Month: May 2021

These common heterocyclic compound, 106658-14-4, name is 4-Methoxybenzene-1,2-diamine hydrochloride, 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. Formula: C7H11ClN2O

Preparation 21 5-Methoxy-2-mercaptobenzimidazole Refer to Chart H (conversion of H-1 to H-2). To a magnetically stirred solution of 4-methoxy-o-phenylenediamine hydrochloride (20.0 g, 0.115 mol) in 400 ml of ethanol-water (4:1) is added 2 molar equivalent of 85% potassium hydroxide solution and 20 ml of carbon disulfide. The contents are warmed in a 75-80 C. oil bath for 2.5 hours and the solvent is removed in vacuo. To the residual thick slurry is added 200 ml of water, the contents heated to boiling, and 95% ethanol is added until a transparent solution is obtained. The solution is filtered, the filtrate is allowed to stand at 25 C. and the resulting cyrstalline solid is collected, and washed with water-ethanol. Drying in vacuo affords 11.0 g of the titled crystals mp 253-254.2 C. Concentration of the mother liquor and silica chromatography (280 g, acetone-methylene chloride, 1:6) gives an additional 3.9 g of product (total 14.9 g, 72% yield).

The synthetic route of 4-Methoxybenzene-1,2-diamine hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Upjohn Company; US5077407; (1991); A;,
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Synthetic Route of 866633-25-2, 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 866633-25-2 as follows.

A solution of isopropylmagnesium bromide (2M solution in tetrahydrofuran) (83 ml, 0.166 mol) was added drop-wise to a stirred solution of 2-(trifluoromethoxy)-5-fluoro- 1 -bromobenzene (Preparation 49, 27.6 g, 0.107 mol) in anhydrous tetrahydrofuran (125 ml) at -1O0C under an atmosphere of nitrogen. The resulting mixture was stirred at room temperature for 2 hours. Tri/sopropyl borate (26.1 g, 0.139 mol) was then added drop-wise at -100C and the resulting mixture was stirred at room temperature for 16 hours. Hydrochloric acid (1 N aqueous solution) (100 ml) was added drop-wise at O0C and the mixture stirred at room temperature for 30 minutes. Ethyl acetate (150 ml) was added and the layers were separated, the aqueous layer was further extracted with ethyl acetate (2 x 150 ml). The organic extracts were combined and concentrated in vacuo. The residue was dissolved in potassium hydroxide (10% aqueous solution) (50 ml) and extracted with diethyl ether (2 x 150 ml). The separated aqueous layer was acidified to pH~4 by addition of hydrochloric acid (1 N aqueous solution) (100 ml) and extracted with ethyl acetate (3 x 150 ml). The combined organic extracts were dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give an off white solid. Purification by preparative HPLC gave the title compound as an off white solid (5.82 g, 24%).1HNMR (cfe-DMSO): 7.23-7.32 (m, 3H), 7.53-7.55 (m, 1 H), 8.36 (br s, 1 H).MS m/z 223 [MH]-

According to the analysis of related databases, 866633-25-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PFIZER LIMITED; WO2008/135826; (2008); A2;,
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Synthetic Route of 106658-14-4, 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. 106658-14-4, name is 4-Methoxybenzene-1,2-diamine hydrochloride belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

a. To a solution of 1,2-diamino-4-methoxybenzene hydrochloride (2 g) in acetonitrile (20 mL) was added dropwise tert-butylnitrite (1.35 mL) at 0 C. After 4 hours at room temperature, the mixture was concentrated under reduced pressure to a solid residue, which was then dissolved in water. The aqueous solution was neutralized with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under reduced pressure to afford 5-methoxy-1H-benzotriazole as an off-white solid (1.2 g, 85%). MS (ES): M/Z [M+H]=150.

The synthetic route of 4-Methoxybenzene-1,2-diamine hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AVENTIS AGRICULTURE; MERIAL LIMITED; Soll, Mark David; Le Hir de Fallois, Loic Patrick; Huber, Scot Kevin; Lee, Hyoung Ik; Wilkinson, Douglas Edward; Jacobs, Robert Toms; US2014/80862; (2014); A1;,
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Reference of 2338-54-7,Some common heterocyclic compound, 2338-54-7, name is 4-Fluoro-3-methylanisole, molecular formula is C8H9FO, 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 l-fluoro-4-methoxy-2-methylbenzene (2.0 g, 14.29 mmol) in CC , NBS (2.55 g, 14.29 mmol) and PI1CO3H (80 mg) were added. The reaction mixture was heated at reflux for 2 h, cooled to room temperature, and the solid was filtered off. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (eluting with PE/EA = 20/1) to give the target compound (3.0 g) as an oil. 1H NMR (CDC13): delta 6.97-6.83 (m, 3H), 4.48 (s, 2H), 3.78 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4-Fluoro-3-methylanisole, its application will become more common.

Reference:
Patent; ARAGON PHARMACEUTICALS, INC.; KAHRAMAN, Mehmet; GOVEK, Steven, P.; NAGASAWA, Johnny, Y.; SMITH, Nicholas, D.; WO2011/156518; (2011); A2;,
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Electric Literature of 121588-79-2, 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. 121588-79-2, name is trans-4-Methoxycyclohexanamine, This compound has unique chemical properties. The synthetic route is as follows.

4-(4-fluoro-3-nitrophenyl)-3,5-dimethylisoxazole (0.609 g, 2.58 mmol) was dissolved in dry THF (20ml) and TEA (1.079 ml, 7.74 mmol). (lr,4r)-4-methoxycyclohexanamine (0.4 g, 3.10 mmol) was added and the reaction warmed to 60C and left to stir at rt for 84h. After cooling to rt the reaction mixture was poured into ice water (100ml), then extracted with ethyl acetate (2 x 100ml). Combined organics were concentrated in vacuo (azeotroping with acetonitrile) to afford the crude 4-(3,5-dimethylisoxazol-4-yl)- N-((lr,4r)-4-methoxycyclohexyl)-2-nitroaniline (1.1 g, 3.12 mmol, >100%), which was used without purification in the next step; Rt 2.40 min (method 1); m/z 346 (M+H)+

The chemical industry reduces the impact on the environment during synthesis trans-4-Methoxycyclohexanamine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; CELLCENTRIC LTD; PEGG, Neil Anthony; ONIONS, Stuart Thomas; TADDEI, David Michel Adrien; SHANNON, Jonathan; PAOLETTA, Silvia; BROWN, Richard James; SMYTH, Don; HARBOTTLE, Gareth; (376 pag.)WO2018/73586; (2018); A1;,
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Adding a certain compound to certain chemical reactions, such as: 954235-78-0, name is 4-Bromo-2-(difluoromethoxy)-1-fluorobenzene, 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 954235-78-0, Recommanded Product: 954235-78-0

A 40-mL vial containing 4-bromo-2-(difluoromethoxy)-1-fluorobenzene (1.00 g, 4.15 mmol) (purchased from Combi-Blocks, Inc.), 1,1′-bis(diphenylphosphino)ferrocene palladium(II)dichloride dichloromethane adduct (0.169 g, 0.207 mmol), bis(pinacolato)diboron (1.159 g, 4.56 mmol), and potassium acetate (1.222 g, 12.45 mmol) was flushed with N2 and subsequently charged with dioxane (4 mL). The slurry was stirred at 90 C. for 3.5 h. After cooling to rt, the reaction was quenched with H2O and extracted thrice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to a black oil. Column chromatography (25 g Snap Ultra column, 0% to 100% EtOAc/hept) afforded 2-(3-(difluoromethoxy)-4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (178 mg, 0.618 mmol, 14.89% yield) as a brown-black oil. m/z (ESI) 289.2 (M+H)+.

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, 4-Bromo-2-(difluoromethoxy)-1-fluorobenzene, other downstream synthetic routes, hurry up and to see.

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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Reference of 104750-60-9, A common heterocyclic compound, 104750-60-9, name is 2-Bromo-1-(methoxymethoxy)-4-methylbenzene, molecular formula is C9H11BrO2, 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.

2-Bromo-1-(methoxymethoxy)-4-methylbenzene (2.3 g, 9.95 mmol) from Example I-122A was dissolved in tetrahydrofuran (39.8 mL), and Q-Phos (1,2,3,4,5-pentaphenyl-1′-(di-tert-butylphosphino)ferrocene) (0.141 g, 0.199 mmol) and bis(dibenzylideneacetone)palladium (0.114 g, 0.199 mmol) were added. The reaction was sparged with nitrogen 10 minutes. A solution of freshly-prepared (1-(methoxycarbonyl)cyclopropyl)zinc(II) bromide (45.2 mL, 19.91 mmol) in tetrahydrofuran was added dropwise. The reaction mixture was stirred at 50 C. for 30 minutes and at 45 C. for 15 hours. The reaction was cooled to ambient temperature and quenched with saturated aqueous ammonium chloride (40 mL). The mixture was diluted with methyl tert-butyl ether. The aqueous layer was extracted once with methyl tert-butyl ether. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by flash column chromatography, eluting with 0-20% ethyl acetate/heptanes to provide the title compound. 1H NMR (501 MHz, chloroform-d) delta ppm 7.06-6.99 (m, 2H), 6.97 (d, J=8.1 Hz, 1H), 5.16 (s, 2H), 3.60 (s, 3H), 3.45 (s, 3H), 2.28 (s, 3H), 1.63-1.57 (m, 2H), 1.12 (q, J=4.1 Hz, 2H)+

