Month: November 2020

19056-40-7, These common heterocyclic compound, 19056-40-7, name is 4-Bromo-3-methoxyaniline, 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.

Under an atmosphere of nitrogen, in a 100 mL round-bottomed flask at 0¡ã C., 4-bromo-3-methoxyaniline (2 g, 9.9 mmol) and KOH (6.93 ml, 13.9 mmol) were combined with dichloromethane (30 ml) to give a light brown solution. Then 4-bromobutanoyl chloride (1.84 g, 1.15 ml, 9.9 mmol) was added. The reaction was stirred for 1 h at RT. The reaction mixture was poured into 50 ml dichloromethane and extracted with water (3*20 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in 30 ml dichloromethane. Then tetrabutylammonium bromide (63.8 mg, 198 mumol) and KOH (50percent, 6 ml) were added. The reaction was stirred for 1 h at RT. The reaction mixture was poured into dichloromethane (50 ml) and extracted with water (3*20 ml). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 50 g, 20percent to 50percent EtOAc in heptane). The title compound was obtained as a off-white crystalline (1.92 g, 71.8percent). MS (m/e)=272.1 [M+H]+.

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 19056-40-7.

Reference:
Patent; Hoffmann-La Roche Inc.; Jakob-Roetne, Roland; Wichmann, Juergen; Peters, Jens-Uwe; Jagasia, Ravi; (33 pag.)US2016/326150; (2016); A1;,
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Some common heterocyclic compound, 5905-69-1, name is 1-Bromo-4-(difluoromethoxy)benzene, molecular formula is C7H5BrF2O, 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. 5905-69-1

Piperidine-4-carboxylic acid ethyl (3.52mL, 22.9mmol), and 1-Bromo-4- (difluoromethoxy) benzene (4.25g, 19.1mmol) of TorrEne (122 mL) to the solution, sodium tert- butoxide (2.29g, 23.8mmol), palladium acetate (II) (428mg, 1.91mmol), and, tri -tert- butyl phosphine (370muL, 1.52mmol) was added, and 30 minutes at 80 And the mixture was stirred. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, the resulting organic layer was washed with saturated brineAfter, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Siri resulting residue wasGel column chromatography [elution solvent: hexane / ethyl acetate = 100 / 0-90Purification by / 10], the title compound (3.17 g, yield: 56%) was obtained.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5905-69-1, its application will become more common.

Reference:
Patent; Daiichi Sankyo company limited; Sato, Rie; Kobayashi, Katsuhiro; Kaneko, Toshio; (188 pag.)JP2015/113323; (2015); 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 111-95-5 as follows. 111-95-5

The product from step 1 (440 mg, 1.36 mmol) was dissolved in DMF (25 mL), treated with HOBt.H2O (624 mg, 4.08 mmol), and EDC.HCl (786 mg, 4.10 mmol) and stirred for 30 min at room temperature. Bis(2-methoxylethyl)amine (620 mL, 559 mg, 4.20 mmol) was added and the resulting mixture was stirred at room temperature for 16 h and concentrated. The residue was partitioned with water and EtOAc. The EtOAc layer was separated and the aqueous was extracted again with EtOAc. The combined organic layers were washed with 0.5 N HCl, saturated sodium bicarbonate, and brine. The organic layer was dried (Na2SO4), filtered and concentrated to afford 214 mg of 3-(bis(2-methoxyethyl)amino)-6-bromo-N2,N2,N5,N5-tetrakis(2-methoxyethyl)pyrazine-2,5-dicarboxamide (26% yield) as a brown oil: LCMS (5-95% gradient acetonitrile in 0.1% TFA over 10 min), single peak retention time=3.85 min on 30 mm column, (M+H)+=608.

According to the analysis of related databases, 111-95-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MediBeacon Inc.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (52 pag.)US2019/125902; (2019); A1;,
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A common compound: 111-95-5, name is Bis(2-methoxyethyl)amine, belongs to ethers-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below. 111-95-5

General procedure: General procedure B: To a mechanically stirred solution of bis(2-methoxyethyl)amine (39.96 g, 0.3 mol) in dichloromethane (100 mL), was added dropwise n-butyllithium (1.6 M in n-hexane, 187.5 mL, 0.3 mol) at -78 C under an argon atmosphere. After further stirring for 5 min, pentafluoroethanesulfonyl fluoride (2, 20.21 g, 0.1 mol) was added and the mixture was stirred for 1 h. Then the cryopump was removed, and allow the mixture stand at room temperature. The subsequent procedures exactly followed those in the procedure A.

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, 111-95-5, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Fu, Shi-Tao; Liao, Shuai-Ling; Nie, Jin; Zhou, Zhi-Bin; Journal of Fluorine Chemistry; vol. 147; (2013); p. 56 – 64;,
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134364-69-5, The chemical industry reduces the impact on the environment during synthesis 134364-69-5, name is 2,3-Difluoroanisole, I believe this compound will play a more active role in future production and life.

The first step: 1000mL four-neck flask, equipped with a thermometer and a condenser tube, under nitrogen protection, put in 2,3-difluoroanisole 57.6g (0.4mol) and 440mL of tetrahydrofuran, start stirring, and lower the temperature to -85 At -75 C, 192 mL (0.48 mol) of n-butyl lithium in hexane solution (2.5 mol / L) was slowly added dropwise. After the addition was completed, the temperature was controlled and stirred for 2.0 hours. After the heat preservation is completed, the temperature is controlled from -85 C to -75 C, and 62.3g (0.6mol) of trimethyl borate is added dropwise. Sample delivery liquid phase detection of 2,3-difluoroanisole raw material residue <0.5%.After the reaction is completed, dehydrolyze tetrahydrofuran under negative pressure until the temperature of the reaction flask reaches 50 C without flow, stop the desolvation, cool to 20-25 C, add 520mL of pure water, control temperature 20-25 C and drop 133.3g (1.0 mol), the dropwise addition was completed and kept stirring for 1.0 hour. 172.8g toluene was added for extraction, the toluene phase was stored separately for use, and the aqueous phase was directly oxidized without further purification. Recover 430.5g of desolvent, send sample to detect water 0.02%, tetrahydrofuran: n-hexane mass ratio is about 4: 1, methanol content is 1.5%, need to remove methanol to apply. The chemical industry reduces the impact on the environment during synthesis 2,3-Difluoroanisole. I believe this compound will play a more active role in future production and life. Reference:
Patent; Bengbu Zhong Shi Chemical Co., Ltd.; Xu Jianxiao; Liu Hongqiang; Zhao Shimin; Wei Jiayu; Wang Songsong; Zhu Keming; (7 pag.)CN110922306; (2020); A;,
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1462-37-9, These common heterocyclic compound, 1462-37-9, name is ((2-Bromoethoxy)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.

Step b: Ethyl 1 -(2-(benzyloxy)ethyl)-4-(terf-butyldimethylsilyloxy)cyclohexanecarboxylate; [00165] To a mixture of the compound of Step a (102 g, 0.357mol) in THF (800 mL) at -78 0C was added lithium bis(tritnethylsiyl)amide (438 mL) dropwise under nitrogen. The mixture was stirred for 30 min followed by the addition of benzyl 2-bromoethyl ether (109 mL, 0.375mol). After stirring the mixture for another 30min at -78 ¡ãC, the reaction mixture was allowed to warm up to room temperature and stirred for 1 h. The mixture was diluted with ethyl acetate (1,000 mL) and washed with brine (1,000 mL), dried over Na2SO4 and filtered. The filtrate was concentrated to give a crude product which was purified by flash chromatography (silica gel, EtOAc/Hexane: 0/1 to 1/1) to give the ester-benzylether as a colorless oil (1 15 g, 73percent).

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 1462-37-9.

Reference:
Patent; BIOGEN IDEC MA INC; WO2007/76086; (2007); A2;,
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1484-26-0, Adding some certain compound to certain chemical reactions, such as: 1484-26-0, name is 3-Benzyloxyaniline, 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 1484-26-0.

2-Ohtoeroethyl isothiocyanate (293 ing, 2.4 mroot) was added io a solution of 3~bepsilonnzy)oxy~pheny)amine (398 mg, 2,0 mmoi) in dicMoromethane (4 mL), The reaction mixture was stirred at room temperature overnight It was quenched with water (30 mL), followed by extraction with diehloromethane OO mL x 3 ), The organic layers were combined, washed with brine, and concentrated under vacuum. The residue thus obtained was subjected to column chromatography on silica gel to give l -(3-benlambda’ioxy-plienyl)-3-{2-chloro-ethyl)-{hioufea (627 mg, 1.96 mmoi. yield; 98percent) as colorless oil.Tricihylarmne (2.0 mL, excess) was added to a solution of i ~(3-be”zyloxy- phctty.)-3-(2-chloro-ethyl)-mionrea ( S 87 mg, 0.58 mmol} in dry THF (3 mL). The reaction mixture was stirred at refluxiog temperature for 6 hours. It was then quenched with a saturated ammonium chloride aqueous solution {30 niL), followed by extraction with ethyl acetate (30 mL x 3), The organic layers were combined, washed with brine, and concentrated under vacuum. The residue thus obtained was subjected Jo column chromatography on silica gei to give l-(3-benz.yloxy~phenyl>- imidazoiidine-2-thione (compound 76) as a white solid (150 mg. 0.52 mmoi, yield: 90percent).Fi-MS (M-M ): 285.

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 1484-26-0.

Reference:
Patent; NATIONAL HEALTH RESEARCH INSTITUTES; WO2008/22204; (2008); A2;,
Ether – Wikipedia,
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20781-20-8, 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. 20781-20-8, name is (2,4-Dimethoxyphenyl)methanamine, A new synthetic method of this compound is introduced below.

To a solution of 5-fluoro-2-nitrobenzoic acid (6.6 g,35.66 mmol) in dichloromethane (100 mL) were added DIPEA (9.22 g, 71.3 mmol), HOSt (6.0 g, 39.2 mmol) and EDCI (10.2 g, 53.5 mmol). After about 15 mm stirring, to the reaction mixture was added a solution of 2,4-dimethoxy- benzyl amine (5.96 g, 35.66 mmol) in dichloromethane (50 mL) dropwise under nitrogen atmosphere. The resulting mixture was stirred under nitrogen atmosphere at room temperature for 16 h. The reaction mixture was washed successively with iN HC1 (100 mL), sat. NaHCO3 (100 mL) and brine (100 mL). The organic phase was then dried over MgSO4. Filtration and solvent removal in vacuo afforded a yellowish solid, wt: 9.3 g (78%). MS: [M+1]=335.

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; AgeneBio, Inc.; Mekonnen, Belew; Butera, John A.; Huang, Jianxing; (331 pag.)US2018/170941; (2018); A1;,
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1535-73-5, name is 3-Trifluoromethoxyaniline, 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. 1535-73-5

As shown in Scheme 4, Compound 3 was prepared in the following manner. To a solution of 2-methyl-1-(3-morpholinopropyl)-5-phenyl-1H-pyrrole-3-carboxylic acid 7 (100 mg; 0.305 mmol) in 5 mL DCM was added thionyl chloride (111 muL; 1.53 mmol) and DMF (20 muL). After stirring for 3 h at rt, the reaction mixture was evaporated and dried under vacuum. To the residue was added DCM (3 mL), 3-trifluoromethoxyaniline 11 (108 mg; 0.61 mmol), and DIPEA (0.22 mL; 1.2 mmol), and the reaction mixture was stirred overnight. To the reaction mixture was added water, and the mixture was extracted with DCM. The organic phase was washed with water, brine, dried by anhydrous sodium sulfate, concentrated, and purified by chromatography to provide Compound 3 (99 mg; 0.203 mmol, 67percent yield). 1H-NMR (CD3OD/400 MHz): delta 7.80 (s, 1H); 7.58 (d, 1H); 7.40 (m, 6H); 6.96 (d, 1H); 6.65 (s, 1H); 4.08 (m, 2H); 3.57 (m, 4H); 2.64 (s, 3H); 2.30 (m, 6H); 1.67 (m, 2H). 19F-NMR (CD3OD/376 MHz): ?59.73 (s). MS (ES+, m/z): 488.0 (M++1, 100.0).

Statistics shows that 1535-73-5 is playing an increasingly important role. we look forward to future research findings about 3-Trifluoromethoxyaniline.

Reference:
Patent; Krizaj, David; Prestwich, Glenn D.; Barabas, Peter; Xu, Yong; Ryskamp, Daniel; US2013/303539; (2013); 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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