Month: January 2021

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 13831-03-3 as follows. Application In Synthesis of tert-Butyl propiolate

To a stirred solution of 3-butyl-3-ethyl-8-hydroxy-2-(4-methoxybenzyl)-7-(methylthio)-5-phenyl-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine 1,1-dioxide (Intermediate 128, 1.0 g, 1.85 mmol) in THF (10 mL) were added DABCO (0.02 g, 0.18 mmol) and t-butyl propiolate (0.28 g, 2.22 mmol) at 0 C. and the reaction mixture was stirred for 1 hour at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with EtOAc (20 mL). The organic layer was washed with water (2¡Á15 mL), dried over anhydrous Na2SO4 and concentrated under vacuum. The resulting crude was purified by Isolera column chromatography (eluent: 15% EtOAc in hexane; silica gel: 230-400 mesh) to afford the title compound. Yield: 49% (0.6 g, white solid). 1H NMR (400 MHz, DMSO-d6): delta 7.66 (d, J=12.3 Hz, 1H), 7.43 (s, 1H), 7.37 (t, J=7.6 Hz, 2H), 7.26 (d, J=8.6 Hz, 2H), 7.20-7.14 (m, 3H), 6.87 (d, J=8.6 Hz, 2H), 6.48-6.25 (m, 1H), 5.27 (d, J=12.1 Hz, 1H), 4.51 (s, 2H), 4.30-4.10 (m, 2H), 3.73 (s, 3H), 2.08 (s, 3H), 1.50-1.36 (m, 13H), 1.18-0.84 (m, 4H), 0.72-0.48 (m, 6H). LCMS: (Method A) 611.2 (M+-tBu+H), Rt. 3.94 min, 98.16% (max).

According to the analysis of related databases, 13831-03-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Albireo AB; Gillberg, Per-Goeran; Mattsson, Jan; Starke, Ingemar; Kulkarni, Santosh S.; (152 pag.)US2019/367467; (2019); A1;,
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Electric Literature of 13412-12-9, 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. 13412-12-9, name is Methyl 3-(methylamino)but-2-enoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Step 2: 2-(4-Bromo-3-methyl-benzoyl)-3-[(E)-methylimino]-butyric acid methyl esterTo 4-bromo-3-methyl-benzoyl chloride (40.0 mmol) in tetrahydrofuran (300 mL) wad added 3-methylamino-but-2-enoic acid methyl ester (5.12 g, 40.0 mmol), followed by pyridine (3.2 mL, 40.0 mmol), and the reaction was stirred overnight at room temperature. Solid pyridine hydrochloride coated the flask, so the mixture was decanted, and the solid was washed three times with EtOAc. The combined solutions were concentrated and diluted with EtOAc (500 mL), and the mixture was washed three times with water. The aqueous layer was separated and back-extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound.

The synthetic route of Methyl 3-(methylamino)but-2-enoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AMIRA PHARMACEUTICALS, INC.; US2010/152257; (2010); A1;,
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Electric Literature of 20921-00-0, 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. 20921-00-0 name is 6-Bromochroman-2-one, 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.

[Step b] To a solution of compound 2 (1.02 g, 4.49 mmol) in tetrahydrofuran (10.0 mL) was added 2 M-aqueous sodium hydroxide solution (5.00 mL), and the mixture was stirred at room temperature for 10 hr. The reaction solution was concentrated under reduced pressure to evaporate the organic solvent, water (10.0 mL) and sodium iodide (1.01 g, 6.74 mmol) were added, and the mixture was cooled to -5C. To the reaction solution was added 2% aqueous sodium hypochlorite solution (20.0 mL) over 40 min, and the mixture was stirred at -5C under cooling for 1 hr. To the reaction solution was added 2 M-aqueous hydrochloric acid solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium thiosulfate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was dissolved in N,N-dimethylformamide (20.0 mL), potassium carbonate (1.86 g, 13.46 mmol) and methyl iodide (0.850 mL, 13.65 mmol) were added, and the mixture was stirred at room temperature overnight. The reaction solution was ice-cooled, 0.1 M-hydrochloric acid (50.0 mL) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography to give compound 4 (1.48 g, 82.6%). MS(ESI)m/z: 399, 401 (M+1)+.

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

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; TAKAHASHI, Taichi; UMINO, Akinori; IIJIMA, Daisuke; TAKAMATSU, Hisayuki; (173 pag.)EP3135667; (2017); A1;,
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Adding a certain compound to certain chemical reactions, such as: 454-31-9, name is Ethyl 2,2-difluoroacetate, belongs to esters-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 454-31-9, Recommanded Product: 454-31-9

To a solution of 1-bromo-4-iodobenzene (28.3 g, 0.100 mol) in anhydrous THF (300 mL) at -78 was added n-BuLi (2.5 M, 44.0 mL, 0.110 mol) , and the resulting mixture was stirred for 30 min before ethyl 2, 2-difluoroacetate (13.6 g, 0.110 mol) was added dropwise. After the addition, the mixture was stirred at -78 for 1 h, then excess base was quenched with aqueous 1N HCl solution (80 mL) . The product mixture was warmed to ambient temperature and extracted with MTBE (400 mL ¡Á 3) . The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated to afford the title compound. MS: m/z 236.2 (M + 1) .1H NMR (400 MHz, DMSO-d6) delta 7.96 (d, J 8.0 Hz, 2H) , 7.85 (d, J 8.0 Hz, 2H), 7.28 -7.02 (m, 1H) .

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

Reference:
Patent; MERCK SHARP & DOHME CORP.; COOKE, Andrew J.; PITTS, Daniel; JOHNSON, Adam; BESHORE, Douglas C.; HURZY, Danielle; MITCHELL, Helen; FRALEY, Mark; MCCOMAS, Casey; SCHIRRIPA, Kathy; MERCER, Swati P.; NANDA, Kausik; MENG, Dongfang; WU, Jane; BABAOGLU, Kerim; LI, Chun Sing; MAO, Qinghua; QI, Zhiqi; (156 pag.)WO2016/54807; (2016); A1;,
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Synthetic Route of 121591-81-9, These common heterocyclic compound, 121591-81-9, name is Methyl 3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate, 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.

K2CO3 (1.79 mmol) is added to a solution of 3,4-dihydro-2H-benzo[1,4]oxazine-5-carboxylic acid methyl ester (0.78 mmol) in DMF (1.0 mL). After 30 min methyl iodide (1.55 mmol) is added and the mixture is stirred for 2 h at 75 C. Cold water and EtOAc are added, the layers are separated and the aq. layer is extracted with EtOAc. The combined organic layers are washed with water and brine, dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS: tR=0.71 min; [M+H]+=208.1.

The synthetic route of 121591-81-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Actelion Phamaceuticals Ltd.; US2010/16401; (2010); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 144267-96-9, name is Ethyl 3,4-difluorobenzoate, belongs to esters-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 144267-96-9, Quality Control of Ethyl 3,4-difluorobenzoate

Intermediate 513-Fluoro-4-(2-methyl-1 H-imidazol-1 -yl)-benzoic acidTo a solution of ethyl 3,4-difluorobenzoate (1 .5 g) in N,N-dimethylformaide (12 mL) is added 2-methylimidazole (1 .3 g) and K2CO3 (2.2 g) and the mixture is heated at 140 C in a microwave oven for 1 h. After cooling to room temperature, water and ethyl acetate are added and the organic layer is dried (MgS04) and concentrated. The residue is purified by chromatography (ethyl acetate/hexane 0: 1?1 :0). The ester is dissolved in methanol (30 mL) and 4 M aqueous NaOH (3 mL) is added and the mixture is stirred at room temperature for 1 h. The mixture is neutralized with 6 M aqueous HCI, concentrated and then acidified with 6 M aqueous HCI. The precipitate is filtered off washing with a small amount of water and dried by suction to give the title compound.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 3,4-difluorobenzoate, and friends who are interested can also refer to it.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; NEUROCRINE BIOSCIENCES, INC.; HECKEL, Armin; BLUM, Andreas; BREITFELDER, Steffen; HIMMELSBACH, Frank; LANGKOPF, Elke; NOSSE, Bernd; WELLENZOHN, Bernd; ASHWEEK, Neil, J.; HARRIOTT, Nicole; WO2012/123449; (2012); A1;,
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Related Products of 394-35-4, 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. 394-35-4, name is Methyl 2-fluorobenzoate, This compound has unique chemical properties. The synthetic route is as follows.

0.06 mol of methyl o-fluorobenzoate,0.022 mol DIC,6.6 mmol DMAP was added to 100 mL dichloromethane, Stirring to continue stirring at room temperature for 30min,Gradually warming to 45 ~ 50 ,The reaction flask was charged with 1-cyclopropanecarbonylpiperazine (0.08 mol)Continue stirring reaction 9 ~ 10h.After the reaction is completed,Cool to 0 C and stir 45min,filter,The filtrate was washed with water (3 * 50 mL)Dried over anhydrous sodium sulfate,The methylene chloride was evaporated under reduced pressure,It was solid,Compound 2 (15.27 g),The yield was 92.57%Purity 99.92%

The chemical industry reduces the impact on the environment during synthesis Methyl 2-fluorobenzoate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Shandong Yuxin Pharmaceutical Co., Ltd.; Liu Zhenteng; Sun Yiwei; Li Hua; Gong Wenju; Wang Libiao; (10 pag.)CN107325055; (2017); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 538372-37-1,Some common heterocyclic compound, 538372-37-1, name is Methyl 3,4-diamino-2-methoxybenzoate, molecular formula is C9H12N2O3, 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.

Compound 63E (1.3 g, 6.6 mmol)And 3,5-dichlorosalicylaldehyde (1.52 g, 7.95 mmol)Stirring in 25 mL of nitrobenzene for two hours, after cooling to room temperature,A large amount of precipitated precipitated, filtered, and the filter cake was washed with petroleum ether.Compound 63F (2.0 g, 85% yield) was obtained.

The synthetic route of 538372-37-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Jiangsu Xiansheng Pharmaceutical Co., Ltd.; Chen Huanming; Liang Bo; Cao Wenjie; Zhang Guiping; Zhao Zhongqiang; Jiang Zhaojian; Zuo Gaolei; Xu Wanmei; Gong Hongju; Zhang Peng; Wang Jianghuai; Li Qingsong; Gao Chunhua; (79 pag.)CN104045552; (2019); B;,
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Electric Literature of 116419-94-4, These common heterocyclic compound, 116419-94-4, name is Methyl 4-methyl-3-(trifluoromethyl)benzoate, 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 solution of 4-methyl-3-trifluoromethylbenzoic acid (1.71 g, 8.37 mmol) in DMF (20 mL) was added with potassium carbonate (1.39 g, 10.1 mmol) and the reaction mixture was stirred at room temperature for five minutes. Iodomethane (0.78 mL, 12.5 mmol) was added and the reaction mixture stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with water and brine (¡Á2). The organic phase was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated at reduced pressure to afford methyl 4-methyl-3-trifluoromethylbenzoate. The material was dissolved in carbon tetrachloride (10 mL) and treated sequentially with N-bromosuccinimide (2.74 g, 15.4 mmol) and benzoyl peroxide (catalytic) and heated at 80 C. for 18 hours. The mixture was allowed to cool and diluted with water. The mixture was poured through a hydrophobic frit and the solvent evaporated at reduced pressure to afford methyl 4-(dibromomethyl)-3-trifluoromethylbenzoate. The material was dissolved in acetone/ water (25 mL/5 mL) and silver nitrate (2.38 g, 14.0 mmol) added. (0223) The reaction mixture was stirred at room temperature for 72 hours. The suspension was filtered through a pad of celite and the filtrate diluted with ethyl acetate. The solution was washed with water and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was dissolved acetone/water (25 mL/5 mL) and silver nitrate (2.38 g, 14.0 mmol) added. (0224) The reaction mixture was stirred at room temperature for 24 hours. The suspension was filtered through a pad of celite and the filtrate diluted with ethyl acetate. The solution was washed with water and brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (eluent-100% i-hexane to 8:1 i-hexane/ ethyl acetate) to afford the title compound (0.537 g, 33%). (0225) 1H NMR (400 MHz, CDCl3); delta 10.46-10.45 (m, 1H), 8.46 (s, 1H), 8.35 (d, J=8.2 Hz, 1H), 8.20 (d, J=8.2 Hz, 1H), 4.00 (s, 3H).

Statistics shows that Methyl 4-methyl-3-(trifluoromethyl)benzoate is playing an increasingly important role. we look forward to future research findings about 116419-94-4.

Reference:
Patent; CHIESI FARMACEUTICI S.P.A.; RANCATI, Fabio; Rizzi, Andrea; Carzaniga, Laura; Linney, Ian; Knight, Chris; Schmidt, Wolfgang; (120 pag.)US2018/16267; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 4934-99-0, name is Methyl 3-hydroxycyclobutanecarboxylate, This compound has unique chemical properties. The synthetic route is as follows., SDS of cas: 4934-99-0

To a solution of methyl 3-hydroxycyclobutanecarboxylate (1.2 g, 9.0 mmol) in DMF (20 mL) was added sodium hydride (60%> wt in mineral oil) (1.8 g, 45 mmol) at RT. The mixture was stirred for 1 h and then 2, 5-difluoro-3-(tetrahydro-pyran-4-yl)-pyridine (1.8 g, 9.0 mmol) was added. The reaction mixture was heated to 60 C for 3 h and then quenched with saturated NH4C1. The solution was diluted with EtOAc and water and extracted with EtOAc (2xl0mL). The organic extracts were combined, washed with brine (lOmL), dried over MgS04, filtered, and concentrated to get a residue, which was purified by flash column chromatography on silica gel (5% to 30%> EtOAc in hexanes) to give the product (3.2 g) as yellow oil.

According to the analysis of related databases, 4934-99-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AMGEN INC.; ALLEN, Jennifer; FROHN, Michael; HARRINGTON, Paul; PICKRELL, Alexander; RZASA, Robert; SHAM, Kelvin; HU, Essa; WO2011/143366; (2011); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics