liang, Jie; Tang, Yun-xiang; Tang, Xiang-zheng; Liang, Hua-ju; Gao, Yamin; Fang, Cuiting; Zhang, Tian-yu; Yan, Ming; Chemical and Pharmaceutical Bulletin; vol. 67; 4; (2019); p. 372 – 381;,
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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. 52411-34-4, name is 1,2-Bis(o-aminophenoxy)ethane, This compound has unique chemical properties. The synthetic route is as follows., 52411-34-4

Then, triphenylphosphine dibromide (0.11 mol) and 150 ml of 1,2-dichloroethane were fed to a reactor equipped with a stirrer, a heater and a dropping funnel in an N2 atmosphere and stirred. A solution obtained by dissolving the intermediate product B (0.05 mol) and triethylamine (0.25 mol) in 50 ml of 1,2-dichloroethane was gradually added dropwise to the resulting mixture at 25 C. After the end of addition, a reaction was carried out at 70 C. for 5 hours. Thereafter, the reaction solution was filtered, and the filtrate was separated with 100 ml of water 5 times. An organic layer was dehydrated with 5 g of sodium sulfate and 1,2-dichloroethane was removed under reduced pressure to obtain an intermediate product C (triphenylphosphine derivative).

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; TEIJIN LIMITED; Matsuno, Yuichi; Mitsunaga, Masaki; Oda, Jitsuo; Furuki, Masatsugu; Shoji, Shinichiro; Kitamura, Takuro; Shibata, Yoshitaka; (51 pag.)US9650350; (2017); B2;,
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101-55-3, 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. 101-55-3, name is 1-Bromo-4-phenoxybenzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

4B. Alternative Preparation of (5) where R 5 is 4-(4-Bromophenoxy)phenyl A solution of 4-bromodiphenyl ether (50 g, 200.7 mmol) in methylene chloride (118 ml) was cooled to 0C and chlorosulfonic acid (14.7 ml, 220.8 mmol) was added dropwise over a 20 minute period. The solution was stirred an additional 10 minutes, warmed to room temperature and stirred an additional 1 hour. To this mixture was added oxalyl chloride (23.6 ml, 270.9 mmol), followed by N,N-dimethylformamide (1.5 ml) as a catalyst, and the mixture refluxed for 2 hours. The mixture was cooled to room temperature, and additional oxalyl chloride (23.6 ml, 270.9 mmol) was added, the mixture refluxed for 3 hours, cooled to room temperature and stirred 12 hours more. The solution was concentrated to an oil, azeotroped several times using methylene chloride and put under high vacuum (1 torr) for several hours until the mixture had completely solidified. This mixture was immediately dissolved in methylene chloride (160 ml) which was added dropwise to a solution of triphenylphosphine (157.0 g, 602 mmol) in methylene chloride (160 ml) containing N,N-dimethylformamide (4 ml, 52.2 mmol). The mixture was stirred 2 hours, diluted with 1M aqueous hydrochloric acid (300 ml) and stirred for 1 hour. The aqueous layer was separated, extracted with methylene chloride (200 ml), and the organic layers were combined, washed with 200 ml of brine, dried (MgSO4) and concentrated in vacuo.The resulting solid was further purified through trituration with 750 ml of hexane. The solid was then dissolved in 750 ml of diethyl ether, extracted with 2M aqueous sodium hydroxide (2 x 350 ml), and the basic aqueous layer back extracted using diethyl ether (2 x 400 ml). The aqueous layer was adjusted to pH 2, extracted with diethyl ether (3 x 200 ml) and the combined organic layers dried (MgSO4) and concentrated to afford 4-(4-bromophenoxy)thiophenol (45.6 g, 81%). 1H-NMR (CDCl3) delta 3.43 (s, 1H), 6.86 (d, J= 8.9 Hz, 2H), 6.89 (d, J= 8.6 Hz, 2H), 7.28 (d, J= 8.6 Hz, 2H), 7.43 (d, J= 8.9 Hz, 2H).

The synthetic route of 1-Bromo-4-phenoxybenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; AGOURON PHARMACEUTICALS, INC.; EP780386; (1997); A1;,
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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. 454-90-0 name is 3-(Trifluoromethyl)anisole, 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. 454-90-0

General procedure: (b) For isolations of the major products, copper(I) chloride (0.248 g, 2.5 mmol) and Mg powder (0.486 g, 20 mmol) were stirred in DMI (20 ml, 10 ml for 7i, 7j, 7k) and TMS-Cl (5 ml, 40 mmol) for 15 min under an argon atmosphere. Then, a benzotrifluoride derivative 6 (5 mmol) was added dropwise over 5 min into the dark suspension. The solution was stirred for additional time (see Table 2), keeping the temperature 25 C (bath temperature, 50 C for 7i, 7j, 7k). After addition of 5 ml of hexane, Mg-Cu was removed by decantation and the suspension was simultaneously extracted with hexane (5 ml¡Á5). Then, the combined hexane layer was washed with 10 wt % HCl aq and brine. After drying over sodium sulfate, purification by column chromatography on silica gel (hexane eluent) and distillation afforded the product.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-(Trifluoromethyl)anisole, and friends who are interested can also refer to it.

Reference:
Article; Utsumi, Shinya; Katagiri, Toshimasa; Uneyama, Kenji; Tetrahedron; vol. 68; 4; (2012); p. 1085 – 1091;,
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