Category: ethers-buliding-blocks

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. 6346-09-4, name is 4,4-Diethoxybutan-1-amine belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 6346-09-4

Intermediate 145: 6-Chloro-N4-(4,4-diethoxybutyl>N2-methylpyridine-2,4- dicarboxamide (0902) (0903) To a solution of 2-chloro-6-(methylcarbamoyl)isonicotinic acid (2 g, 8.85 mmol) and HATU (3.70 g, 9.74 mmol) in DMF (20 mL) was added DIPEA (3.09 mL, 17.71 mmol) followed by 4,4- diethoxybutan-l-amine (1.68 mL, 9.74 mmol). The resulting solution was stirred at rt for 16 h. Water (60 mL) and EtOAc (60 mL) were added and the layers separated. The aqueous layer was further extracted with ethyl acetate (2 x 30 mL). The combined organics were back-extracted with water (2 x 30 mL) and sat. aqueous LiCI (30 mL) and then dried (Na2S04), filtered and concentrated in vacuo to give a dark oil. This was re-dissolved in DCM and directly applied to the top of a 100 g SNAP silica cartridge and purified by SP4 flash column chromatography. The column was eluted with a gradient of 30-70% ethyl acetate in cyclohexane. The appropriate fractions were collected and concentrated in vacuo to afford the product, 6-chloro-N4-(4,4-diethoxybutyl)-N2-methylpyridine-2,4-dicarboxamide (2.39 g, 6.68 mmol, 75 % yield) as a yellow oil. (0904) LCMS (2 min High pH): Rt = 0.92 min, [MH]- = 356.2.

The synthetic route of 6346-09-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; ATKINSON, Stephen John; DEMONT, Emmanuel Hubert; HARRISON, Lee Andrew; LEVERNIER, Etienne; PRESTON, Alexander G; SEAL, Jonathan Thomas; WALL, Ian David; WATSON, Robert J; WOOLVEN, James Michael; (225 pag.)WO2017/174621; (2017); 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. 767-91-9 name is 2′-Methoxyphenyl acetylene, 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. 767-91-9

5b) 2-isopropoxy-5-(2-methoxy-phenylethynyl)-benzoic acid methyl ester 5-lodo-2-isopropoxy-benzoic acid methyl ester (500 mg), 2-methoxy-phenyl acetylene (0.40 ml), palladium dichlorobis(triphenylphosphine) (12 mg) and Cul (6 mg) in diethylamine (10 ml) were stirred at 60C for 12 hours. The reaction mixture was concentrated and extracted with ethylacetate / water. The combined organic layers were dried over sodium sulphate and the solvent was evaporated. The title compound was obtained in 64 % yield after flash chromatography. 1H-NMR (CDCl3): 7.97 d (J = 2.3 Hz, 1 H); 7.59 dd (J = 2.3 Hz / 8.7 Hz, 1 H); 7.47 dd (J = 7.5 Hz / 1.7 Hz, 1 H); 7.30 m (1 H); 6.96 m (3H); 4.62 m (1 H); 3.91 s (3H); 3.88 s (3H); 1.38 d (J = 8.7 Hz, 6H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2′-Methoxyphenyl acetylene, and friends who are interested can also refer to it.

Reference:
Patent; Bayer Schering Pharma Aktiengesellschaft; EP1985612; (2008); 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. 29578-83-4 name is 1-Bromo-3-methoxy-5-methylbenzene, 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. 29578-83-4

Synthesis of 5-(1-(3-methoxy-5-methylphenyl)cyclohexyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (3) A solution of 1-bromo-3-methoxy-5-methylbenzene (2, 8.0 g, 39.80 mmol) in tetrahydrofuran (20 mL) was added dropwise to a flask containing Mg turnings (1.36 g, 55.72 mmol) in tetrahydrofuran (30 mL). Catalytic iodine was added to the mixture and refluxed the reaction for 2 h. To a solution of 5-cyclohexylidene-2,2-dimethyl-1,3-dioxane-4,6-dione (1, 8.0 g, 35.71 mmol) in tetrahydrofuran (50 mL) at 0 C., freshly prepared (3-methoxy-5-methylphenyl)magnesium bromide was added slowly. The reaction was allowed to stir at room temperature for 12 h. On completion, the reaction mixture was quenched with 1 M hydrochloric acid and extracted with ethyl acetate (100 mL). The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 5-(1-(3-methoxy-5-methylphenyl)cyclohexyl)-2,2-dimethyl-1,3-dioxane-4,6-dione as a colorless liquid. Yield: 8.0 g, crude; MS (ESI) m/z 347.12 [M+1]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-3-methoxy-5-methylbenzene, and friends who are interested can also refer to it.

Reference:
Patent; eFFECTOR Therapeutics, Inc.; Sprengeler, Paul A.; Reich, Siegfried H.; Ernst, Justin T.; Webber, Stephen E.; Shaghafi, Mike; Murphy, Douglas; Tran, Chinh; (131 pag.)US10112955; (2018); B2;,
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Adding some certain compound to certain chemical reactions, such as: 3401-47-6, name is 1-Bromo-2-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 3401-47-6. 3401-47-6

2-Methoxynaphthalene-1-thiol (compound 11r) was prepared as follows. (Preparation of (2-methoxynaphthalen-1-yl)magnesium bromide) A THF solution (8 mL) of 1-bromo-2-methoxynaphtalene (4 g, 16.87 mmol) was added, dropwise, to a THF slurry (17 mL) of magnesium turnings (533 g, 21.93 mmol) that had been previously activated through the addition of 1,2-dibromoethane (150 muL, 1.69 mmol). The flask was gently heated with a heat gun, while avoiding boiling. After 30 min, the flask was irradiated at rt in an ultrasonic cleaning bath for 2.5 h to afford a THF solution of the Grignard reagent. Elemental sulfur (0.757 g, 23.62 mmol) was added in one portion, under a N2 blanket, to the 0 C. solution of (2-methoxynaphtalen-1-yl)magnesium bromide (vide supra). After 30 min, lithium aluminum hydride powder (0.32 g, 8.44 mmol) was added in very small portions. After 30 min, the reaction was diluted with cold, aqueous, saturated NH4Cl (20 mL) and then aqueous citric acid 2M (5 mL). The mixture was extracted with dichloromethane (3¡Á30 mL) and, after the removal of volatiles, the resulting slightly yellow solid was partially dissolved with pentane. The pentane solution was cooled by immersion into a -78 C. cooling bath and after 5 min the temperature was raised to 0 C. After 15 min the solution was filtered to afford 3.01 g (94%) of compound 11r as a white crystalline solid: Mp 66-67 C. (lit. 65-68 C.). 1H NMR (400 MHz, Chloroform-d) delta 7.98 (dd, J=8.5, 0.9 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.61 (d, J=9.0 Hz, 1H), 7.49 (ddd, J=8.4, 6.8, 1.3 Hz, 1H), 7.34 (ddd, J=8.0, 6.8, 1.1 Hz, 1H), 7.19 (d, J=8.9 Hz, 1H), 4.39 (s, 1H), 3.95 (s, 3H); 13C NMR (100 MHz, Chloroform-d) delta 151.51, 132.01, 129.28, 128.43, 126.64, 126.28, 124.04, 123.98, 114.72, 112.71, 56.82; IR (ATR) 3052, 2937, 2838, 2579, 1506, 1265, 1247, 1075, 797, 767, 741 cm-1; HRMS calculated for C22H18O2S2 (disulfide) 401.0640. found 401.0648 (M+Na)+

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 1-Bromo-2-methoxynaphthalene.

Reference:
Patent; DUQUESNE UNIVERSITY OF THE HOLY GHOST; FLEMING, FRASER FERGUSSON; Lujan-Montelongo, Jesus Armando; US2015/239833; (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. 103291-07-2, name is 4-Bromo-1-fluoro-2-methoxybenzene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. 103291-07-2

Under a nitrogen atmosphere, 4-fluoro-3-methoxybromobenzene (163 mg) was added dropwise to a THF suspension of magnesium (23 mg) and iodine (catalytic amount). After heating under reflux,After stirring at room temperature for 30 minutes, {(5S) -2-oxo-5- (propan-2-yl) -3- [6- (trifluoromethyl) pyridin-3-yl] imidazolidin-1-yl} acetaldehyde A THF solution of (50 mg) was added dropwise. After stirring at room temperature for 2 hours,A saturated ammonium chloride aqueous solution was added, and the mixture was extracted with chloroform. The organic layer was concentrated under reduced pressure, and the residue was purified by preparative HPLC.DMSO (2 mL) of the obtained product2-iodoxybenzoic acid (27 mg) was added to the solution,Stir overnight at room temperature. After adding water and filtering through Celite,The filtrate was extracted with chloroform. After concentrating the organic layer under reduced pressure,The residue was purified by PTLC (silica gel, hexane / ethyl acetate = 1: 1),The title compound (24 mg) was obtained.

The synthetic route of 103291-07-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Taisho Pharmaceutical Co Ltd; Moriya, Minoru; Yamamoto, Shuji; Abe, Kimiyoshi; Ota, Hiroyuki; Sun, Ziang Min; Wakasugi, Daisuke; Araki, Hiroko; (49 pag.)JP2015/157764; (2015); A;,
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A common compound: 60792-79-2, name is 2,2′-Oxybis(ethylamine) dihydrochloride, 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. 60792-79-2

[0329] In a typical run, sodium hydroxide (400 mg, 10 mmol) was dissolved in MeOH (70 mL) and 2-(2-aminoethoxy)ethanamine dihydrochloride (1.0 g, 5.65 mmol) was added. The resulting reaction mixture was stirred at room temperature for 30 min. A solution containing Boc20 (740 mg, 3.40 mmol) in THF (15 mL) was then added dropwise, at room temperature, over a period of 15 min. The resulting reaction mixture was stirred at room temperature for 18 h. It was then concentrated under reduced pressure. The resulting residue was taken up in CH2C12 (200 mL) and stirred vigorously at room temperature for 4 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to afford tert-butyl 2-(2- aminoethoxy)ethylcarbamate (850 mg, 74%).

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, 60792-79-2, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CATABASIS PHARMACEUTICALS, INC.; BEMIS, Jean E.; VU, Chi B.; MILNE, Jill C.; JIROUSEK, Michael R.; DONOVAN, Joanne; WO2014/107730; (2014); A2;,
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Some common heterocyclic compound, 35896-58-3, name is 1,2,3,4-Tetramethoxy-5-methylbenzene, molecular formula is C11H16O4, 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. 35896-58-3

Compound 3 (0.32 g, 1.5 mmol) was dissolved in acetonitrile (2 mL), and an excess of asolution of K2S2O8 (1.6 g, 6 mmol) in 3mL water was added at 25 C. The reactionmixture was stirred at room temperature for 1 h. The progress of the reaction was monitoredby TLC. After completion of the reaction, the mixture was extracted withdichloromethane (10mL 3). The organic layers were washed with brine until neutrality,then dried over anhydrous Na2SO4 and concentrated in vacuo. The crude productwas purified by a silica-gel column chromatography with petroleum ether and EtOAc(3:1) to give CoQ0, 0.26 g, 96%, red needles, m.p 56-57 C (lit5 57-59 C). IR: (cm1)3590, 3415, 1661, 1603, 1291, 1226, 999. 1H NMR (400 MHz, CDCl3) d 6.44 (q,J1.7 Hz, 1H), 4.02 (s, 3H, OCH3), 4.00 (s, 3H, OCH3), 2.04 (d, J1.6 Hz, 3H,CH3). 13C NMR (101 MHz, CDCl3) d 184.4 (C5O), 184.2(C5O), 145.0, 144.8, 144.0,131.2, 61.2 (OCH3), 61.1 (OCH3), 15.4 (CH3). GC-MS (EI): m/z 182. The spectroscopicdata are in accord with the literature

The chemical industry reduces the impact on the environment during synthesis 1,2,3,4-Tetramethoxy-5-methylbenzene. I believe this compound will play a more active role in future production and life.

Reference:
Article; Qiu, Yong-Fu; Yan, Yi-Yu; Lu, Bin; Tang, Lei; Zhai, Yu-Lin; Chen, Ke-Xin; Wang, Jin; Organic Preparations and Procedures International; vol. 51; 6; (2019); p. 602 – 605;,
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366-99-4, A common compound: 366-99-4, name is 3-Fluoro-4-methoxyaniline, 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.

Example 4; Parallel Synthetic Method B, for Library II Compounds; Fifty mL (13.5 mmol) of the prepared (4,6-dichloro-[1,3,5]triazin-2-yl)-(3-fluoro-4-methoxy-phenyl) amine solution was divided equally (2 mL or 0.54 mmol each) among 25 barcoded, 40 mL scintillation vials. Individual solutions of each R2NHR (where R2 amine indicates Monomer 2 in Table 2, 0.542 mmol) and DIEA (77 mg /104 muL, 0.596 mmol) in 0.5 mL of CH3CN were prepared and added to the correspondingly labeled 40 mL vials. The resulting solutions were shaken on the J-KEM block overnight at room temperature and then placed in a freezer (about -14 ¡ã C.) without purification until the next reaction.; Example 5; Parallel Synthetic Method C, for Library III Compounds; In an oven-dried round bottom flask, a solution of cyanuric chloride (5.0 g, 27.1 mmol) in 1,4-dioxane (40 mL) was cooled to freezing in a CH3CN/dry ice bath. To this frozen solution was added 40 mL of CH3CN, followed by DIEA (3.85 g/5.19 mL, 29.8 mmol). A solution of 3-fluoro-p-anisidine (3.83 g, 27.1 mmol) in 10 mL of CH3CN was then added slowly via syringe. The reaction mixture was stirred at about -20¡ã C. for about 1h and allowed to warm to room temperature over 1 h. The resulting 2-amino-4,6-dichlorotriazine solution was carried to the next step without purification.

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-Fluoro-4-methoxyaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krishna Reddy, Velagala Venkata Rama Murali; Sridevi, Bhatlapenumarthy Sesha; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209881; (2004); A1;,
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101-84-8, The chemical industry reduces the impact on the environment during synthesis 101-84-8, name is Diphenyl oxide, I believe this compound will play a more active role in future production and life.

Example 1; Decabromodiphenyl ether – Simultaneous bromination and milling in a mixed solvent; To a 1 liter round bottomed flask equipped with a mechanical stirrer, a dropping funnel, a thermocouple and a reflux condenser was added 440 g of solvent mixture (DCM 20 %, CBM 40 %, and DBM 40 % w/w) ; bromine, 475 g; AlCl3,4.3 g; and ceramic beads (1.5-3.5 mm diameter), 814 g-A solution of diphenyl oxide (42.5 g, ) in 20 ml of solvent mixture was dropped into the flask during 70 minutes with stirring while keeping the temperature at 7- 13 C . The reaction mixture was refluxed for 4.5 hours, the flask was cooled and 55 ml of water was carefully added to destroy the catalyst. Excess bromine was bleached with sodium bisulfite solution, the aqueous phase was separated and the organic phase was washed with water. The product mixture was passed through a sieve to remove the ceramic beads and the mixture was filtered, washed with water and dried. The product comprised 99.4 % decabromodiphenyl ether and 0.1 % nonabromodiphenyl ether (in the Examples sometimes abbreviated “Deca” and “Nona”, respectively). Particle size 7.1 microns (dg0) .; Example 2 (comparative); Decabromodiphenyl ether – Bromination without milling in a mixed solvent.; The procedure of Experiment 1 was repeated without the ceramic beads present. The product consisted of 94.1 % Deca and 5.8 % Nona. Particle size 98 microns (d90).; Example 3; Decabromodiphenyl ether- increasing the crystal size of milled Deca in a simulated reaction mixture after bromination and destruction of the catalyst.; The product of Example 1, having a particle size of 7.1 microns (dgo) and an assay of 99.4 %, was charged to a 1 liter flask followed by 440 g of solvent mixture (DCM 20 %, CBM 40 %, and DBM 40 %); 4.3 g AlCl3, 50 g of bromine and 50 ml of water to destroy the catalyst. The mixture was refluxed for 5.3 hours, cooled and bleached with bisulfite. The product was filtered, washed with water and dried. The particle size v/as 28.8 microns (dgo), had an assay of 99.7 % and was easily filtered.; Example 7; Decabromodiphenyl ether – Bromination of pre-milled Deca precursor; To a 2 liter jacketed reaction vessel equipped with a mechanical stirrer, a dropping funnel, a thermocouple and a reflux condenser was added 500 g of milled Deca (content 97.3 %, particle size 3.8 microns (d90) ) , 1945 g of solvent mixture, 444 g bromine and 22 g AICI3. The mixture was heated at reflux for 3.5 hours. Water, 260 ml, was added and the excess bromine was bleached with sodium bisulfite solution. To the thick slurry was added 150 ml of water. The mixture was filtered and the dried solid comprised 99.6 % Deca with particle size 38.5 microns (dgo).; Example 8; Decabromodiphenyl ether- Bromination of pre-milled Deca precursor on an industrial scale; A reactor vessel of 16 cubic meters capacity was charged with 7500 liters of solvent consisting of 12.6 % dichloromethane, 32.5 % bromochloromethane and 54.9 % dibromomethane . Aluminum chloride, 150 kg, 8 tons of pre- milled Deca (Deca content 97.9 % with particle size 14 microns (dg0) ) and 1000 kg of bromine were added. The mixture was heated at reflux for 8 hours and was then bleached with 1340 liters of 38 % sodium bisulfite solution. The upper aqueous solution was decanted and the mixture was washed with two 1200 liters portions of water. Sodium hydroxide, 20 %, was added to neutralize the mixture which was then centrifuged. The product was dried and was found to contain 99.3 % Deca with particle size 42 microns (d90).; Example 9; Decabromodiphenyl ethane – Simultaneous bromination and milling in a mixed solvent; To a 1 liter round bottomed flask equipped with a mechanical stirrer, a dropping funnel, a thermocouple and a reflux condenser was added 520 g of solvent mixture (DCM 6 %, CBM 20 %, and DBM 74 % ) ; bromine, 539 g; AlCl3, 9 g; and ceramic beads (1.5-3.5 mm diameter), 840 g.A 55 % solution of diphenyl ethane in DCM (91.1 g, ) was dropped into the flask during 30 minutes with stirring while keeping the temperature at 21-26 0C. The reaction mixture was refluxed for 6.7 hours, and 120 ml of water was carefully added to destroy the catalyst. Bromine was bleached with sodium bisulfite solution, the aqueous phase was separated and the organic phase was washed with water and was neutralized with 20 % NaOH. The product mixture was passed through a sieve to remove the ceramic beads and the mixture was filtered, washed with water and dried. The product comprised 91.4 % decabromodiphenyl ethane and 7.8 % nonabromodiphenyl ethane. Particle size was 6.1 microns (d90).; Example 10 (comparative); Decabromodiphenyl ethane – Bromination without milling in a mixed solvent.; The procedure of Example 9 was repeated without the ceramic beads present. The product comprised 80.6 % decabromodiphenyl ethane and 18.6 % nonabromodiphenyl ethane. Particle size 22 .microns (dgo).

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

Reference:
Patent; BROMINE COMPOUNDS LTD.; WO2008/26215; (2008); A2;,
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Adding a certain compound to certain chemical reactions, such as: 349-55-3, name is 3-Methoxy-5-(trifluoromethyl)aniline, 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 349-55-3, 349-55-3

EXAMPLE 124 4-(3-Methoxy-5-trifluoromethylanilino)-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidine The title compound was prepared from a mixture of 4-chloro-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidine (50 mg, 0.193 mmol) and 3-methoxy-5-trifluoromethylaniline (55 mg, 0.290 mmol) similar to Example 117 and isolated as a yellow solid (27 mg, 34%). 1H NMR (CDCl3): 9.65-9.64 (m, 1H), 8.75-8.70 (m, 2H), 7.46-7.41 (m, 2H), 7.36 (s, 1H), 7.31 (s, 1H), 7.00 (s, 1H), 6.93 (s, 1H), 3.91 (s, 3H).

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-Methoxy-5-(trifluoromethyl)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Cytovia, Inc.; US2003/69239; (2003); A1;,
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