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; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Couty, Sylvain; Desroy, Nicolas; Gfesser, Gregory A.; Housseman, Christopher Gaetan; Kym, Philip R.; Liu, Bo; Mai, Thi Thu Trang; Malagu, Karine Fabienne; Merayo Merayo, Nuria; Picolet, Olivier Laurent; Pizzonero, Mathieu Rafael; Searle, Xenia B.; Van der Plas, Steven Emiel; Wang, Xueqing; Yeung, Ming C.; (189 pag.)US2019/77784; (2019); A1;,
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Adding a certain compound to certain chemical reactions, such as: 6052-10-4, name is 4,4′-(Ethane-1,2-diylbis(oxy))dianiline, 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 6052-10-4, Recommanded Product: 6052-10-4

The TGAE was synthesized (Fig. 1.) according to the reported procedure [23]. A 250-mL two-neck round bottom flask, equipped with magnetic stirrer, thermometer and condenser was charged with 4-(2-(4-aminophenoxy)ethoxy)benzenamine ethane (5.0 g, 0.02 mol), 40 mLtoluene and 1.5 mL 50% manganese nitrate aqueous solution. The reaction mixture was stirred at 333 K for 50 min, and epichlorohydrin (9.63 mL, 0.12 mol) was added slowly. The reaction mixture was kept at 353 K for1 h; then 50% aqueous tetramethylammonium chloride (TMAC, 0.25 g, 0.00, 228 mol) and 3.65 g (0.091 mol) sodium hydroxide were added slowly in portions within 10 min. After addition, the temperature was maintained at 348-353 K and 12 mL distilled water was added, stirred and heated to separate out organic layers, which was washed with brine, separated and concentrated to get TGAE as a viscous brown liquid. 4-(2-(4-(bis(oxiran-2-ylmethyl)amino)phenoxy)ethoxy)-N,Nbis(oxiran-2-ylmethyl) benzenamine TGAE Colour, dark brown viscous liquid, EEW 170.8 g eq-1, Yield, 80%. FTIR (upsilon cm-1): 905 (C-O-C epoxide, asym), 810 (C-O-C epoxide, sym), 1223, 1067 (C-O, alkyl phenyl alcohol), 1375 (C-N ter. amine), 1507, 1456 (C=C aromatic), 2918 (C-H aliphatic), 1H NMR (300 MHz, CDCl3-d3): delta(ppm) = 2.8 (4H, m, 1a), 2.6 (4H, m, 1b), 3.2 (4H, m, 2), 3.7 (4H, m, 3a), 3.4 (4H, m, 3b), 6.8 (4H, dd, J = 9.3, 3.0 Hz, 4), 6.9 (4H, dd, J = 9.3, 2.4 Hz, 5) and 4.25 (4H, s,8). 13C NMR (300 MHz, CDCl3-d3): delta(ppm) = 45.37 (1), 47.18 (2), 50.74 (3), 114.8 (4), 116.4 (5), 151.3 (6), 143.4(7) and 67.4 (8).

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

Reference:
Article; Siddiqi, Humaira Masood; Siraj, Amna; Khalid, Naila; Akhtar, Zareen; Zia Ul Haq, Muhammad; Journal of Thermal Analysis and Calorimetry; vol. 132; 1; (2018); p. 205 – 214;,
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Related Products of 6850-60-8,Some common heterocyclic compound, 6850-60-8, name is (4-Ethoxyphenyl)methanamine, 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.

Synthesis of 5-Bromo-N- (4-ethoxybenzyl) -3-nitropyridin-2-amine (compound 62-2)[0000214] To a stirred solution of 2,5-dibromo-3- nitropyridine (1 g, 3.5 mmol, 1 equiv) in ethanol (10 mL) was added a (4-ethoxyphenyl)methanamine (580 IlL, 3.9 mmol, 1.1 equiv) and triethylamine (1 mL, 7.1 mmol, 2 equiv) . The reaction mixture was allowed to stir at room temperature for 18 hours, at which time LC-MS indicated the reaction was complete. The suspension was filtered and the solid washed with ethanol (2 x 5 mL) to produce compound 62-2 as a yellow solid (1.1 g, 92% yield)

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

Reference:
Patent; SIGA TECHNOLOGIES, INC.; DAI, Dongcheng; BURGESON, James, R.; AMBERG, Sean, M.; HRUBY, Dennis, E.; WO2013/123215; (2013); A2;,
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Application of 4457-67-4, 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 4457-67-4 as follows.

b) 2-(4-Methoxybutoxy)-benzoic acid ethyl ester A solution of 4-methoxybutyl bromide (4.5 g) in acetonitrile (15 ml) is added dropwise under reflux to a mixture of salicylic acid ethyl ester (2.63 ml), powdered potassium carbonate (3.10 g) and potassium iodide (10 mg) in acetonitrile (50 ml), and the reaction mixture is then stirred overnight. After cooling, filtration is carried out, the filtrate is concentrated and the residue is added under a high vacuum. The title compound (4.4 g), Rf (C)=0.28, is obtained in the form of a pale-yellow oil.

According to the analysis of related databases, 4457-67-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Ciba-Geigy Corporation; US5641778; (1997); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem