Category: 437-82-1

Synthetic Route of 437-82-1, 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.

5 g (34.7 mmol) of 2,6-difluoroanisole and 2.62 g (40 mmol) of cyclopropylnitrile are added in 100 ml of toluene. At room temperature, 77 ml of a 0.5 M solution of KHMDS in toluene is added in drops. The reaction mixture is heated slightly. After stirring overnight at room temperature, water and ethyl acetate are added. It is shaken with 10% sulfuric acid, and the organic phase is separated. After repeated shaking of the aqueous phase with ethyl acetate, the combined organic extracts are washed with brine. After drying on sodium sulfate, it is filtered off, and the solvent is spun off. After chromatography on silica gel (mobile solvent: ethyl acetate/hexane), 2.53 g (38.2%) of the desired compound is obtained.

The synthetic route of 437-82-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Schmees, Norbert; Lehmann, Manfred; Rehwinkel, Hartmut; Strehike, Peter; Jaroch, Stefan; Schaecke, Heike; Schottelius, Amdt J.G.; US2004/209875; (2004); A1;,
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Application of 437-82-1,Some common heterocyclic compound, 437-82-1, name is 2,6-Difluoroanisole, molecular formula is C7H6F2O, 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.

The 2,6-difluoroanisole (4.00 ml, 33 . 9mmol) and sodium iodide (15.0g, 100mmol) dissolved in acetonitrile (50 ml) , trimethylchlorosilane (8.80 ml, 102mmol) is also added and heated to 100 C for 5 hours. Cooling to room temperature, reducing pressure and evaporating solvent, adding water (40 ml), dichloromethane is used for (30 ml × 3) extraction. Combined with the phase, with water (40 ml), saturated salt water (40 ml) washing, dry anhydrous sodium sulfate. Filtering, evaporating solvent under reduced pressure, the crude product purification column chromatography (petroleum ether/ethyl acetate (v/v)=6/1), to get the yellow oil (2.2g, 50%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,6-Difluoroanisole, its application will become more common.

Reference:
Patent; Guangdong East Sunshine Pharmaceutical Co., Ltd.; Zhuo, Yinglin; Wang, Xiaojun; Zhang, Yingjun; Wen, Liang; Wu, Shoutao; Yuan, Xiaofeng; (87 pag.)CN105384687; (2016); A;,
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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. 437-82-1, name is 2,6-Difluoroanisole belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Quality Control of 2,6-Difluoroanisole

500 ml dry reaction flask, replaced with nitrogen gas, was added the compound (IV) 28.8 g of 100 ml of anhydrous 2-methyltetrahydrofuran, in the system under a nitrogen atmosphere, stirred and cooled to -78C, and slowly added dropwise 1.6M n-hexane solution of n-butyllithium in 185 ml. after completion of the dropwise addition, at -60 ~ -50C reaction was stirred for 2 hours.System cooling to -78C, carbon dioxide gas through for 5 hours after completion through ~ -40 -30C was stirred for 3 hours.The reaction system was allowed to warm to room temperature, 200 ml of water, stirred, and the organic solvent is recovered by distillation under reduced pressure, and the residue with 36% hydrochloric acid, filtered, and the filter cake washed with 100 ml of water, dried to give compound (V) 31.6 g.

The synthetic route of 437-82-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ZHEJIANG ZHONGXIN FU CAI CO LTD/ ZHEJIANG ZHONGXIN CHEMICALS CO., LTD.; YUAN, QILIANG; ZHANG, JIABING; XU, PENGFEI; JIANG, XIANBO; CHEN, YINHAO; WANG, CHAO; (16 pag.)CN103819401; (2016); B;,
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Some common heterocyclic compound, 437-82-1, name is 2,6-Difluoroanisole, molecular formula is C7H6F2O, 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. Recommanded Product: 437-82-1

Example 37This example illustrates the preparation of compound 101a according to the approach provided in Scheme 31. The general method is applicable to other compounds of the present invention. In this example, Rv is H and Rw is CD3. Scheme 31Preparation of (5-bromo-2-chlorophenyl)(3,5-difluoro-4-hydroxyphenyl)- methanone (96)To a solution of 5-bromo-2-chlorobenzoic acid (3.2 g, 13.5 mmol) in dichloromethane (40 mL), oxalyl dichloride (1.7 mL, 27.1 mmol) was added. Then N, N-dimethylformamide (50 muL) was added dropwise. After the vigorous evolution of gas ceased, the mixture was stirred at 250C overnight prior to removal of the volatiles under reduced pressure. The residue was dissolved in dichloromethane (20 mL) and cooled to 0 C. Aluminum trichloride (2.7 g, 20.4 mmol) was added in portions, and the mixture was stirred for 10 minutes. Then l,3-difluoro-2- methoxybenzene (2.0 g, 13.8 mmol) was added, and the mixture was stirred at 0 0C for 2 hours. Then the reaction was allowed to warm to 25 C overnight. The reaction was quenched with ice-water (30 mL) and extracted with dichloromethane (2 x 20 mL). The combined organic layers were washed with sodium hydroxide (2 M), water, hydrochloric acid (10%), and brine prior to drying over sodium sulfate. Crude product was obtained after dichloromethane was removed under reduced pressure. The sample was dissolved in tetrahydrofuran/methanol/water (30 mL, v/v/v = 2:3:1), and lithium hydroxide monohydrate (700 mg) was added. The mixture was stirred for 1 hour at 25 0C. The solvent was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (3 x 30 mL), and the extracts were washed with brine, dried over sodium sulfate, and concentrated to a crude product under reduced pressure. The residue was purified by silica column chromatography to give 1.46 g of white solid (30% yield, purity: 95%). 1H-NMR (CDCl3, 400 MHz): delta 7.59-7.62 (m, IH), 7.49-7.50 (m, IH), 7.36-7.42 (m, 3H); HPLC-MS method: Method 2, retention time 3.81 min; MS ES” (m/z): 345(M – I)”.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 437-82-1, its application will become more common.

Reference:
Patent; THERACOS, INC.; SEED, Brian; LV, Binhua; ROBERGE, Jacques, Y.; CHEN, Yuanwei; PENG, Kun; DONG, Jiajia; XU, Baihua; DU, Jiyan; ZHANG, Lili; TANG, Xinxing; XU, Ge; FENG, Yan; XU, Min; WO2010/9243; (2010); A1;,
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Electric Literature of 437-82-1, 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.

A mixture of 1,3-difluoro-2-methoxybenzene (2.5 g, 17.3 mmol) and ethyl succinyl chloride (4.29 g, 26 mmol) in 1,2-dichloroethane (25 mL) was cooled to 0 C. Aluminum chloride (8 g, 60.1 mmol) was added slowly at 0 C. then stirred at rt for 2 h and quenched with ice and aqueous 2N HCl at 0 C. The aqueous layer was extracted twice with methylene chloride and the combined organics were washed with brine, dried (Na2SO4), filtered, and concentrated to provide a crude product. The crude product was purified by ISCO (80 g silica gel column) chromatography using 8.5% EtOAc in hexane to furnish 4-(3,5-difluoro-4-methoxyphenyl)-4-oxo-butyric acid ethyl ester (2.9 g, 61%),

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; Cephalon, Inc.; US2008/27041; (2008); A1;,
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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 437-82-1 as follows. 437-82-1

26 g (180 mmol) of 2,6-difluoroanisole and 14.6 ml (198 mmol) of cyclopropyl cyanide in 500 ml of toluene are admixed dropwise at 0 C. over 40 min with 396 ml of a 0.5 molar (198 mmol) solution of bis(trimethylsilyl)potassium amide in toluene. The mixture is stirred at room temperature for 18 hours and admixed with water and 1M sulphuric acid, with ice cooling. The organic phase is separated off and the aqueous phase is extracted repeatedly with ethyl acetate. The extracts are washed with brine, dried with sodium sulphate and concentrated in vacuo. Purification by chromatography on silica gel (hexane/ethyl acetate 10%-20%) gives 12.7 g of 1-(3-fluoro-2-methoxyphenyl)cyclopropylnitrile.

According to the analysis of related databases, 437-82-1, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Berger, Markus; Rehwinkel, Hartmut; Schacke, Heike; Baurle, Stefan; Schmees, Norbert; US2007/225290; (2007); A1;,
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Adding some certain compound to certain chemical reactions, such as: 437-82-1, name is 2,6-Difluoroanisole, 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 437-82-1. 437-82-1

To a solution of l,3-difluoro-2-methoxy-benzene (3.0 g, 20.8 mmol) in tetrahydrofuran (30 mL) at -70 C was added dropwise n-butyl lithium (1.6 g, 25.0 mmol). The reaction was stirred for 30 mins. Then N,N-dimethylformamide (4.6 g, 63 mmol) was added, and stirring was continued for another 30 minute. The cold bath was removed, and the reaction mixture was stirred at 15 C for 1 hour. On completion, the mixture was extracted with ethyl acetate (2 x 15 mL). The aqueous phase was acidified with 4 M hydrochloric acid and extracted with ethyl acetate (3 x 10 mL). The organic phases were combined, dried over sodium sulfate and evaporated in vacuo to give compound B-256 (3.0 g, 84% yield) as a light yellow liquid. LCMS (B): tR=0.624 min., 173.1 m/z (M+l).

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 2,6-Difluoroanisole.

Reference:
Patent; FORUM PHARMACEUTICALS, INC.; ACHARYA, Raksha; BURNETT, Duane, A.; BURSAVICH, Matthew, Gregory; COOK, Andrew, Simon; HARRISON, Bryce, Alden; KOENIG, Gerhard; MCRINER, Andrew, J.; (400 pag.)WO2016/100184; (2016); A1;,
Ether – Wikipedia,
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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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