Category: ethers-buliding-blocks

Adding a certain compound to certain chemical reactions, such as: 93919-56-3, name is (4-(Trifluoromethoxy)phenyl)methanamine, 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 93919-56-3, name: (4-(Trifluoromethoxy)phenyl)methanamine

General procedure: To a solution of 4 (290mg, 1.02mmol) in DMF (1.5mL), CDI (198mg, 1.23mmol) was added under N2 protection. The resulting reaction was stirred 50C. After 2h, the mixture was cooled to room temperature, and the corresponding benzylamine (1.53mmol) was added. The resulting reaction was stirred 50C under N2 protection overnight. Then the mixture was cooled to room temperature, quenched with 1M hydrochloric acid, diluted with water (50mL), and extracted with CH2Cl2 (60mL×3). The combined organic layer were washed with saturated solution of NaCl (60mL×3), dried over MgSO4, concentrated and purified by flash chromatography eluting with 5-50% ethyl acetate in petroleum ether, to provide the desired products 5a-5d.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (4-(Trifluoromethoxy)phenyl)methanamine, and friends who are interested can also refer to it.

Reference:
Article; Liu, Siming; Jiang, Ying; Yan, Ruohong; Li, Zhonghuang; Wan, Shanhe; Zhang, Tingting; Wu, Xiaoyun; Hou, Ju; Zhu, Zhengguang; Tian, Yuanxin; Zhang, Jiajie; European Journal of Medicinal Chemistry; vol. 179; (2019); p. 358 – 375;,
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Application of 332-48-9, 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. 332-48-9 name is 1-(2-Bromoethoxy)-4-fluorobenzene, 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 suspension of N-Boc- (L)-dopa 67.27 mmol), 2-(4- fluorophenoxy) ethyl bromide (0.95 eq) and potasium bicarbonate (1.1 eq) in DMA (100 mL) was stirred at 65 C overnight. The reacted mixture was diluted with EtOAc (750 mL), washed with water (2×200 mL) and saturated NaHC03 (2×200 mL), brined, dried over Na2S04, concentrated under reduced pressure, and purified by column chromatography on silica gel (60 A, 200-400 Mesh) eluting with 3:7 EtOAc/Hexane to give a clear oil. [00176] The oil was dissolved in a solution of HCl/1,4-dioxane (4.OM, 100 mL), and the mixture was stirred at room temperature for 1 hour before concentrating under reduced pressure to a solid. After dissolving the solid in a minimal amount of acetonitrile (100 mL), the solution was chilled to 4 C, and the resulting white precipitate was collected on a Buchner funnel, washed with diethyl ether (3×50 mL) and dried under high vacuum to afford the title compound as a solid: ¹H NMR (d6-DMSO) : No. 2.92 (m, 2H), 4.14 (m, 2H), 4.21 (t, J = 6.4 Hz, 1H), 4.42 (t, J = 4.4 Hz, 2H), 6.43 (d, J = 7.6 Hz, 1H), 6.59 (s, 1H), 6.60 (d, J = 8.0 Hz, 1H), 6.94 (m, 2H), 7.12 (3, 2H), 8.40 (s, 3H), 8.90 (m, 2H). MS (ESI) m/z 336 (M+H) (at) and 334 (M-H)-.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(2-Bromoethoxy)-4-fluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; XENOPORT, INC.; WO2005/121070; (2005); A1;,
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954235-83-7, name is 1-Bromo-2-(difluoromethoxy)-4-fluorobenzene, 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. Recommanded Product: 954235-83-7

A mixture of l-bromo-2-(difluoromethoxy)-4-fIuorobenzene (intermediate 176a, 70 mg), N-[3- chloro-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl]-2-[4-(ethylsulfonyl)phenyl]acetamide (intermediate 6b, 148 mg), PdCl2(dppi)-CH2CI2 adduct (18.98 mg) and Cs2C03 (114 mg) in acetonitrile (1.5 mL)/water (0.5 mL) was sealed in a vessel and heated in (lie microwave at 100C for 45 mins. The reaction mixture was filtered through celite and silica gel. The filtrate was concentrated under reduced pressure and the residue was purified by MDAP to afford N-(2-chloro-2′- (difluoromethoxy)-4′-fluoro-[l, -biphenyl]-4-yl)-2-(4-(ethylsulfonyl)phenyl)acetamide (22 mg) as a white solid. ?-NMR (400 MHz, DMSO-<¾ delta ppm 1.10 (t, /= 7.2 Hz, 3H), 3.28 (q, J= 7.2 Hz, 2H), 3.84 (s; 2H), 7.21 (t, J= 73.2 Hz, 1H), 7.21 (m, 2H)} 7.28 (d, J - 8.4 Hz, 1H), 7.37 (m, 1H), 7.53 (dd, J= 2.0 Hz, 8.4 Hz, 1H), 7.62 (d, J= 8.0 Hz, 2H), 7.86 (d, J= 8.4 Hz, 2H), 7.91 (d, J= 2.0 Hz, 1H), 10.55 (s, 1H); 19F-NMR (376 MHz, DMSO-rf6) delta ppm -82.43, -110.64; MSiES4) m/? 498 (MH+). The synthetic route of 954235-83-7 has been constantly updated, and we look forward to future research findings. Reference:
Patent; GLAXO GROUP LIMITED; WANG, Yonghui; CAI, Wei; LIU, Qian; MENG, Qinghua; CHENG, Yaobang; YANG, Ting; ZHANG, Guifeng; XIANG, Jianing; WU, Chengde; WO2013/29338; (2013); A1;,
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Electric Literature of 104197-14-0, 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. 104197-14-0 name is 4-Bromo-2,6-difluoroanisole, 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.

Intermediate 112 2-(3,5-difluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxa borolane To a solution of intermediate 111 (2.0 g, 8.968 mmoles) in Dioxan (40 ml), bis(pinacaloto)diboron (2.73 g, 10.76 mmoles) and potassium acetate (2.64 g, 26.90 mmoles) were added and the system is degassed for 30 min Bis(diphenylphosphinoferrocene)dichloro palladium.CH2Cl2 (0.219 g, 0.269 mmoles) was added under nitrogen atmosphere and heated to 80 C. After 12 h, the reaction mixture filtered through celite and concentrated. The crude product was purified by column chromatography with ethyl acetate:petroleum ether to afford the title compound as yellow liquid (2.2 g, 90% yield).). 1H-NMR (delta ppm, DMSO-d6, 400 MHz): delta delta 7.318 (d, J=8.7 Hz, 2H), 4.02 (s, 3H), 1.32 (s, 12H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-2,6-difluoroanisole, and friends who are interested can also refer to it.

Reference:
Patent; Rhizen Pharmaceuticals SA; Incozen Therapeutics Pvt. Ltd.; US2011/118257; (2011); A1;,
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Reference of 111-95-5,Some common heterocyclic compound, 111-95-5, name is Bis(2-methoxyethyl)amine, molecular formula is C6H15NO2, 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.

EXAMPLE 5 Synthesis of DTPA bis(di(2-methoxyethyl-amide)(3) 12.4 ml of bis(2-methoxyethyl)amine (0.084 mol), dissolved in 40 ml of anhydrous DMF, are added dropwise to 5_grams of DTPA anhydride (0.014 mol), dissolved in 80_ml of anhydrous DMF, under argon at 80 C. The reaction medium is kept stirred for 24 hours.After concentrating and addition of diethyl ether, the oily precipitate is separated from the solvents by settling.This residue is dissolved in the minimum amount of CHCl3 and reprecipitated from Et2O. After drying under vacuum, a hygroscopic foam (3) is obtained (6.43 g, yield of 74%), used without additional purification. 1H NMR (D2O+NaOD): 2.50 (t, 4H), 2.52 (t, 4H), 2.98 (s, 2H), 3.11 (s, 4H), 3.31 (s, 6H), 3.32 (s, 6H), 3.51 (s, 4H), 3.53-3.56 (m, 16H).13C NMR (D2O): 45.94, 47.03, 47.81, 49.75, 53.69, 56.29, 57.78, 67.16, 69.56, 69.69 (CH2); 58.63, 59.07 (OCH3); 166.9, 170.5, 175.7 (CO2H and CO). ES-MS: ES-: 622.1 ([M-H]-), ES+: 624.3 ([M+H]+), 646.2 ([M+Na]+).

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

Reference:
Patent; Lemaire, Marc; Foos, Jacques; Guy, Alain; Chitry, Frederic; Pellet-Rostaing, Stephane; Vigneau, Olivier; US2004/81604; (2004); A1;,
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Related Products of 156573-09-0, The chemical industry reduces the impact on the environment during synthesis 156573-09-0, name is 1-Bromo-4-ethoxy-2,3-difluorobenzene, I believe this compound will play a more active role in future production and life.

According to the synthetic scheme shown above, compound (T-2) (129.5 g) obtained as an intermediate of Example 1 was dissolved in DryTHF (500 ml), and the resultant solution was cooled to -70C. In a nitrogen atmosphere, n-BuLi (500 ml) was added dropwise, and agitation was carried out at -70C for 2 hours. Then, a DryTHF solution of trimethyl borate (129.5 g) was slowly added dropwise at -70C, and the resultant solution was heated to room temperature and agitated for 16 hours. After completion of the reaction, 2N-HCl (200 ml) was added, and then extraction was carried out with toluene, an organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then the resultant solution was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and thus a light brown solid was obtained. The resultant material was subjected to recrystallization (heptane: toluene = 4 : 1 in a volume ratio), and thus (T-20) was obtained as a colorless crystal (117.2 g, yield: 71%).

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, 1-Bromo-4-ethoxy-2,3-difluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; JNC Corporation; JNC Petrochemical Corporation; EP2484658; (2012); A1;,
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These common heterocyclic compound, 22236-08-4, name is 3-(Difluoromethoxy)aniline, 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. Quality Control of 3-(Difluoromethoxy)aniline

A solution of 4-chloro-6-nitro-2- (pyrazin-2-yl) quinazoline (1.00 g, crude, 3.7 mmol, 1.0 equiv), 3- (difluoromethoxy) benzenamine 600 mg, 3.7 mmol, 1.0 eq) and Et 3 N (1.00 g, 10 mmol, 3.0 eq) was stirred at 75 C. for 18 h. After cooling, the volatiles were removed in vacuo and the residue was washed with H 2 O (100 mL × 2). The solid was dried in vacuo to give 1.40 g of N- (3- (difluoromethoxy) phenyl) -6-nitro-2- (pyrazin-2-yl) quinazolin-4-amine as a black solid 90.2% at the stage). LCMS m / z = 411.0 (M + 1) (Method A) (retention time = 1.61 min).

The synthetic route of 3-(Difluoromethoxy)aniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; OTSUKA PHARMACEUTICAL COMPANY LIMITED; SUZUKI, MASAKI; KONDO, KAZUMI; KURIMURA, MUNEAKI; VALLURU, KRISHNA REDDY; TAKAHASHI, AKIRA; KURODA, TAKESHI; TAKAHASHI, HARUKA; FUKUSHIMA, TAE; MIYAMURA, SHIN; GHOSH, INDRANATH; DOGRA, ABHISHEK; HARRIMAN, GERALDINE; ELDER, AMY; SHIMIZU, SATOSHI; HODGETTS, KEVIN J; NEWCOM, JASON S; (678 pag.)JP6121658; (2017); B2;,
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These common heterocyclic compound, 6443-69-2, name is 1,2,3-Trimethoxy-5-methylbenzene, 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. Application In Synthesis of 1,2,3-Trimethoxy-5-methylbenzene

Eine Loesung von 1047 g (3,973 mol) 5-Brom-2-methoxy-6-methylben- ZOESaeURECHLORID in 1715 g Chlorbenzol wurden mit 0,72 g (0,0044 mol) (Beispiele 1 bis 4und 7) bzw. 0,36 g (0,0022 mol) (Beispiel 5) bzw. 0,18 g (0,0011 mol) (Beipiel 6) wasserfreiem Eisen- (III) chlorid versetzt und zu einer Loesung von 868,7 g (4,768 mol) 3,4, 5-Trimethoxytoluol in 467,8 g Chlorbenzol bei der in der Tabelle angegebenen Reaktionstemperatur waehrend 4 h dosiert. An- schliessend wurde das Reaktionsgemisch 2 h bei Reaktionstemperatur nachgeruehrt. Zur Entfernung der entstandenen HC1 wurde waehrend der Dosier-und Nachruehrzeit ein konstanter Stickstoffstrom durch das Reaktionsgemisch geleitet (der jeweilige Volumenstrom kann der Tabelle entnommen werden). Anschliessend wurde das Chlorbenzol bei 80 mbar und Temperaturen von 80-105C abdestilliert. Reinheit und Ausbeute der rohen Produktschmelze wurden vor Kristallisation mittels quantitativer HPLC analysiert (Ergebnisse siehe Tabelle). Zur Kristallisation des 5-Bromo-2′, 6-dimethyl-2,4′, 5′, 6′-tetrame- thoxybenzophenons (I’) wurden 4900 g Methanol bei 50C vorgelegt und die 105C heisse Schmelze eingetragen. Die Kristallisation er- folgte durch Abkuehlung mittels einer Temperaturrampe bis AUF-5C. Die Titelverbindung wurde durch Zentrifugation isoliert, auf der Zentrifuge mit Methanol gewaschen und getrocknet.

The synthetic route of 1,2,3-Trimethoxy-5-methylbenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BASF AKTIENGESELLSCHAFT; WO2004/54953; (2004); A1;,
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Reference of 6781-17-5, A common heterocyclic compound, 6781-17-5, name is 2-(2-Ethoxyphenoxy)ethanamine, molecular formula is C10H15NO2, 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.

4.87 g of 2-methoxy-5-(2-oxopropyl)benzenesulfonamide, 3.62 g of 2-(2-ethoxyphenoxy)ethylamine and 10 mg of sodium acetate were added to 30 ml of acetonitrile. The mixture was heated while stirred under reflux for about 1 hour. Then, the solvent was evaporated off in vacuo, to give 7.84 g of an imine compound as a powder. The obtained imine compound was again dissolved in 70 ml of acetonitrile, and to this was added 1.0 g of anhydrous magnesium sulfate. The mixture was cooled to -3 to 3C under argon atmosphere. To this mixture was added the whole amount of the above catalyst-containing mixture, and stirring continued at the same temperature for about 30 minutes. To this was added dropwise 12.0 ml of a mixed solution of formic acid/triethylamine (molar ratio: 5/2), and then stirring further continued at the same temperature for about 5 hours. After that, the reaction mixture was gradually returned to room temperature, and stirring continued overnight for completion of the reaction. After that, the solvent was evaporated off in vacuo and the residue was dissolved in methyl isobutyl ketone. Following this, extraction with aqueous methanesulfonic acid solution was performed. After the aqueous layer was rendered weakly alkaline with aqueous sodium hydroxide solution, separated oily material was extracted with methyl ethyl ketone. The extract solution was washed with saturated brine, dried and concentrated, to give 7.96 g of 5-[2-[(2-(2-ethoxyphenoxy)ethyl)amino]propyl]-2-methoxybenzenesulfonamide (crude crystal containing excess R-isomer) as a light brown powder. The obtained compound was analyzed using a chiral chromatography column (CHIRALPAK AD-H; manufactured by Daicel Chemical Industries, Ltd.) with a solvent made of n-hexane/2-propanol/diethylamine (800/200/1). The result showed that the optical purity of the R-isomer was 70.7%ee. Then, 6.0 g of the crude crystal was dissolved in 42.0 ml of aqueous acetone containing 10% water and to this was added 3.36 g of (R)-mandelic acid. The mixture was heat-dissolved, and then allowed to stand at 15 to 25C overnight. The precipitate was collected by filtration, washed with acetone and dried, to give 4.56 g of (R)-tamuslosin (R)-mandelate, i.e., (R)-5-[2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide (R)-mandelate as a colorless crystal. The optical purity of the R-isomer of the obtained compound was 97.0%ee. Moreover, recrystallization from aqueous acetone containing 10% water was performed to give 3.29 g of a purified product. The optical purity of the R-isomer of the purified product was 100%ee.Optical rotation: [alpha]D20 -31.90 (C = 0.5, MeOH) NMR: 1H-NMR (200MHz, DMSO-d6): delta 0.99-1.03 (3H, d), 1.23-1.30 (3H, t), 2.47-2.59 (1H, q), 2.97-3.05 (1H, q), 3.10-3.30 (1H, m), 3.14-3.20 (2H, t), 3.88 (3H, s), 3.94-4.04 (2H, q), 4.09-4.15 (2H, t), 4.43 (2H, m), 4.75 (1H, s), 6.82-7.43 (9H, m), 7.04 (2H, m), 7.58-7.60 (1H, d)

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; Hamari Chemicals, Ltd.; EP2172443; (2010); A1;,
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Application of 19056-40-7, A common heterocyclic compound, 19056-40-7, name is 4-Bromo-3-methoxyaniline, molecular formula is C7H8BrNO, 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.

To a solution of 4-bromo-3-methoxyaniline (1k) (2.00 g, 9.9 mmol) in water (50 mL) was added hydrochloric acid (4 mL) and sodium nitrite , NaNO2) (0.75 g, 10.9 mmol) is slowly added at 0°C. The mixture was stirred at 0 °C for 30 minutes and then potassium carbonate (1.67 g, 11.9 mmol), copper cyanide (CuCN) (1.06 g, 11.9 mmol) and potassium cyanide (KCN) Mmol) dissolved in water (50 mL). The mixture is stirred at 70°C , cooled, and extracted with toluene. Magnesium sulfate is added to the extracted organic layer to remove water and concentrated under reduced pressure. The concentrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane: ether = 6: 1) , 4-bromo-3-methoxybenzonitrile can be obtained in the form of yellow powder.

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; Konkuk University Industrial Cooperation Corp; Chong, Yu-Hun; Park, Kwang-Su; Kim, Mi-Kyung; Kim, Kyung-Do; (20 pag.)KR2017/17173; (2017); A;,
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