Month: October 2020

103291-07-2, 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. 103291-07-2, name is 4-Bromo-1-fluoro-2-methoxybenzene, A new synthetic method of this compound is introduced below.

To a solution 5-bromo-2-fluoroanisole (109 g, 0.54 mol), ZnF2 (2.52 g, 24.39 mmol), Pd(dba)2 (3.08 g, 5.35 mmol), and P^Bu3 (5.2 mL of a 50% solution in toluene, 11 mmol) in DMF (1 L) was added trimethylsilyl methyl ketene acetal (121 g, 0.7 mol). The reaction mixture was stirred at 80-90 0C for 5 h under nitrogen atmosphere and then was allowed to cool to room temperature and diluted with EtOAc. The reaction mixture was filtered through Celite. The filtrate was washed with H2O (2 L) and the aqueous layer was extracted with EtOAc (2.5 L). The combined extracts were washed with brine (2 L x 2), dried over MgSO4, and concentrated at reduced pressure to give methyl 2-(4-fluoro-3- methoxyphenyl)-2-methylpropanoate (151 g), which was used for the next step without further purification. 1U NMR (400MHz, CDCl3): delta 7.04-6.98 (m, IH), 6.95-6.92 (dd, IH), 6.88-6.85 (m, IH), 3.89 (s, 3H), 3.67 (s, 3H), 1.57 (s, 6H).

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; EXELIXIS, INC.; BOLLU, Venkataiah; BOREN, Brant, Clayton; DALGARD, Jackline, Eve; FLATT, Brenton, T.; HAQ, Nadia; HUDSON, Sarah; MOHAN, Raju; MORRISSEY, Michael; PRATT, Benjamin; WANG, Tie-lin; WO2010/93845; (2010); A1;,
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The chemical industry reduces the impact on the environment during synthesis 588-96-5, name is p-Bromophenetole, I believe this compound will play a more active role in future production and life. 588-96-5

General procedure: In air, aryl halide (0.2 mmol), arylboronic acid (0.22 mmol),K2CO3 (0.3 mmol), 5 ml of distilled water, and 2 mg of catalystwere combined in a 10 ml round bottom flask. The reactionmixture was magnetically stirred and the temperature wasmaintained at 75 C in an oil bath. Reaction progress was monitoredby TLC. After reaction was completed, the reaction mixturewas cooled to room temperature and filtrated. The filtratedsolid was washed with water (35 ml) and dissolved withethyl acetate. The catalyst was separated by filtration, washedwith water, and dried in vacuum. The combined organic phasewas dried with anhydrous MgSO4, and the solvent was removedunder reduced pressure to give the product.

The chemical industry reduces the impact on the environment during synthesis 588-96-5. I believe this compound will play a more active role in future production and life.

Reference:
Article; Ma, Hengchang; Bao, Zhikang; Han, Guobin; Yang, Ningning; Xu, Yufei; Yang, Zengming; Cao, Wei; Ma, Yuan; Cuihua Xuebao/Chinese Journal of Catalysis; vol. 34; 3; (2013); p. 578 – 584;,
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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. 22236-10-8, name is 4-(Difluoromethoxy)aniline, A new synthetic method of this compound is introduced below., 22236-10-8

General procedure: Ethyl 4-bromo-1H-indole-2-carboxylate (1 eq), Pd2(dba)3 (0.1 eq), X-phos(0.2 eq), Cs2CO3 (3 eq) and aryl amine (3 eq) was added to a microwave tube,dissolved in 1,4-dioxane, and filled with argon gas. The microwave reaction wascarried out at 100 C for 0.5-1.5 h, and the starting material disappeared. The mixturewas cooled to room temperature and concentrated. Ethyl acetate was added todissolve the residue, and the mixture was washed with saturated brine and water, driedover anhydrous Na2SO4, and concentrated in vacuo. The crude product was purifiedby column chromatography to afford the target compound. Compounds 8m-8o, 8s,8a-3 ~ 8a-5, 8a-13, 8a-15 ~ 8a-17, 8o-1 ~ 8o-24 were prepared with method 3.

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:
Article; Cui, Guonan; Lai, Fangfang; Wang, Xiaoyu; Chen, Xiaoguang; Xu, Bailing; European Journal of Medicinal Chemistry; vol. 188; (2020);,
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111-95-5, A common heterocyclic compound, 111-95-5, name is Bis(2-methoxyethyl)amine, molecular formula is C6H15NO2, 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.

Example 36; N,N-bis(2-methoxyethyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-8-amine dihydrobromide; (1) tert-butyl 8-[bis(2-methoxyethyl)amino]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate; A solution of tert-butyl 8-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (200 mg, 0.609 mmol), bis(2-methoxyethyl)amine (0.270 ml, 1.83 mmol), X-phos (17.4 mg, 0.0365 mmol), tris(dibenzylideneacetone)dipalladium(0) (11.0 mg, 0.0120 mmol), sodium tert-butoxide (87.5 mg, 0.912 mmol) and dioxane (4 ml) was stirred under an argon atmosphere for 2 hr at 80C. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the desired product (230 mg, 99.1%) as an oil. 1H-NMR (CDCl3) 5; 1.42 (9H, s), 3.34 (6H, s), 3.52 (8H, s), 3.69-3.76 (2H, m), 4.01-4.04 (2H, m), 4.31-4.38 (2H, m), 6.32-6.39 (2H, m), 6.97-6.99 (1H, m)..

The synthetic route of Bis(2-methoxyethyl)amine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2123644; (2009); A1;,
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A common heterocyclic compound, 437-82-1, name is 2,6-Difluoroanisole, molecular formula is C7H6F2O, 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. 437-82-1.

Step 1. Preparation of 3,5-difluoro-4-methoxyacetophenone To a stirred suspension of AlCl3 (24.05 g, 180.40 mmol) in chloroform (300 mL, dried by passage through alumina) at 4 C. (ice bath) under nitrogen was added acetyl chloride (11.0 mL, 152.65 mmol) over 20 minutes. This chilled suspension was stirred at 0 C. for 30 minutes and 2,6-difluoro anisole was added dropwise over 30 minutes. The resulting suspension was warmed to room temperature and stirred overnight. The reaction was quenched by slowly pouring it into a rapidly stirred ice/water mixture. The water layer was extracted with methylene chloride (2*50 mL) and the organic phases were combined and concentrated in vacuo yielding a clear mobile oil. In a 50 mL round bottomed flask was added the above clear oil, DMF (25 mL), K2 CO3 (15 g). Methyl iodide (6 mL) was added and the suspension stirred at 45 C. under nitrogen overnight. water (1 mL) was added and the mixture was heated for an additional 14 hours. The crude reaction mixture was cooled to room temperature, diluted with water (250 mL) and extracted with diethyl ether (3*100 mL). The ether phase was washed with sodium bicarbonate saturated solution, potassium bisulfate (0.1N solution), dried over MgSO4, filtered and concentrated in vacuo yielding a clear mobile liquid. This liquid was distilled (30 C., 1 mm) yielding 12.5 g of a clear liquid which was a mixture of 3,5-difluoro-4-methoxyacetophenone and 3,5-difluoro-4-acetoxyacetophenone in an 85:15 ratio.

The synthetic route of 2,6-Difluoroanisole has been constantly updated, and we look forward to future research findings.

Reference:
Patent; G.D. Searle & Co.; US5756529; (1998); A;,
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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 1484-26-0 as follows. 1484-26-0

A mixtureof triethyl orthoformate (92 mL, 0.55 mol) and 2,2-dimethyl- [1, 3] – dioxane-4,6-dione (75.3 g, 0.522 mol) (Meldrum’s acid) was heated at55 C for 90 minutes and then cooled to45 C. A solution of 3-benzyloxyaniline (100.2 g, 0.5029 mol) in methanol (200 mL) was slowly added to the reaction over a period 45 minutes while maintaining the reaction temperature below50 C. The reaction was then heated at45 C for one hour, allowed to cool to room temperature, and stirred overnight. The reaction mixture was cooled to 1 C, and the product was isolated by filtration and washed with cold ethanol (-400 mL) until the filtrate was colorless.5-{[(3- Benzyloxy) phenylimino]methyl}-2,2-dimethyl- [1, 3] -dioxane-4,6-dione (170.65 g) was isolated as a tan, powdery solid. ‘H NMR (300MHz, DMSO-d6) : 8 11.21 (d, J= 14.2 Hz, 1H), 8. 61 (d, J= 14.2 Hz, 1H), 7.49-7. 30 (m, 7H), 7.12 (dd, J= 8. 1,1. 96 Hz, 1H), 6.91 (dd, J= 8.4, 2.1 Hz, 1H), 5.16 (s, 2H), 1. 68 (s, 6H).

According to the analysis of related databases, 1484-26-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; 3M INNOVATIVE PROPERTIES COMPANY; WO2005/48933; (2005); A2;,
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1535-73-5, 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. 1535-73-5 name is 3-Trifluoromethoxyaniline, 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 a solution of 3-trifluoromethoxy aniline (0.5 g, 2.8 mmol) in CH2Cl2 (70 ml) is added dropwise, phenyl chloroformate (1.06 ml, 8.5 mmol) and pyridine (0.226 ml, 2.8 mmol) at 0 C. The reaction mixture is stirred at 0 C. for 30 min. The solution is washed with 0.1 N HCl, 5% NaHCO3, brine, and concentrated under vacuum. The resulting solid is crystallized from n-heptane to give white needles 0.6 g (71% yield). HRMS (EI) calcd for C14H10F3NO3 297.0613, found 297.0613. Example 405 (from 4-amino-3-methylphenol and phenyl 3-(trifluoromethoxy)phenylcarbamate) is prepared by following Method D, making non-critical modifications. The resulting residue is triturated with CH3CN to give an off white solid 0.07 g (33% yield). HRMS (ESI) calcd for C15H13N2O3F3+H 327.0956, found 327.0954.

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

Reference:
Patent; Piotrowski, David W.; Rogers, Bruce N.; McWhorter JR., William W.; Walker, Daniel Patrick; Corbett, Jeffrey W.; Groppi JR., Vincent E.; Rudmann, Daniel G.; US2003/236287; (2003); A1;,
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929-75-9, Adding a certain compound to certain chemical reactions, such as: 929-75-9, name is 1,11-Diamino-3,6,9-trioxaundecane, 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 929-75-9.

General procedure: A two-neck flask equipped with a magnetic stirrer and a reflux condenser was filled with dry argon and then charged with diazacrown ether 3 or 4 (0.2 mmol), Pd(dba)2 (8-16 mol.%), the phosphine ligand BINAP (9-18 mol.%), and anhydrous dioxane (10 mL). After stirring for 2-3 min, an appropriate amine 5 (0.2 mmol) and ButONa (0.6 mmol) were added. The reaction mixture was refluxed for 24 h. After completion of the reaction, the precipitate that formed was filtered off and washed with CH2Cl2 (10 mL). The combined filtrates were concentrated in vacuo. The residue was dissolved in CH2Cl2 (5 mL) and washed with water (3¡Á10 mL). The organic layer was separated, and the aqueous layers were combined to extract organic matter with CH2Cl2 (3¡Á10 mL). The combined organic fractions were dried over 4 A molecular sieves and concentrated in vacuo. The residual thick dark oil was chromatographed on silica gel using the following sequence of eluents: CH2Cl2, CH2Cl2-MeOH (100 : 1)-(3 : 1), CH2Cl2-MeOH-NH3 (100 : 20 : 1)-(10 : 4 : 1).

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, 1,11-Diamino-3,6,9-trioxaundecane, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Chernichenko; Averin; Buryak; Beletskaya; Russian Chemical Bulletin; vol. 63; 9; (2014); p. 2056 – 2063; Izv. Akad. Nauk, Ser. Khim.; 9; (2014); p. 2056 – 2063,8;,
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These common heterocyclic compound, 54314-84-0, name is ((3-Bromopropoxy)methyl)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. 54314-84-0

Example 25; 5-{(lJ?)-2-[({l-[3-(Benzyloxy)propyl]-4-hydroxypiperidin-4-yl}methyl)amino]-l- hydroxyethyl}-8-hydroxyquinoin-2(lJH)-one; i) l-(3-Benzyloxy-propyl)-piperidin-4-oneA suspension of benzyl 3-bromo-propyl ether (2.29g), 4-piperidinone hydrate hydrochloride (1.69g), potassium carbonate (anhydrous) (3.45g) and potassium iodide (830mg) were stirred in dry DMF (40ml) at 85¡ãC and continued for 24 h. The reaction was poured into water (200 mL plus brine 25 mL) and extracted with EtOAc. The organic extract was evaporated and the residue was chromatographed on silica gel eluting with 4:3 EtOAc/isohexane giving the sub-titled compound as a colourless oil. Yield: 1.8g 1U NMR (300Mz, CDCl3) delta 7.39 – 7.32 (4H, m), 7.31 – 7.25 (IH, m), 4.52 (2H, d), 3.60 – 3.53 (2H, m), 2.79 – 2.70 (4H, m), 2.61 – 2.54 (2H, m), 2.48 – 2.41 (4H, m), 1.89 – 1.80 (2H, m)

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 54314-84-0.

Reference:
Patent; ASTRAZENECA AB; WO2007/102771; (2007); A1;,
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366-99-4, 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 366-99-4 as follows.

To 124 (1.09 g, 3.5 mmol) dissolved in acetone (25 mL) was added 3-fluoro-p-anisidine (0.54 g, 3.5 mmol) in acetone (5 mL) followed by addition of 2.5 N NaOH (1.4 mL, 3.5 mmol) and water (3.5 mL). The reaction mixture was stirred and heated at reflux for 3 hours. The reaction mixture was extracted three times using dichloromethane; the combined organic layers were washed with brine and dried over potassium carbonate. The sample was filtered, concentrated in vacuo, and the resulting solid was dried overnight under vacuum to yield white solid (E15) (1.332 g, 97percent); mp 194¡ã C.; HPLC: Inertsil ODS 3V C18, 40:30:30 v:v:v [KH2PO4 (0.01 M, pH 3.2):CH3OH:CH3CN], 264 nm, Rt 33.2 min, 97.6percent purity; MS (TOF ES+) m/z 396 (35.0); 394 (M+H, 100).

According to the analysis of related databases, 366-99-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Timmer, Richard T.; Alexander, Christopher W.; Pillarisetti, Sivaram; Saxena, Uday; Yeleswarapu, Koteswar Rao; Pal, Manojit; Reddy, Jangalgar Tirupathy; Krishma Reddy, Velagala Venkata Rama Murali; Sesila Sridevi, Bhatlapenumarthy; Kumar, Potlapally Rajender; Reddy, Gaddam Om; US2004/209882; (2004); A1;,
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