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 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,
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Some common heterocyclic compound, 5905-69-1, name is 1-Bromo-4-(difluoromethoxy)benzene, molecular formula is C7H5BrF2O, 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. 5905-69-1

Piperidine-4-carboxylic acid ethyl (3.52mL, 22.9mmol), and 1-Bromo-4- (difluoromethoxy) benzene (4.25g, 19.1mmol) of TorrEne (122 mL) to the solution, sodium tert- butoxide (2.29g, 23.8mmol), palladium acetate (II) (428mg, 1.91mmol), and, tri -tert- butyl phosphine (370muL, 1.52mmol) was added, and 30 minutes at 80 And the mixture was stirred. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, the resulting organic layer was washed with saturated brineAfter, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Siri resulting residue wasGel column chromatography [elution solvent: hexane / ethyl acetate = 100 / 0-90Purification by / 10], the title compound (3.17 g, yield: 56%) was obtained.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5905-69-1, its application will become more common.

Reference:
Patent; Daiichi Sankyo company limited; Sato, Rie; Kobayashi, Katsuhiro; Kaneko, Toshio; (188 pag.)JP2015/113323; (2015); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

19056-40-7, These common heterocyclic compound, 19056-40-7, name is 4-Bromo-3-methoxyaniline, 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.

Under an atmosphere of nitrogen, in a 100 mL round-bottomed flask at 0¡ã C., 4-bromo-3-methoxyaniline (2 g, 9.9 mmol) and KOH (6.93 ml, 13.9 mmol) were combined with dichloromethane (30 ml) to give a light brown solution. Then 4-bromobutanoyl chloride (1.84 g, 1.15 ml, 9.9 mmol) was added. The reaction was stirred for 1 h at RT. The reaction mixture was poured into 50 ml dichloromethane and extracted with water (3*20 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in 30 ml dichloromethane. Then tetrabutylammonium bromide (63.8 mg, 198 mumol) and KOH (50percent, 6 ml) were added. The reaction was stirred for 1 h at RT. The reaction mixture was poured into dichloromethane (50 ml) and extracted with water (3*20 ml). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 50 g, 20percent to 50percent EtOAc in heptane). The title compound was obtained as a off-white crystalline (1.92 g, 71.8percent). MS (m/e)=272.1 [M+H]+.

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 19056-40-7.

Reference:
Patent; Hoffmann-La Roche Inc.; Jakob-Roetne, Roland; Wichmann, Juergen; Peters, Jens-Uwe; Jagasia, Ravi; (33 pag.)US2016/326150; (2016); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

5111-65-9,Some common heterocyclic compound, 5111-65-9, name is 2-Bromo-6-methoxynaphthalene, molecular formula is C11H9BrO, 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 21.2: 6-methoxy-naphthalen-2-ylamine A solution of 2-bromo-6-methoxy-naphthalene (237 mg, 1 mmol), Pd (dba)2 mg, 0.05 mmol), tri-t-buthylphosphonium tetrafluoroborate (14 mg, 0.05 mmol), and lithium bis (trimethylsilyl)amide (1 M in hexane, 1.1 mL, 1.1 mmol) is stirred in toluene (2.5 mL) under argon for 6 h. The reaction mixture is taken in diethyl ether (20 mL), and quenched with 1 M HCI. The organic phase is extracted with water, the combined aqueous phases are treated with 1 M sodium hydroxide and extracted with DCM. The combined organic phases are dried over magnesium sulfate, the solvent is evaporated in vacuo and the residue is purified by column flash chromatography on silica gel (ethyl acetate) to afford 6-methoxy- naphthalen-2-ylamine (110 mg, 64 %), HPLC tR : 3.07, (M+H) + = 173.9.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-6-methoxynaphthalene, its application will become more common.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2005/97135; (2005); A2;,
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321-28-8, Adding some certain compound to certain chemical reactions, such as: 321-28-8, name is 1-Fluoro-2-methoxybenzene, 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 321-28-8.

Step 1: Preparation of 3′-fluoro-4′-methoxy-acetophenone. acetyl chloride (51.0 g, 0.65 mol) was added dropwise to a stirred solution of aluminum chloride (80.0 g, 0.6 mol) and chloroform (750 ML), maintaining the temperature between 5-10 C. The mixture was stirred for 10 minutes at 5 C. before the dropwise addition of 2-fluoroanisole (62.6 g, 0.5 mol).. The mixture was stirred at 0-10 C. for 1 hour and poured into ice (1 L).. The resultant layers were separated and the aqueous layer was extracted with dichloromethane (2*250 ML).. The combined organic layers were washed with water (2*150 ML), dried over anhydrous MgSO4, filtered and concentrated in vacuo to a volume of 300 ML. Hexanes were added and a white solid formed which was isolated by filtration and air dried.. This material was recrystallized from a mixture of dichloromethane and hexanes to afford (77.2 g, 92%) of material suitable for use in the next step: mp 92-94 C.

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 321-28-8.

Reference:
Patent; G. D. Searle & Co.; US6342510; (2002); B1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

35896-58-3, name is 1,2,3,4-Tetramethoxy-5-methylbenzene, 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. 35896-58-3

2,3,4,5-Tetramethoxytoluene 3 (2.1 g, 10 mmol) and NaBr (1.1 g, 10 mmol) were dissolved in AcOH (5 mL), a solution of 30% H2O2 (1.2 mL, 10 mmol) was added dropwise over 5 min at room temperature. The mixture was stirred and heated at 40 C for 1 h and quenched with H2O( 5 mL) and extracted with diethyl ether (3 ¡Á 30 mL). The combined organic phases were washed with saturated NaHCO3(3 ¡Á 10 mL) until pH 7, then dried over anhydrous Na2SO4,and evaporated under reduced pressure to give yellow oil 4 (2.9 g) in quantatitive yield. 1H NMR (400 MHz, CDCl3) delta 3.92 (s, 3H, OCH3), 3.91(s, 3H, OCH3), 3.85 (s, 3H, OCH3), 3.79 (s, 3H, OCH3),2.30 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3)delta 148.3, 147.2, 146.3,145.5, 127.3, 114.3, 61.4 (OCH3), 61.1 (OCH3), 60.9(OCH3), 60.8 (OCH3), 15.9 (CH3). GC-MS (EI): m/z = 290.

Statistics shows that 35896-58-3 is playing an increasingly important role. we look forward to future research findings about 1,2,3,4-Tetramethoxy-5-methylbenzene.

Reference:
Article; Qiu, Yong-Fu; Lu, Bin; Yan, Yi-Yu; Luo, Wan-Yue; Wang, Jin; Hu, Xiao; Chemical Papers; vol. 73; 11; (2019); p. 2745 – 2748;,
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103-50-4, 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. 103-50-4 name is Benzyl ether, 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: To a sealed tube containing the respective azobenzene 1 (0.25 mmol), dibenzyl ether 2 (0.75 mmol), Pd(OAc)2 (0.025 mmol), and DCE/AcOH (1:1, v/v, 1 mL in all) was added TBHP (1.5 mmol). After stirring vigorously at 60 C for 12 h, the mixture was evaporated under vacuum. The corresponding product 3 was isolated by silica gel column chromatography with a PE/EtOAc mixture as eluent.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Benzyl ether, and friends who are interested can also refer to it.

Reference:
Article; Hong, Gang; Aruma, Alfred Njasotapher; Zhu, Xiaoyan; Wu, Shengying; Wang, Limin; Synthesis; vol. 48; 8; (2016); p. 1147 – 1158;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

The chemical industry reduces the impact on the environment during synthesis 6346-09-4, name is 4,4-Diethoxybutan-1-amine, I believe this compound will play a more active role in future production and life. 6346-09-4

To a solution of commercially available 4-aminobutyaldehyde diethyl acetal (21)[1] (5.00 g, 31.0 mmol) in THF (75 mL) was added TEA (6.50 mL, 4.70 g, 46.5 mmol) at 0-5 C (ice-bath temperature). The mixture was allowed to stir for 5 min, and treated with a solution of Boc2O (6.76 g, 31.0 mmol) in THF (30 mL) drop-wise. The reaction mixture was stirred at 0-5 C for 30 min and allowed to warm to RT.and stir for 3 h. The mixture was transferred to a separatory funnel and partitioned with H2O (100 mL) and EtOAc (200 mL). The organic layer was separated, dried (anhydrous Na2SO4), filtered and concentrated to afford 7.71 g (95% yield) of compound 22 as a viscous slightly yellow oil: 1H NMR (400 MHz,CDCl3) delta 4.63 (bs, 1H), 4.46 (t, J = 5.39 Hz, 1H), 3.55 (ABq of q, J = 9.32, 7.14 Hz, Dn = 62.10 Hz, 4H), 3.12 (q, J = 6.40 Hz, 2H), 1.65 – 1.60 (m, 2H), 1.57 – 1.50 (m, 2H), 1.42 (s, 9H), 1.18 (t, J = 6.90 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) delta 156.10, 102.47, 77.83, 60.99, (BocNHCH2- obscured by DMSO solvent peak ), 31.18, 28.78, 25.36, 15.83. HRMS ESI-TOF (m/z) = 284.1814 (284.1832 calculated for C13H27NO4Na) [M+Na].

The chemical industry reduces the impact on the environment during synthesis 6346-09-4. I believe this compound will play a more active role in future production and life.

Reference:
Article; Omran, Anahid; Eslamimehr, Shakiba; Crider, A. Michael; Neumann, William L.; Bioorganic and Medicinal Chemistry Letters; vol. 28; 10; (2018); p. 1897 – 1902;,
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Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 103-50-4, name is Benzyl ether, 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 103-50-4, 103-50-4

General procedure: To a stirred solution of ether (1.0 mmol) in AcOH (6 mL), was added 30 mol % of BF3¡¤Et2O followed by the addition of cyanamide (1.0 mmol). The reaction mixture was refluxed at an elevated temperature (40-50 C) till the completion of the reaction as monitored by TLC. Upon complete consumption of the cyanamide, the reaction medium was diluted with EtOAc (15 mL). The organic layer was washed with water followed by 5% NaHCO3 (2 ¡Á 5 mL), water (2 ¡Á 5 mL), and brine (5 mL). The organic layer was then dried over anhydrous Na2SO4 and the solvent was evaporated in vacuo to afford the crude which was then purified through silica gel column chromatography (30-40% EtOAc/hexane).

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, Benzyl ether, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Panduranga, Veladi; Basavaprabhu; Sureshbabu, Vommina V.; Tetrahedron Letters; vol. 54; 8; (2013); p. 975 – 979;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

929-75-9, 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. 929-75-9 name is 1,11-Diamino-3,6,9-trioxaundecane, 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.

N-i^e-Dichlorotl^^Jtriazin^-y -HO-dimethyl-hydroxylamine (XXX) (1.63 g, 7.8 mmol) in EtOH (100 mL) was added to 2,2′-(2,2*-oxybis(ethane- 2,l-diyl)bis(oxy))diethanamine {Org. Biomol. Che . 2005, 3:2255-61) (1.5 g, 7.8 mmol) and DIPEA (2.01 g, 15.6 mmol). The reaction was heated at 100 C for 3 h, after which time the solvent was removed under reduced pressure. The residue was dissolved in EtOAc (200 mL), washed with water (2 x 100 mL) and then with a brine solution (100 mL) and lastly dried over Na2S0 . The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (DCM MeOH=50/l to 20/1) to yield N-(5,8,l l-trioxa-2, 14,16,18,19- pentaazabicyclo[l 3.3.1 ]nonadeca-l(l 8), 15( 1 ), 16( 17)-trien-l 7-yl)-N,0- dimethylhydroxylamine (CXVII) (700 mg) as a colourless oil (yield 27%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,11-Diamino-3,6,9-trioxaundecane, and friends who are interested can also refer to it.

Reference:
Patent; GALLEON PHARMACEUTICALS, INC.; DAX, Scott, L.; WOODWARD, Richard; PENG, Sean; WO2012/74999; (2012); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem