Category: ethers-buliding-blocks

Synthetic Route of 20781-20-8,Some common heterocyclic compound, 20781-20-8, name is (2,4-Dimethoxyphenyl)methanamine, molecular formula is C9H13NO2, 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.

Ethyl bromoacetate (Scheme 28) (10.0 gm, 59.87 mmol) solution in 20.0 mL of anhydrous THF was added dropwise to a solution of (2,4-dimethoxybenzyl)amine (10.0gm, 59.81 mmol) and triethyl amine (6.06 gm, 59.87 mmol) in anhydrous THF (20.0 mL) at 0 C under nitrogen atmosphere. The reaction mixture was warmed to room temperature and stirred overnight. Brine was added 100 mL, and the reaction mixture was extracted with ethyl acetate (2 x 100 mL). Combined extracts were dried over anhydrous MgSO4 and concentrated under reduced pressure. The purification wasperformed using combiFlash chromatography, Gradient: 20:80 to 50:50 v/v Ethylacetate:Hexane. 7.6 gm (yield 50.2 %) of the alkylation product was obtained as a colorless liquid. m/z calculated for C13H19N04 [M+H]: 254; Obtained: 254.1. The ester (7.5 gm, 29.6 mmol) was dissolved in 40.0 mL of methanol. The reaction mixture was cooled and 2N aq. NaOH (88.82 mmol, 44.0 mL) solution was addeddropwise. The reaction mixture was warmed to room temperature and stirred for 2 h. The reaction mixture was diluted with 75.0 mL of water, cooled in ice bath and neutralized down to 5.0 to 4.5 pH using 2N aq. HC1. The excess water was concentrated under reduced pressure and air streamed to obtain white solid powder. The solid was dissolved in 85:15 v/v, DCM:MeOH (100.0 mL) and filtered, the filtrate was evaporated to obtain7.1 gm of carboxylic acid as a white powder (Hygroscopic). m/z calculated for C11H15N04 [M+Na]: 248; Obtained: 248.1.j0448J The above compound (7.0 gm, 31.08 mmol) and 6.14 gm, 31.08 mmol of 5- chloroisatoic anhydride were mixed in 70.0 mL of p-Xylene and refluxed at 140 C temperature for 3 h. The reaction mixture filtered and crude product recrystallized frommethanol. 8.5 gm of 7-chloro-4-[(2,4-dimethoxyphenyl)methyl]-2,3,4,5-tetrahydro -1H-1,4-benzodiazepine-2,5-dione was obtained as a white powder (75.8 % yield). m/z calculated for C18H17C1N204 [M+H]: 361; Obtained: 361.1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route (2,4-Dimethoxyphenyl)methanamine, its application will become more common.

Reference:
Patent; MEKONNEN, Belew; BUTERA, John, A.; HUANG, Jianxing; (400 pag.)WO2016/205739; (2016); A1;,
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Electric Literature of 36805-97-7, 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. 36805-97-7 name is 1,1-Di-tert-butoxy-N,N-dimethylmethanamine, 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.

Compound 2 was prepared according to a similar previously described protocol. 42 To the solution of 4-carboxybenzaldehyde (521?mg, 3.45?mmol) in benzene (6.5?mL) N,N-dimethylformamide di-tert-butyl acetal (2.5?eq, 1760?mg) was added dropwise over a period of 1?h and refluxed. After 2?h the mixture was cooled down to room temperature and water was added (10?mL). The organic layer was collected and concentrated in vacuum. Product was purified chromatographically (silica gel, eluted with Hexane:EtOAc 6:1, v:v). Compound 2 was obtained in 35.4% yield.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1,1-Di-tert-butoxy-N,N-dimethylmethanamine, and friends who are interested can also refer to it.

Reference:
Article; Vahter, Juergen; Viht, Kaido; Uri, Asko; Manoharan, Ganesh babu; Enkvist, Erki; Bioorganic and Medicinal Chemistry; vol. 26; 18; (2018); p. 5062 – 5068;,
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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. 36942-56-0, name is 2-Bromo-4-methoxy-1-methylbenzene, This compound has unique chemical properties. The synthetic route is as follows., Product Details of 36942-56-0

Mg turnings (3 eq., 3.97 g, 163 mmol) were loaded in a two-necked flask, followed by THF (10 ml_) at room temperature. The magnesium was activated by dibromoethane (0.0531 eq., 0.543 g, 0.25 ml_, 2.89 mmol), and then under stirring a solution of 2-bromo-4-methoxy-l-methylbenzene (1 eq., 11 g, 54.5 mmol) in THF (40 ml_) was added dropwise at a rate sufficient to obtain a refluxing solution. After the addition, the light grey solution was stirred for a further 1 h. at 50 C. Then, after cooling to room temperature, the reaction mixture was diluted with THF (50 ml_), and cooled down to 0 C. Then, under vigourous stirring, neat B(OMe)3(3.5 eq ., 19.8 g, 21.6 ml_, 190 mmol) was quickly added in one portion, which caused a white precipitate to appear. After 15 min. of stirring at 0 C, the cooling bath was removed and the reaction mixture was stirred for 1 h. at room temperature. The reaction was then quenched by a 1M HCI solution, and stirred for lh., diluted with Et20, and the phases were separated. The aqueous phase was extracted with an Et20/THF mixture (1 : 1, v/v), and the combined organic phases were dried over Na2S04. The volatile were removed under reduced pressure and the crude off-white solid thus obtained was triturated with /7-pentane under sonication. The crude product is then recrystallized from MeCN (reflux to room temperature to 4-6 C. The titled compound (5-methoxy-2-methylphenyl)boronic acid (7.33 g, 44.2 mmol, 81%) was obtained as a white solid. The title compound as a low solubility in most water-free organic solvents except for THF.400 MHz) : d = 7.07 (d, J = 8.3 Hz, 1H), 7.04 (d, J = 2.8 Hz, 1H), 6.82 (dd, J = 8.3, 2.9 Hz, 1H), 6.14 (s, 2H), 4.87 (s, 2H signal corresponding to the hydrated boronic acid, due the water-contaminated NCCD3), 3.75 (s, 3H), 2.36 (s, 3H) ppm.

According to the analysis of related databases, 36942-56-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; UNIVERSITE DE STRASBOURG; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; DHERBASSY, Quentin; WENCEL-DELORS, Joanna; COLOBERT, Francoise; (46 pag.)WO2019/115597; (2019); A1;,
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These common heterocyclic compound, 24332-20-5, name is 1,1,2-Trimethoxyethane, 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. category: ethers-buliding-blocks

Step A: Preparation of (Z)-3-(dimethylamino)-2-methoxyacrylaldehyde: The reaction was carried out in a 3-neck flask (500 mL) equipped with an internal thermometer. PCl5 (64.4 g, 294 mmol) was added in small portions (~5 g) to a cold (0 C.) solution of 1,1,2-trimethoxyethane (36 g, 294 mmol) while keeping the internal temperature below 30 C. The mixture was heated to 60 C. for 75 minutes and then placed in an ice bath. DMF (66 mL, 852 mmol) was added via a dropping funnel while maintaining the internal temperature below a temperature of 10 C. The mixture was stirred at room temperature for 40 hours, and MeOH (100 mL) was added dropwise via a dropping funnel while keeping the internal temperature below 10 C. The solution was transferred to an addition funnel and was added dropwise to a 30% solution of sodium methoxide (403 mL, 2.17 mol) in MeOH while maintaining the internal temperature below 20 C. The mixture was heated at reflux for 4 hours and then concentrated. The residue was taken up in water (500 mL) and extracted with dichloromethane (500 mL*3). The combined organics were dried, filtered and concentrated to give the desired product (19 g, 25%). MS (APCI-pos) M+1=130.0.

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

Reference:
Patent; Array Biopharma, Inc.; US2010/63066; (2010); A1;,
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Application of 38336-04-8, 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. 38336-04-8 name is 2-(Benzyloxy)-1-ethanamine, 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: Ethyl 2-(4-chloro-3-nitrophenyl)-2-methylpropanoate (3a)(16.15 g, 0.0594 mol), 4 (27.77 g, 0.149 mol), K2CO3 (28.69 g,0.208 mol), KI (0.99 g, 5.94 mmol), TBAB (1.91 g, 5.94 mmol) and150 mL DMSO were added into a round-bottomed flask. The mixturewas heated to 120 C for 24 h then cooling to room temperature.The reaction mixture was diluted with saturated NH4Claqueous solution (250 mL) and extracted with CH2Cl2 (450 mL).The combined organic layer was washed with brine (300 mL), driedover anhydrous sodium sulfate, filtered, and concentrated in vacuo.The residue was purified by silica gel column chromatography (PE:EtOAc = 4:1) to give compound 5a (15.82 g) as yellow oil in 69%yields.

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

Reference:
Article; Chen, Dongxing; Shi, Jinyu; Liu, Jing; Zhang, Xueying; Deng, Xiaoying; Yang, Yanyan; Cui, Shuang; Zhu, Qihua; Gong, Guoqing; Xu, Yungen; Bioorganic and Medicinal Chemistry; vol. 25; 2; (2017); p. 458 – 470;,
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Synthetic Route of 702-24-9, 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. 702-24-9 name is 4-Methoxy-N-methylbenzylamine, 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: A secondary amine (0.34 mol), sodium methoxide (0.35 mol), diethyl ether (600 mL), and methanol (90 mL) were placed into a 1 L three-neck flask equipped with a stirrer, a condenser with a liquid valve, and a gas inlet. A flow of NO was passed at ~20 ¡ãC with vigorous stirring for 10 ?12 h at a rate allowing to maintainan excessive gas pressure within 13 ? 20 Torr. A dense precipitate formed was filtered, washed with diethyl ether, dried first on the filter, then in vacuo using an oil pump to obtain the corresponding sodium salts.

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

Reference:
Article; Smirnov; Gordeev; Nikitin; Pokhvisneva; Ternikova; Luk?yanov; Russian Chemical Bulletin; vol. 64; 11; (2015); p. 2712 – 2717; Izv. Akad. Nauk, Ser. Khim.; 11; (2015); p. 2712 – 2717,6;,
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Application of 6298-96-0,Some common heterocyclic compound, 6298-96-0, name is 1-(4-Methoxyphenyl)ethylamine, molecular formula is C9H13NO, 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.

A mixture of 5-ethoxy-4-chlorothieno[2,3-d]pyrimidine (163 mg, 0.76 mmol) and (S)-1-(4-methoxyphenyl)ethylamine (120 mg, 0.79 mmol) and triethylamine (159 muL, 1.14 mmol) in DMF (2.0 mL) was allowed to react for 5 hours at 50 C. The reaction mixture was filtered through a cotton plug and purified by High Pressure Liquid Chromatography (HPLC) (Gilson system; Phenomenex column: Luna 5mu C18(2), 150¡Á21.20 mm, 5mu micro) with a water/acetonitrile gradient. Appropriate fractions were pooled to provide 125 mg of pale yellow solid.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-(4-Methoxyphenyl)ethylamine, its application will become more common.

Reference:
Patent; Brewster, William Kirkland; Klittich, Carla Jean Rasmussen; Balko, Terry William; Breaux, Nneka Tuere; Erickson, William Randal; Hunter, James Edward; Lowe, Christian Thomas; Ricks, Michael John; Siddall, Thomas Lyman; Yerkes, Carla Nanette; Zhu, Yuanming; US2006/89370; (2006); A1;,
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These common heterocyclic compound, 64115-88-4, name is 1-Bromo-2-(trifluoromethoxy)benzene, 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. Safety of 1-Bromo-2-(trifluoromethoxy)benzene

2.0 g of 1-bromo-2-(trifluoro-methoxy)benzene (8.3 mmol) were dissolved in 30 ml of dichloromethane. At 0-50C, 1.06 g of chlorosulfonic acid (9.13 mmol), dis? solved in 3 ml of dichloromethane, were added dropwise. The reaction mixture was stirred for 30 min at room temperature. Additional 5.5 equivalents of chloro- sulfonic in dichloromethane were added to drive the reaction to completion.Standard work-up was followed and silica gel chromatography with n-heptane- dichloromethane (6:4) as eluent gave 2.19 g of the title compound.1H-NMR (CDCl3, 400 MHz): delta [ppm] 8.3 (d, 1H), 8.05 (dd, 1H), 7.5 (dd, 1H).

The synthetic route of 1-Bromo-2-(trifluoromethoxy)benzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBOTT GMBH & CO. KG; WO2006/40179; (2006); A1;,
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Synthetic Route of 6298-96-0,Some common heterocyclic compound, 6298-96-0, name is 1-(4-Methoxyphenyl)ethylamine, molecular formula is C9H13NO, 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 1 : A solution of (S)-I -(4-methoxyphenyl)ethanamine (3.10 g, 20.5 mmol) in dichloromethane (30 ml) was cooled to -78 C and a solution of boron tribromide (3.88 ml, 41 mmol) in dichloromethane (15 ml) was added dropwise. The reaction mixture was stirred at -78 C for two hours and then at room temperature for 2 h. The solution was then cooled to 0 C and water (15 ml) was added followed by saturated aqueous sodium carbonate to pH 8. The mixture was partially concentrated by rotary evaporation, tetrahydrofuran (50 ml) was then added followed by di-tert- butyl dicarbonate (4.47 g, 20.5 mmol) and the reaction mixture was stirred at room temperature overnight. The water layer was extracted with ethyl acetate (2x 150 ml) and the combined organic layers were washed with brine, dried over sodium sulfate then filtered and concentrated. The residue was purified by silica gel column chromatography using hexanes: ethyl acetate 4:1 to 3:1 as eluent to afford 1,1- dimethylethyl [(l S)-l-(4-hydroxyphenyl)ethyl]carbamate (2.90 g, 60 % yield). 1H NMR (400 MHz, CDCl3): 7.10 (br s, 2H), 6.73 (d, 2H), 6.07 (br s, IH), 4.91 -4.51 (m, 2H), 1.56-1.25 (m, 12H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-(4-Methoxyphenyl)ethylamine, its application will become more common.

Reference:
Patent; EXELIXIS, INC.; WO2009/55077; (2009); A1;,
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Application of 13101-88-7, 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 13101-88-7 as follows.

1.- 2,5-dimethyl-2-(6-methoxynaphthalen-2-yldiazenyl)furan-3(2H)-one To a suspension of 2-amino-6-methoxynaphthalene (2.6 g, 15 mmol) in H2O (40 ml), HCl conc. was added (8 ml), it was cooled in an ice bath and a NaNO2 solution (1.19 g, 17.3 mmol) in H2O (18 ml) was added dropwise shaking the mixture at 0?C during 30 minutes. The previous solution was diluted in H2O (80 ml), 2,5-dimethylfuran-2,3-dihydrofuran-3-one (1.94 g, 17.3 mmol) was added and was left shaking during 2 hrs at room temperature resulting in a yellow precipitate. It was filtered, washed with water and dried. It was thereby obtained 2,5-dimethyl-2-(6-methoxynaphthalen-2-yldiazenyl)furan-3-one (4.22 g, 95 %) in a solid crude form of an ocre-yellow color that was used directly in the following synthesis step. 1H-NMR (300 MHz, CDCl3) delta ppm: 8.35 (s, 1H), 7.85 (d, J=8,8Hz, 1H), 7.75-7.7 (m, 2H), 7.2 (m, 2H), 5.55 (s, 1H), 3.95 (s, 3H), 2.45 (s, 3H), 1.75 (s, 3H).

According to the analysis of related databases, 13101-88-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Laboratorios Del. Dr. Esteve, S.A.; EP2113501; (2009); A1;,
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