Month: September 2021

78531-29-0, name is 1,3-Dimethoxypropan-2-amine, 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. Quality Control of 1,3-Dimethoxypropan-2-amine

General procedure: Example 6B (0.018 g, 0.05 mmol) was dissolved in acetonitrile (0.5 ml), and treated with potassium carbonate (0.021 g, 0.15 mmol) and 1 -(2-chloroethyl)pyrrolidine (0.017 g, 0.1 mmol). The reaction mixture was heated via microwave at 180 C for 30 minutes, concentrated in vacuo, and submitted to reverse-phase HPLC (as described in Example 6C) to provide the title compound.

The synthetic route of 78531-29-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBVIE INC.; SWEIS, Ramzi F.; CURTIN, Michael L.; PLIUSHCHEV, Marina A.; HANSEN, Todd M.; LONGENECKER, Kenton; WO2013/170118; (2013); A1;,
Ether – Wikipedia,
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Synthetic Route of 2734-70-5, 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. 2734-70-5 name is 2,6-Dimethoxyaniline, 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.

To an ice-cooled solution of 2,6-dimethoxyaniline (Amfinecom Inc., 2.0 g, 13.1 mmol) in DCM (65 mL) was added N,N-diisopropylethylamine (6.8 mL, 39.2 mmol) followed by cyclobutanecarbonyl chloride (Sigma-Aldrich, 1.56 mL, 13.7 mmol) slowly via syringe. The resulting solution was warmed to RT and stirred for 48 h, then was partitioned between water and DCM (2X). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to provide Example 1.01 (2.92 g, 95percent yield

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

Reference:
Patent; AMGEN INC.; CHEN, Yinhong; DRANSFIELD, Paul John; HARVEY, James S.; HEATH, Julie Anne; HOUZE, Jonathan; KHAKOO, Aarif Yusuf; KOPECKY, David J.; LAI, Su-Jen; MA, Zhihua; NISHIMURA, Nobuko; PATTAROPONG, Vatee; SWAMINATH, Gayathri; YEH, Wen-Chen; RAMSDEN, Philip Dean; (434 pag.)WO2018/93577; (2018); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Related Products of 35822-58-3, 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 35822-58-3 as follows.

General procedure: One equiv. of protected hydrazine was dissolved/suspended in EtOH containing 10% water (approx. 5 ml per 1 mmol of protected hydrazine), 1.05 eq of benzaldehyde acetal was added, followed by the addition of 0.05 equiv. of TsOH in an ethanolic solution (10 mg of TsOH per 0.5 ml of EtOH). The obtained reaction mixture was refluxed and monitored by TLC (silica gel) until full conversion of the starting material was observed. Ethyl acetate/light petroleum mixtures or pure ethyl acetate were used as TLC eluents. After completion of the reaction the solvent was removed under reduced pressure, approx. 15 ml of toluene was added to the residue and the solvent was again removed under reduced pressure. The obtained crude hydrazone was dissolved in commercial stabilized THF (approx. 4 ml per 1mmol of hydrazone), the flask was flushed with argon and 3 equiv. of 1M BH3-THF complex was added at room temperature, followed by 3 hours of stirring. The progress of the reaction was checked by TLC and if some unreacted hydrazone was left, stirring was continued for an additional 45 min. After thefull conversion of hydrazone EtOH (10 ml) was added to the reaction mixture (Caution: Liberation of hydrogen) and the obtained mixture was refluxed for 1 hour. After cooling to room temperature the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with saturated NaHCO3 solution, water and saturated NaCl solution. The aqueous phase was extracted twice with ethyl acetate, the extracts were washed with saturated NaCl solution, combined with the organic phase, dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel by using ethyl acetate/light petroleum 1:1 or 1:2 mixtures or pure ethyl acetate as eluent. For the exact information about the eluent used for monitoring reaction progress and chromatographic purifications, see the Rf value for each compound.

According to the analysis of related databases, 35822-58-3, the application of this compound in the production field has become more and more popular.

Reference:
Article; Mastitski, Anton; Niinepuu, Siret; Haljasorg, Toiv; Jaerv, Jaak; Organic Preparations and Procedures International; vol. 50; 4; (2018); p. 416 – 423;,
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Ether | (C2H5)2O – PubChem

Some common heterocyclic compound, 22094-18-4, name is 1,3-Dibromo-2,2-dimethoxypropane, molecular formula is C5H10Br2O2, 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. name: 1,3-Dibromo-2,2-dimethoxypropane

To a suspension of NaH (4.1 g, 100 mmol) (60% in mineral oil) in DMF (100 mL) was added 2-(4-bromophenyl)acetonitrile (10 g, 51 mmol) followed by l,3-dibromo-2,2-dimethoxypropane (11 g, 42 mmol). The reaction mixture was heated to 60 C for 12 h. After 12 h the reaction mixture was diluted with water (1000 mL) and washed with EtOAc (400 mLx2). The combined organics were washed with brine (100 mL), dried over anhydrous Na2SC>4, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica (petroleum ether : EtOAc = 50: 1 to 20: 1) to afford 1-(4-bromophenyl)-3,3-dimethoxycyclobutanecarbonitrile. MS (ESI) Calc’d [M+H]+, 296; found, 296.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 22094-18-4, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MCGOWAN, Meredeth Ann; ACHAB, Abdelghani; FRADERA, Xavier; HAN, Yongxin; LI, Derun; LIM, Jongwon; LIU, Kun; SCIAMMETTA, Nunzio; WHITE, Catherine, M.; YU, Wensheng; ZHANG, Hongjun; ZHOU, Hua; (109 pag.)WO2019/74747; (2019); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 592-55-2, 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. 592-55-2, name is 1-Bromo-2-ethoxyethane belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

(A) A mixture of 4-bromo-3-methylphenol (10 g, 53.47 mmol), 1-bromo-2-ethoxyethane (10.62 g, 69.40 mmol) and K2CO3 (11.13 g, 79.95 mmol) in DMF (100 mL) was stirred overnight at 75 C. After cooling to rt, brine (250 mL) was added and the mixture was extracted with EtOAc (4*100 mL). The combined organic extracts were washed with brine (4*100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification of the resultant residue by silica gel chromatography (5% EtOAc/petroleum ether afforded 1-bromo-4-(2-ethoxyethoxy)-2-methylbenzene (12.25 g, 88%) as light yellow oil which was used directly.

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

Reference:
Patent; Janssen Pharmaceutica NV; Liang, Yin; Demarest, Keith T.; (109 pag.)US2017/290800; (2017); A1;,
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. 767-91-9, name is 2′-Methoxyphenyl acetylene, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C9H8O

Methyl 4-hydroxy-3-iodobenzoate (0.111 g, 0.40 mmol, 2′-methoxyphenyl acetylene (0.052 ml, 0.40 mmol) 1,1,3,3-tetramethylguanidine (0.502 mL, 4.00 mmol) bis(triphenylphosphine)palladium(II)chloride (0.028 g, 0.04 mmol) and copper(I) iodide (1.36 muL, 0.04 mmol) were dissolved in N,N-dimethylformamide (5 mL). The reaction mixture was heated at 50 C. under an atmosphere of argon over night and the solvent was evaporated. Purification by column chromatography, using heptane/ethyl acetate (9:1) as the eluent gave 0.064 g (57% yield) of the title compound.1H NMR (400 MHz, CDCl3), delta ppm 8.34 (d, 1H), 8.07 (dd, 1H), 8.01 (dd, 1H), 7.53 (d, 1H), 7.40 (s, 1H), 7.33-7.39 (m, 1H), 7.06-7.14 (m, 1H), 7.02 (d, 1H), 4.01 (s, 3H), 3.96 (s, 3H).

According to the analysis of related databases, 767-91-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AstraZeneca AB; US2009/131468; (2009); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 592-55-2, name is 1-Bromo-2-ethoxyethane, 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 592-55-2, COA of Formula: C4H9BrO

A. 2-Ethoxyethoxynitrobenzene 2-Nitrophenol (91.0 g. 0.65 mole), 2-bromoethyl ethyl ether (100.0 g. 0.65 mole), anhydrous potassium carbonate (9.0 g, 0.72 mole) and acetone (1 liter) were refluxed for 65 hours. The reaction mixture was filtered, and the acetone removed by rotary evaporation. The residue was partitioned between 200 ml. of dichloromethane and 100 ml water. The organic phase was further washed with 200 ml. of 10% sodium hydroxide followed by 100 cc of water. The product (58.0 g) was obtained in 42% yield by a vacuum distillation (100-120 C./0.5 mm).

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

Reference:
Patent; GAF Corporation; US4178168; (1979); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Electric Literature of 36942-56-0,Some common heterocyclic compound, 36942-56-0, name is 2-Bromo-4-methoxy-1-methylbenzene, molecular formula is C8H9BrO, 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 RBF was charged with (1,5-cyclooctadiene)(methoxy)-iridium(i) dimer (0.049 g, 0.075 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (0.040 g, 0.149 mmol), and bis(pinacolato)diboron (1.339 g, 5.27 mmol). The flask was flushed with Ar (g), then hexane (15.30 ml) was added. A reflux condenser was attached to the flask, and the flask was heated to 50 C. for 10 minutes. 2-bromo-4-methoxy-1-methylbenzene (2.0 g, 9.95 mmol) was added and the reaction was stirred overnight at 50 C. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 80 g, gradient elution 0-50% EtOAc:Heptane) to afford 2-(4-bromo-2-methoxy-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.694 g, 2.122 mmol, 21.33% yield) as an off-white oily solid. m/z (ESI) 329.1 (M+H)+.

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-4-methoxy-1-methylbenzene, its application will become more common.

Reference:
Patent; Amgen Inc.; Weiss, Matthew; Boezio, Alessandro; Boezio, Christiane; Butler, John R.; Chu-Moyer, Margaret Yuhua; Dimauro, Erin F.; Dineen, Thomas; Graceffa, Russell; Guzman-Perez, Angel; Huang, Hongbing; Kreiman, Charles; La, Daniel; Marx, Isaac E.; Milgrim, Benjamin Charles; Nguyen, Hanh Nho; Peterson, Emily; Romero, Karina; Sparling, Brian; US9212182; (2015); B2;,
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Ether | (C2H5)2O – PubChem

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 27060-75-9, name is 1-Bromo-4-methoxy-2-methylbenzene, A new synthetic method of this compound is introduced below., HPLC of Formula: C8H9BrO

In a four-necked flask equipped with a thermometer, reflux condenser, stirrer, and nitrogen introduction tube,Add 200g of N-methylpyrrolidone and 15.0g (0.11mol) of acetanilide, stir to dissolve acetanilide in N-methylpyrrolidonein.Add 22g (0.12mol) of 30wt% sodium methoxide and gradually heat to 100 C to distill off methanol to prepare acetanilide sodium salt solution.Add 20.2 g (0.1 mol) 4-bromo-3-methylanisole to the reaction bottle at 20 C for 30 minutes,Control the temperature of the material ? 40 , after the addition is complete, continue to stir the reaction at 40 for 45 minutes.15g of methanol was added, and the temperature was raised to 100 C within 30 minutes, and the low-boiling fraction was distilled off. Then, the reaction was continued at 100 C for 30 minutes.Finally, under vacuum conditions, the temperature is controlled within the range of 110-130 C, and N-methylpyrrolidone is distilled off,A reaction mixture containing the target product 4-methoxy-2-methyldiphenylamine was obtained. Add 200 g of water to the reaction mixture containing 4-methoxy-2-methyldiphenylamine and stir well,Dissolve soluble materials and filter to obtain crude 4-methoxy-2-methyldiphenylamine.The crude 4-methoxy-2-methyldiphenylamine is post-treated by methanol recrystallization, centrifugal separation, drying, etc.Obtained target product 4-methoxy-2-methyldiphenylamine 20.5g, purity 99.3%(Gas chromatography analysis),The reaction yield was 95.3% (based on 4-bromo-3-methylanisole).

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; Shandong Dao Ke Chemical Co., Ltd.; Shandong Morui Technology Co., Ltd.; Li Mingxin; Lu Fengyang; Wang Jiahui; Yang Shuren; Li Mingjing; Yan Xue; (13 pag.)CN104628585; (2016); B;,
Ether – Wikipedia,
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Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 3616-56-6, name is 2,2-Diethoxy-N,N-dimethylethanamine, A new synthetic method of this compound is introduced below., Quality Control of 2,2-Diethoxy-N,N-dimethylethanamine

Example 2 (E)-4-Dimethylamino-But-2-Enoic acid-[4-(3-Chloro-4-Fluoro-Phenylamino)-7-((S)-Tetrahydrofuran-3-Yloxy)-Quinazolin-6yl]-Amide 5.6 litres of 30percent hydrochloric acid (53.17 mol) are added to 4.4 litres of water. Then 4.28 kg of 95percent (dimethylamino)-acetaldehyde-diethylacetal (26.59 mol) are added dropwise within 20 minutes at 30° C. The reaction solution is stirred for 8 hours at 35° C. stirred, cooled to 5° C. and stored under argon. This solution is referred to as solution B. 4.55 kg (68.06 mol) of potassium hydroxide are dissolved in 23.5 litres of water and cooled to -5° C. This solution is referred to as solution C. 5.88 kg (10.63 mol) of diethyl ((4-(3-chloro-4-fluoro-phenylamino)-7-(tetrahydrofuran-3-yloxy)-quinazoline-6-ylcarbamoyl)-methyl)-phosphonate and 0.45 kg of lithium chloride (10.63 mol) are placed in 23.5 litres of tetrahydrofuran and cooled to -7° C. The cold solution C is added within 10 minutes. Then solution B is added at -7° C. within 1 hour. After stirring for a further hour at -5° C. the reaction mixture is heated to 30° C. and combined with 15 litres of water. After cooling to 3° C. the suspension is suction filtered, the precipitate is washed with water and dried. Yield: 5.21 kg of crude product, 100percent, water content: 6.7percent The crystallisation of the crude product is carried out with butyl acetate/methylcyclohexane Yield: 78percent purity HPLC 99.4Fl percent, water content 5.4percent

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; Boehringer Ingelheim International GmbH; US2005/85495; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem