Month: November 2020

61367-07-5, These common heterocyclic compound, 61367-07-5, name is Methyl trans-4-aminocyclohexanecarboxylate 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.

To a solution of methyl 4-aminocyclohexane carboxylate hydrochloride (1.5 g, 7.74 mmol) and 4-fluoro-3-nitrobenzonitrile (1.28 g, 7.74 mmol) in acetonitrile (50 ml) was added N,N-diisopropylethylamine (2.69 ml, 15.49 mmol) at ambient temperature. The resulting reaction mixture was stirred for 18 hours at room temperature. Acetonitrile was removed under reduced pressure and the crude solid was dissolved in dichloromethane and the dichloromethane layer was washed with water, dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The crude solid product was washed with cold methanol and used in the next step without any further purification. Yield 1.8 g.77% MS (ESI) m/z for C15H17N3O4 = 303.12 (calcd) 304.2 ([M + H]+, found)

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 61367-07-5.

Reference:
Patent; OSLO UNIVERSITY HOSPITAL HF; FORSCHUNGSVERBUND BERLIN E.V.; UNIVERSITY OF OULU; KRAUSS, Stefan; NAZARE, Marc; ANUMALA, Upendra Rao; LEHTIO, Lari; WAALER, Jo; HOLSWORTH, Dan; WEGERT, Anita; LEENDERS, Ruben Gerardus George; (99 pag.)WO2018/118868; (2018); A1;,
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18595-16-9, Name is Methyl 2-amino-5-methylbenzoate, 18595-16-9, belongs to esters-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.

Step 1: To a solution of 2-amino-5-methyl benzoic acid (1.0 mmol) dissolved in 10% MeOH in toluene (2.5 mL) is added dropwise trimethylsilyl-diazomethane (2.0 M in hexanes, 0.75 mL). The reaction mixture is stirred at room temperature for 1 hour and the solvent is removed under reduced pressure. The resulting methyl ester is dissolved in dichloromethane (3.0 mL) and then 4-chlorobenzoyl chloride (1.0 equivalent) and DIEA (1.0 equivalent) is added sequentially. The reaction mixture is stirred for 3 hours and the solvent is evaporated. The yellow residue is diluted with EtOAc, washed with 1 M NaHSO4, brine, dried, filtered and concentrated under reduced pressure to provide 2-(4-chloro-benzoylamino)-5-methyl-benzoic acid methyl ester (compound 11.1) which is used without purification in the next step.

Statistics shows that Methyl 2-amino-5-methylbenzoate is playing an increasingly important role. we look forward to future research findings about 18595-16-9.

Reference:
Patent; Lew, Willard; Baskaran, Subramanian; Oslob, Johan D.; Yoburn, Joshua C.; Zhong, Min; US2006/35908; (2006); A1;,
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Some common heterocyclic compound, 653-92-9, name is Methyl 2-bromo-4-fluorobenzoate, molecular formula is C8H6BrFO2, 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. 653-92-9

To a solution of methyl 2-bromo-4-fluoro-benzoate (90 g, 386.21 mmol, 1 eq) in dimethylsulfoxide (500 mL) was added tert-butyl piperazine-1-carboxylate (111.82 g, 502.07 mmol, 1.3 eq, hydrochloric salt) and N,N-diisopropylethylamine (199.66 g, 1.54 mol, 269 mL, 4 eq). The mixture was heated to 130 C and stirred at 130 C for 36 hours. The mixture was poured into 1.0 L water, and extracted with ethyl acetate (500 mL x 2). The organic layer was washed with water (1000 mL), 0.5 M hydrochloric acid (500 mL), saturated brine (500 mL) and then dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue was triturated with (petroleum ether : ethyl acetate =5:1, 300 mL), the solid was filtered and dried in vacuum. tert-butyl 4-(3-bromo-4-methoxycarbonyl-phenyl)piperazine-1-carboxylate (93 g, 232.92 mmol, 60% yield) was obtained as an off-white solid. LC/MS (ESI) m/z: 422.1 [M+23] +; 1H-NMR (400MHz, DMSO-d6) d 7.73 (d, J=8.8 Hz, 1H), 7.18 (d, J=2.4 Hz, 1H), 6.98 (dd, J=8.8, 2.4 Hz, 1H), 3.77 (s, 3H), 3.45-3.42 (m, 4H), 3.34-3.31 (m, 4H), 1.42 (s, 9H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 653-92-9, its application will become more common.

Reference:
Patent; ARVINAS OPERATIONS, INC.; YALE UNIVERSITY; CREW, Andrew P.; HORNBERGER, Keith R.; WANG, Jing; CREWS, Craig M.; JAIME-FIGUEROA, Saul; DONG, Hanqing; QIAN, Yimin; ZIMMERMAN, Kurt; (1451 pag.)WO2020/51564; (2020); A1;,
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10203-58-4, 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. 10203-58-4, name is Diethyl isobutylmalonate, This compound has unique chemical properties. The synthetic route is as follows.

2-aminotetrahydropyrrolidine hydrochloride (1.33 g, 10 mmoL) was dissolved in 60 mL of anhydrous ethanol, and 1.33 mL of triethylamine was added dropwise with constant stirring, and the reaction was carried out for 10 min at room temperature.A solution of sodium ethoxide (1.36 g, 20 mmoL) in absolute ethanol (20 mL) was added dropwise on an ice bath and allowed to react for 45 min at room temperature after the addition was complete.A solution of diethyl isobutyl malonate (2.16 g, 10 mmoL) in absolute ethanol (20 mL) was added dropwise with constant stirring, and the temperature was raised and refluxed for 15 hours.After TLC tracking, after the reaction was completed, the mixture was filtered by suction and the filtrate was collected. The filtrate was evaporated and the solvent was removed to give a yellow solid.100 mL of water was dissolved and 100 mL of ethyl acetate was extracted three times. Fat-soluble impurities were removed and the aqueous phases were combined.Butanol was extracted and the n-butanol layer was collected, rotary evaporated and the solvent removed to give a pale yellow solid.The trichloromethane was dissolved, suction filtered to remove impurities that were insoluble in chloroform, and the filtrate was collected and spin-dryed to give a white solid as the compound 3-isobutyl-tetrahydropyrrole [1,2-a]pyrimidine-2, 4(1H,3H)-dione.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it.

Reference:
Patent; Xi’an Jiaotong University; Guo Zengjun; Li Dandan; Zhang Jie; Zhang Hui; Liu Xia; Li Mengyi; Xi Ke; (13 pag.)CN104693205; (2017); B;,
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10601-80-6, The chemical industry reduces the impact on the environment during synthesis 10601-80-6, name is Ethyl 3,3-diethoxypropionate, I believe this compound will play a more active role in future production and life.

General procedure: 2-aminopyridine 1a (47 mg, 0.5 mmol), ethyl 3,3-diethoxypropanoate 2 (285 mg, 1.5 mmol) and p-TsOH (8.6 mg, 10 mol %) were stirred in 2 mL of toluene for 6 h at 80 C. After completion of the reaction (monitored by TLC), the water (10 mL) was added. The aqueous solution was extracted with ethyl acetate (3¡Á8 mL) and the combined extract was dried with anhydrous MgSO4. The solvent was removed and the crude product was separated by column chromatography (eluted with petroleum ether/ethyl acetate = 2:1) to give a pure sample of 3a (Yellow crystal, 100 mg, 82%).

The chemical industry reduces the impact on the environment during synthesis Ethyl 3,3-diethoxypropionate. I believe this compound will play a more active role in future production and life.

Reference:
Article; Liu, Wenjie; Wang, Shaohua; Zhan, Haiying; Li, Mingshan; Synlett; vol. 25; 10; (2014); p. 1478 – 1481;,
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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. 1195768-18-3 name is Methyl 3-amino-2-fluorobenzoate, 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. 1195768-18-3

A 500 mL round-bottomed flask was charged with methyl 3-amino-2- fluorobenzoate (20 g, 1 18 mmol) and pyridine (10.52 mL, 130 mmol) in dichloromethane (DCM) (100 mL) to give a yellow/clear solution at 0 C. After 5 min, 1 -propanesulfonyl chloride (13.26 mL, 1 18 mmol) was added to the reaction and warmed to room temperature. After 24 h, the reaction mixture was diluted with EtOAc (200 mL) and concentrated to a volume of 50 mL. The reaction mixture was diluted with EtOAc (200 mL) and water (200 mL) and stirred. After stirring, the EtOAc layer was separated from the water layer. The EtOAc layer was diluted with water (200 mL). After stirring, the EtOAc layer was separated from the water layer. The EtOAc layer was dried over Na2SO4, filtered, and concentrated to 50 mL. While stirring, the reaction mixture was diluted with EtOAc (50 mL) and hexanes (200 mL) and stirred. The solids were filtered and washed with hexanes. The product was put into drying oven for 1 day to obtain methyl 2-fluoro-3- [(propylsulfonyl)amino]benzoate. 28.9 g (105 mmol, 89 % yield) MS: 276 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3-amino-2-fluorobenzoate, and friends who are interested can also refer to it.

Reference:
Patent; GLAXOSMITHKLINE LLC; ADAMS, Jerry, Leroy; FAITG, Thomas; KASPAREC, Jiri; PENG, Xin; RALPH, Jeffrey; RHEAULT, Tara Renae; WATERSON, Alex Gregory; WO2011/59610; (2011); A1;,
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13831-03-3, Name is tert-Butyl propiolate, 13831-03-3, belongs to esters-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.

Step 3: 1 -[4-(tert-Butyl-dimethyl-silanyloxymethyl)-benzyl]-1 H-[1 ,2,3]triazole-4- carboxylic acid tert-butyl ester. Cupric sulfate pentahydrate (1 .03 g, 4.1 1 mmol) and sodium ascorbate (4.07 g, 20.6 mmol) are added to a stirred solution of (4-azidomethyl-benzyloxy)-tert-butyl-dimethy- silane (6.0 g, 20.6 mmol) and tert-butyl propiolate (3.10 ml, 22.6 mmol) dissolved in a mixture of 50 ml of tert-butanol and 50ml of water. The reaction mixture is stirred at room temperature for 2 hours. The solvent is removed under reduced pressure and the residue is partitioned between water and DCM. The organic layer is separated and concentrated under reduced pressure to obtain the crude title compound (Yield 8.3 g). LC (Method 4): tR = 0.73 min; Mass spectrum (ES+): m/z = 404 [M+H]+.

Statistics shows that tert-Butyl propiolate is playing an increasingly important role. we look forward to future research findings about 13831-03-3.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; FRATTINI, Sara; BAKKER, Remko; GIOVANNINI, Riccardo; HAMPRECHT, Dieter; LINGARD, Iain; PAUTSCH, Alexander; WELLENZOHN, Bernd; (92 pag.)WO2017/72020; (2017); A1;,
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Adding some certain compound to certain chemical reactions, such as: 6065-82-3, name is Ethyl diethoxyacetate, 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 6065-82-3. 6065-82-3

I) diethoxyacetic acid To a solution of ethyl diethoxyacetate (5.00 g) in ethanol (20 mL) was added 1M aqueous sodium hydroxide solution (60 mL). The reaction mixture was stirred at room temperature for 2 hr, and ethanol was evaporated under reduced pressure. An aqueous solution of the residue was washed with diethyl ether, and adjusted to pH 3-4 with 2M hydrochloric acid, and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (3.00 g). 1H NMR (400 MHz, CDCl3) delta 1.27 (6H, t, J=7.2 Hz), 3.64-3.77 (4H, m), 4.96 (1H, s), 8.91 (1H, br s).

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 Ethyl diethoxyacetate.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; Kawasaki, Masanori; Mikami, Satoshi; Nakamura, Shinji; Negoro, Nobuyuki; Ikeda, Shuhei; Nomura, Izumi; Ashizawa, Tomoko; Imaeda, Toshihiro; Seto, Masaki; Sasaki, Shigekazu; Marui, Shogo; Taniguchi, Takahiko; (130 pag.)US2016/159808; (2016); A1;,
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1559-02-0, Adding some certain compound to certain chemical reactions, such as: 1559-02-0, name is Diethyl 1,1-cyclopropanedicarboxylate, 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 1559-02-0.

Preparation of ethyl 1-(hydroxymethyl)cyclopropanecarboxylate-A 1M solution of lithium aluminum tri-tert-butoxyhydride in tetrahydrofuran (12 mL, 12 mmol, 2.2 equiv) was added to a stirred solution of diethyl cyclopropane-1,1′-dicarboxylate (1.0 mL, 5.7 mmol, 1.0 equiv) in tetrahydrofuran (19 mL) at 23 C. The resulting solution was heated to 65 C. and stirred for 24 h. The cooled reaction mixture was diluted with a 10% solution of sodium bisulfate (100 mL) and extracted with ethyl acetate (4*50 mL).

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 1559-02-0.

Reference:
Patent; Parker, Marshall H.; Yap, Maurice C.H.; Eckelbarger, Joseph D.; Buysse, Ann M.; Babcock, Jonathan M.; Hunter, Ricky; Adelfinskaya, Yelena; Samaritoni, Jack G.; Garizi, Negar; Trullinger, Tony K.; US2012/53146; (2012); A1;,
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A common compound: 25597-16-4, name is Ethyl 4,4,4-trifluorocrotonate, belongs to esters-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. 25597-16-4

[0179] A mixture of benzaldehyde from Step 1 (3.0 g, 18.07 mmole) and ethyl 4,4, 4- trifluorocrotonate (4.5 g, 27.11 mmole) was dissolved in anhydrous DMF (20 mL), warmed to 60 C and treated with anhydrous K2CO3 (4.99 g, 36.14 mmole). The solution was maintained at 90 C for 24 hours. LCMS analysis indicated that the reaction was complete. After the reaction was cooled to room temperature, the solution was extracted with ethyl acetate. The combined extracts were washed with brine, dried over anhydrous MGS04, filtered and concentrated IRA VACUA to afford brown solid, that was dissolved in MeOH (40 mL) and was precipitated upon adding 13 mL water. The suspension was filtered and dried 1 on vacuum yielding a light brown solid: (4.37 g, 76.6 %): LCMSNL/Z339. 10 (M+Na). H NMR (CDC13/400 MHz) 7.68 (s, 1H), 7.03 (d, 1H, J=8. 7 Hz), 6.50 (d, 1H, J=8. 7 Hz), 5.70 (q, 1H, J=6 Hz), 4.29 (q, 2H, J= 7.2 Hz), 3.84 (s, 3H), 2.09 (s, 3H), 1.33 (t, 3H, J=7. 2 Hz).

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, 25597-16-4, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; PHARMACIA CORPORATION; WO2004/87686; (2004); A2;; ; Patent; PHARMACIA CORPORATION; WO2004/87687; (2004); A1;,
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