Category: 111-95-5

Electric Literature of 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.

Compound 6-3 (5.3 g, 17.4 mmol) was dissolved in 1,4-dioxane (60 mL), followed by addition of compound 5-1 (4.85 g, 36.5 mmol), and potassium carbonate (4.9 g, 34.8 mmol) was added under stirring in batches, followed by stirring the reaction overnight at 70 C., TLC monitoring showed that the starting material 6-3 was completely reacted. The solvent was removed under reduced pressure to obtain a concentrated residue. The concentrated residue was dispensed with dichloromethane (20 mL), an appropriate amount of silica gel was added and the sample was stirred, spin-dried under reduced pressure and directly placed on a silica gel column for column chromatographic purification, with an eluent (dichloromethane:methanol=20/1-5/1) to obtain the target product 10-1 (2.2 g, 47.7%) as a pale yellow oil, LC-MS: m/z=266[M+H]+.

The synthetic route of 111-95-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shenzhen China Resources Gosun Pharmaceutical Co., Ltd.; Jiang, Xiongjie; Huang, Quanhua; Yang, Zhanao; (43 pag.)US2017/2028; (2017); 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. 111-95-5, name is Bis(2-methoxyethyl)amine, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 111-95-5

Into a 10-mL vial, was placed a solution of bis(2-methoxyethyl)amine (285.6 mg, 2.15 mmol, 3.00 equiv) in N,N-dimethylformamide (3 mL), and N,N-diisopropylethylamine (277 mg, 2.14 mmol, 2.99 equiv). This was followed by the addition of a solution of N-(3-(trifluoromethyl)benzyl)-2-(5-fluoro-2-nitrophenyl)isonicotinamide (300 mg, 0.72 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL). The resulting solution was stirred for 48 h at 80 C. in an oil bath. The reaction progress was monitored by LCMS. The resulting solution was diluted with 50 mL of water. The resulting solution was extracted with 3*50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2*70 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:5?1). The product was obtained as 270 mg (71%) of a yellow to green oil.

According to the analysis of related databases, 111-95-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ardelyx, Inc.; Lewis, Jason G.; Jacobs, Jeffrey W.; Reich, Nicholas; Leadbetter, Michael R.; Bell, Noah; Chang, Han-Ting; Chen, Tao; Navre, Marc; Charmot, Dominique; Carreras, Christopher; Labonte, Eric; (323 pag.)US9301951; (2016); B2;,
Ether – Wikipedia,
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These common heterocyclic compound, 111-95-5, name is Bis(2-methoxyethyl)amine, 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. 111-95-5

To the product from step 2 (1.00 g, 5.29 mmol) in ACN (20 mL) was added bis(2-methoxyethyl)amine (3.0 mL, 2.71 g, 20.3 mmol) and the reaction mixture was heated to 70 C. for 16 hours thereafter. The reaction was cooled and concentrated. The residue was partitioned with EtOAc and water. The organic layer was separated and the aqueous was extracted again with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated. Purification by flash column chromatography (SiO2, 10/1 hexanes-EtOAc to 1/1) afforded 950 mg (63% yield) of the desired adduct as a yellow solid: 1NMR (300 MHz, CDCl3) delta 7.47 (bs, 2H), 3.77 (t, J=5.7 Hz, 4H), 3.52 (t, J=5.4 Hz, 4H), 3.25 (s, 6H). 13C NMR (75 MHz, CDCl3) delta 154.7 (s), 152.0 (s), 120.9 (s), 119.5 (s), 95.8 (s), 71.0 (t), 59.1 (q), 50.0 (t).

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 111-95-5.

Reference:
Patent; MediBeacon Inc.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (52 pag.)US2019/125902; (2019); A1;,
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The chemical industry reduces the impact on the environment during synthesis 111-95-5, name is Bis(2-methoxyethyl)amine, I believe this compound will play a more active role in future production and life. 111-95-5

Intermediate B: /V,/V-bis(2-Methoxyethyl)hex-5-ynamide.12To a solution of hex-5-ynoic acid (7.1 1 g, 63.4 mmol), EDC.HCI (14.0 g, 72.9 mmol) and DMAP (387 mg, 3.17 mmol) in DCM (600 mL) at 0C was added bis{2- methoxyethyl)amine (9.3 mL, 63 mmol). The resulting mixture was warmed to RT for 20 hr and was then washed with hydrochloric acid (1 M, 2 x 500 mL) and water (500 mL). The organic layer was dried and evaporated in vacuo to afford the title compound, Intermediate B, as a yellow oil (16 g, 97%): 1H NMR (400 MHz, CDCI3) delta: 1 .88 (3H, m), 2.26 (2H, m), 2.49 (2H, m), 3.32 (6H, s), 3.51 (4H, m), 3.55 (4H, m)

The chemical industry reduces the impact on the environment during synthesis 111-95-5. I believe this compound will play a more active role in future production and life.

Reference:
Patent; RESPIVERT LIMITED; KING-UNDERWOOD, John; ITO, Kazuhiro; MURRAY, Peter John; HARDY, George; BROOKFIELD, Frederick Arthur; BROWN, Christopher John; WO2012/52753; (2012); A1;,
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111-95-5, 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. 111-95-5 name is Bis(2-methoxyethyl)amine, 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.

General procedure: An oven-dried 20 mL pressurevial was charged with monoester No.13a-f (1.0 eq) and dissolved in anhydrous DMF (0.5 mL/0.1mmol of the monoester). The corresponding amine (1.2 eq) was added, followed by HBTU (1.0 eq).The resulting solution was stirred at 0 C for 5 min, then TEA (2.0 eq) was added and stirring at 0 Cwas continued for 0.5 h. The resulting mixture was warmed to room temperature and stirring wascontinued for 2 h. The brownish solution was diluted with water (20 mL) and extracted with EtOAc(3 x 15 mL). Combined organic extracts were washed with water (15 mL), brine (15 mL), dried overanhydrous Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gelcolumn chromatography.

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

Reference:
Article; Zogota, Rimants; Kinena, Linda; Withers-Martinez, Chrislaine; Blackman, Michael J.; Bobrovs, Raitis; Pantelejevs, Teodors; Kanepe-Lapsa, Iveta; Ozola, Vita; Jaudzems, Kristaps; Suna, Edgars; Jirgensons, Aigars; European Journal of Medicinal Chemistry; vol. 163; (2019); p. 344 – 352;,
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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 111-95-5 as follows. 111-95-5

The product from step 1 (440 mg, 1.36 mmol) was dissolved in DMF (25 mL), treated with HOBt.H2O (624 mg, 4.08 mmol), and EDC.HCl (786 mg, 4.10 mmol) and stirred for 30 min at room temperature. Bis(2-methoxylethyl)amine (620 mL, 559 mg, 4.20 mmol) was added and the resulting mixture was stirred at room temperature for 16 h and concentrated. The residue was partitioned with water and EtOAc. The EtOAc layer was separated and the aqueous was extracted again with EtOAc. The combined organic layers were washed with 0.5 N HCl, saturated sodium bicarbonate, and brine. The organic layer was dried (Na2SO4), filtered and concentrated to afford 214 mg of 3-(bis(2-methoxyethyl)amino)-6-bromo-N2,N2,N5,N5-tetrakis(2-methoxyethyl)pyrazine-2,5-dicarboxamide (26% yield) as a brown oil: LCMS (5-95% gradient acetonitrile in 0.1% TFA over 10 min), single peak retention time=3.85 min on 30 mm column, (M+H)+=608.

According to the analysis of related databases, 111-95-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MediBeacon Inc.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (52 pag.)US2019/125902; (2019); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

A common compound: 111-95-5, name is Bis(2-methoxyethyl)amine, 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. 111-95-5

General procedure: General procedure B: To a mechanically stirred solution of bis(2-methoxyethyl)amine (39.96 g, 0.3 mol) in dichloromethane (100 mL), was added dropwise n-butyllithium (1.6 M in n-hexane, 187.5 mL, 0.3 mol) at -78 C under an argon atmosphere. After further stirring for 5 min, pentafluoroethanesulfonyl fluoride (2, 20.21 g, 0.1 mol) was added and the mixture was stirred for 1 h. Then the cryopump was removed, and allow the mixture stand at room temperature. The subsequent procedures exactly followed those in the procedure A.

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, 111-95-5, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Fu, Shi-Tao; Liao, Shuai-Ling; Nie, Jin; Zhou, Zhi-Bin; Journal of Fluorine Chemistry; vol. 147; (2013); p. 56 – 64;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 111-95-5, name is Bis(2-methoxyethyl)amine, This compound has unique chemical properties. The synthetic route is as follows., 111-95-5

(1)N’5′-[2-Chloro-4-(trifluoromethyl)phenyl]-N’5′-ethyl-2-(4-methoxybenzyl)-N’7′,N’7-bis(2-methoxyethyl)-2H-pyrazolo[4,3-d]pyrimidine-5,7-amine A mixture of 7-chloro-N-[2-chloro-4-(trifluoromethyl)phenyl]-N-ethyl-2-(4-methoxybenzyl)-2H-pyrazolo[4,3-d]pyrimidine-5-amine(a compound obtained in Reference Example 16) (75 mg), N,N-diisopropylethylamine(18.2 mg) and bis(2-methoxyethyl)amine(93.7 mg) in N-methylpyrrolidone(1.1 mL) was stirred at outside temperature of 110C under argon gas atmosphere overnight. After being cooled to room temperature, water and chloroform were added to the reaction mixture, the separated organic layer was washed with a saturated brine, dried over sodium sulfate and the solvent was evaporated under reduced pressure. The resulted residue was purified by using a silica gel column chromatography (hexane:ethyl acetate=10:1 to 5:2) to give the titled compound(84.3 mg) quantitatively as a pale yellow liquid. MS(APCI)m/z:593/595[M+H]+.

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; Mitsubishi Tanabe Pharma Corporation; EP1903045; (2008); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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 111-95-5 as follows. 111-95-5

Bis(2-methoxyethyl)amine (9.0 mL, 60.8 mmol, 1.8 eq.) was added dropwise to a solutionof PCl3 (3.0 mL, 34.3 mmol) in dry hexane (90 mL) under N2 at 0 C. The resulting white slurrywas stirred at 20 C for 1 h, filtered and washed with hexanes (3x 100 mL). The solvent wasremoved (rotavap) and the residue distilled under reduced pressure (125 C, 100 mmHg). Theproduct was isolated as a colorless clear liquid (5.14 g, 64%).Data for 29a:1H-NMR: (500 MHz, CDCl3)delta 3.33 (s, 6 H, OCH3), 3.49 (s, 8 H, 1-H, 2-H).13C-NMR: (125 MHz, CDCl3)delta 48.6 (d, J = 16.8 Hz), 58.9, 71.1 (d, J = 2.6 Hz).31P NMR: (200 MHz, CDCl3)delta -84.2.

According to the analysis of related databases, 111-95-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Boese, Dietrich; Denmark, Scott E.; Synlett; vol. 29; 4; (2018); p. 433 – 439;,
Ether – Wikipedia,
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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. 111-95-5, name is Bis(2-methoxyethyl)amine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 111-95-5

In a 100 ml eggplant type flask, 3.6 ml (25 mmol) of bis (2-methoxyethyl) amine,3.2 g (25 mmol) of phloroglucinol and 30 ml of THF were added and stirred. After 48 hours,The reaction was confirmed by TLC (SiO 2, developing solvent hexane: acetone = 1: 1), followed by extraction with chloroform, and the solvent was distilled off under reduced pressure to obtain a black viscous substance (yield 5.1 g, yield 86 %).

The synthetic route of 111-95-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Satoru: Yamagata University; Kido Junji; Sasabe Hisa Hiroshi; Sasaki Isamu; (15 pag.)JP6281975; (2018); B2;,
Ether – Wikipedia,
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