Esters-buliding-blocks

Some common heterocyclic compound, 105-53-3, name is Diethyl malonate, molecular formula is C7H12O4, 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. 105-53-3

To a solution of diethyl malonate (3.2 g, 20 mmol) and anhydrous potassium carbonate powder (6.9 g, 50 mmol) in DMF (50.0 mL) was added 1,2-dibromoethane (4.136 g, 22 mmol). After stirring for 2 hrs, catalytic amount of TBAI (0.738 g, 2.0 mmol) was added and the mixture was continued to stir at room temperature for 8 hrs. The reaction mixture was filtered and the solid was washed with diethyl ether 3 times. The filtrate was diluted with water (200 mL) and extracted with diethyl ether (75 mL*4). The combined organic phases were washed with 70 mL of brine, dried over Na2SO4 and concentrated in vacuo. The residue was chromatographed with a short alumina column (1: 10 (v/v) EtOAc / n-hexane) to afford the desired compound as yellow oil (3.3 g, 88.7 %). 1H NMR (400MHz, CDCl3): delta 1.27 (m, J=6.8Hz, 6H), 1.42 (m, 4H), 4.18 (m, 4H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 105-53-3, its application will become more common.

Reference:
Patent; Sunshine Lake Pharma Co., Ltd.; Xi, Ning; XI, Ning; (152 pag.)EP2408300; (2016); B1;,
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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. 344-14-9, name is Dimethyl 2-fluoromalonate, A new synthetic method of this compound is introduced below., 344-14-9

General procedure: In a 50 mL two-necked flask containing dichloromethane (10 mL) were added the amine (17 mmol) followed by the aldehyde (15 mmol) and the resulting reaction mixture was allowed to stir at rt for 2 h, before the fluorinated dicarbonyl system (10 mmol) was added. The reaction mixture was stirred at rt for 16 h, evaporated and the residue dissolved in dichloromethane (20 mL), washed with distilled water (2¡Á20 mL), dried over magnesium sulfate and evaporated, to give the desired product. Further purification by distillation or column chromatography eluting from hexane/ethyl acetate was carried out when appropriate. Analytical and spectroscopic data for each individual compound are listed below. For NMR data only resonances of one diastereoisomer or conformer is given for clarity.

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:
Article; Lisse, Etienne; Sandford, Graham; Journal of Fluorine Chemistry; vol. 206; (2018); p. 117 – 124;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

3196-15-4, 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 3196-15-4 as follows.

Potassium carbonate (8.7 g, 63 mmol) was added to a solutionof 3-bromo-8-methylquinolin-6-ol (7, 5.0 g, 21 mmol) in 70 ml ofN,N-dimethylformamide. After the addition of methyl 2-bromobutyrate(7.1 g, 38 mmol), the reaction mixture was stirred for 16 h atroom temperature. Subsequently the mixture was filtered and thefiltrate was diluted with ethyl acetate. This organic phase waswashed with water and brine, dried over magnesium sulfate andevaporated under reduced pressure. The residue was purified bychromatography on silica gel, using ethyl acetate and cyclohexaneas eluents to yield 2-(3-bromo-8-methylquinolin-6-yloxy)-butyricacid methyl ester (8, 6.5 g, 19 mmol, 91%). 1H NMR (CDCl3):d = 1.04 (t, 3H, J = 7.3 Hz), 1.99 (q, 2H, J = 7.1 Hz), 2.68 (s, 3H),3.70 (s, 3H), 4.63 (t, 1H, J = 7.7 Hz), 6.65 (d, 1H, J = 2.3 Hz), 7.22(d, 1H, J = 2.2 Hz), 8.06 (d, 1H, J = 2.1 Hz), 8.68 (d, 1H, J = 2.1 Hz).LC-MS: Rt = 1.12 min; MS: m/z = 340 [M+1]+, 341 [M+2]+.

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

Reference:
Article; Lamberth, Clemens; Kessabi, Fiona Murphy; Beaudegnies, Renaud; Quaranta, Laura; Trah, Stephan; Berthon, Guillaume; Cederbaum, Fredrik; Knauf-Beiter, Gertrud; Grasso, Valeria; Bieri, Stephane; Corran, Andy; Thacker, Urvashi; Bioorganic and Medicinal Chemistry; vol. 22; 15; (2014); p. 3922 – 3930;,
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653-92-9, 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. 653-92-9 name is Methyl 2-bromo-4-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.

Into a 250-mL round-bottom flask, was placed a solution of Example 1-i, i.e, 1- [[2-(4-chlorophenyl)-4,4-dimethylcyclohex- i-en-i -ylj methyljpiperazine (15.09 g, 47.32 mmol, 1.00 equiv) in DMA (150 mL), DIEA (12.9 g, 99.81 mmol, 2.00 equiv), methyl 2-bromo-4-fluorobenzoate (11.6 g, 49.78 mmol, 1.00 equiv). The resulting solution was stirred for 12 h at 100 degree. The reaction mixture was cooled to room temperature. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3xiOO mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3xiOO mL of brine. The mixture was dried over anhydrous sodium sulfate, then filtered and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (0:1-1:5). This resulted in 7 g (crude) of methyl 2-bromo-4-(4-[[2- (4-chlorophenyl)-4,4-dimethylcyclohex- i-en-i -ylj methyljpiperazin- 1 -yl)benzoate as yellow oil. LC-MS: (ES, m/z): M+i=533, 531.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 2-bromo-4-fluorobenzoate, and friends who are interested can also refer to it.

Reference:
Patent; NEWAVE PHARMACEUTICAL INC.; CHEN, Yi; LOU, Yan; (108 pag.)WO2019/40550; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 889858-12-2, name is tert-Butyl 4-bromo-2-fluorobenzoate, molecular formula is C11H12BrFO2, 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. 889858-12-2

To a 50 mL round-bottom flask was added Cs2CO3 (480 mg, 1.47 mmol, 3.00 equiv.), toluene (4 mL), tert-butyl 4-bromo-2-fluorobenzoate (162 mg, 0.59 mmol, 1.20 equiv.), 5-[[4- cyclopropyl-l-(2,6-dichlorophenyl)-1H-pyrazol-5-yl]methoxy]-3-ethyl-2- azabicyclo[2.2.1]heptane trifluoro acid acid salt 16b (200 mg, 0.49 mmol, 1.00 equiv.), Ruphos (82.3 mg, 0.20 equiv.), and Rupos preacatalyst (46 mg, 0.20 equiv.). The resulting mixture was heated at 110¡ãC overnight. After cooling to room temperature, the mixture was diluted with H2O (50 mL), extracted with ethyl acetate (100 mL x 2), and the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography eluting with ethyl acetate/hexane (1/3) to afford tert-butyl 4-(5-[[4-cyclopropyl-l-(2,6-dichlorophenyl)-1H-pyrazol-5- yl]methoxy]-3-ethyl-2-azabicyclo[2.2.1]heptan-2-yl)-2-fluorobenzoate 18a(180 mg, 61percent) as a yellow oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 889858-12-2, its application will become more common.

Reference:
Patent; ARDELYX, INC.; CHAO, Jianhua; (231 pag.)WO2019/55808; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

344-14-9, Name is Dimethyl 2-fluoromalonate, 344-14-9, 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.

General procedure: In a 50 mL two-necked flask containing dichloromethane (10 mL) were added the amine (17 mmol) followed by the aldehyde (15 mmol) and the resulting reaction mixture was allowed to stir at rt for 2 h, before the fluorinated dicarbonyl system (10 mmol) was added. The reaction mixture was stirred at rt for 16 h, evaporated and the residue dissolved in dichloromethane (20 mL), washed with distilled water (2¡Á20 mL), dried over magnesium sulfate and evaporated, to give the desired product. Further purification by distillation or column chromatography eluting from hexane/ethyl acetate was carried out when appropriate. Analytical and spectroscopic data for each individual compound are listed below. For NMR data only resonances of one diastereoisomer or conformer is given for clarity.

Statistics shows that Dimethyl 2-fluoromalonate is playing an increasingly important role. we look forward to future research findings about 344-14-9.

Reference:
Article; Lisse, Etienne; Sandford, Graham; Journal of Fluorine Chemistry; vol. 206; (2018); p. 117 – 124;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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 1186-73-8 as follows. 1186-73-8

Step 11; 8-fluoro-4-hvdroxv-9-methyl-2-oxo-l,2,5,6,7,9- hexahydropyrido [3′,2′ :6,7] cyclohepta [l,2-f]indole-3-carboxylic acid The N-(10-fluoro-l-methyl-6,7,8,9-tetrahydrocyclohepta[f]indol-5(lH)-ylidene)-2- methylpropan-2-amine obtained above (ca. 2.22 mmol) and trimethyl methanetricarboxylate (0.72 g, 3.79 mmol) were mixed together in Ph20 (5 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min. The reaction mixture was cooled to room temperature. The precipitate was filtered, then washed with ether, to give a crude product (22 mg, 3%) which was used directly in the next step without further purification. LC-MS 357.1 [M+H]+, RT 1.38 min.

According to the analysis of related databases, 1186-73-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; PTC THERAPEUTICS, INC.; BRANSTROM, Arthur; JOSYULA, Vara Prasad, Venkata Nagendra; ARNOLD, Michael, Andrew; GERASYUTO, Aleksey, I.; KARP, Gary; WANG, Jiashi; WO2013/33228; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

344-14-9, 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. 344-14-9, name is Dimethyl 2-fluoromalonate, A new synthetic method of this compound is introduced below.

(8R, 8S)-3-Fluoro-2-hydroxy-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H- pyrimido[1 ,2-a]pyrimidin-4-one can be prepared in the following way. 5.6 g of sodium methoxide are added to a suspension of 7 g of (4R,4S)-4-(trifluoromethyl)-1 ,4,5,6-tetrahydropyrimidin-2-ylamine hydrochloride in 35 ml of dimethyl fluoropropanedioate. After stirring the suspension for 3 hours at a temperature of 100C, the medium obtained is concentrated to dryness under reduced pressure. The residue is taken up in diethyl ether and then dried with suction under vacuum. The solid obtained is taken up in 14 ml of water, and the resulting mixture is cooled in ice, before acidification to pH 5-6 by addition of concentrated hydrochloric acid (25%). After 2 hours of stirring at a temperature of 0C and then overnight at a temperature of about 20C, the suspension is filtered and then the solid is dried with suction and dried under vacuum over P2O5. 6.5 g of (8R, 8S)-3- fluoro-2-hydroxy-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1 ,2- a]pyrimidin-4-one are obtained in the form of a yellow powder, the characteristics of which are the following: Mass spectrum (method A) (ES +/-) [M+H]+: m/z 254; [M-H]-: m/z 252; Tr (min) = 0.28

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; SANOFI; EL-AHMAD, Youssef; FILOCHE-ROMME, Bruno; LETALLEC, Jean-Philippe; MARCINIAK, Gilbert; RONAN, Baptiste; VIVET, Bertrand; WO2013/190510; (2013); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

A common compound: 4341-76-8, name is Ethyl 2-butynoate, 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. 4341-76-8

General procedure: In a two neck rbf was stirred a mixture of Pd(OAc)2 (275 mg,1.22 mmol) and TDMPP (540 mg, 1.22 mmol) in benzene (30 ml)for 15 min at rt under nitrogen. To this mixture was added ethyl-2-butynoate 7 (2.84 ml, 24.48 mmol) and the resulting mixturewas further stirred for 10 min at rt. Next, ethynylbenzene 4a(2.50 g, 24.48 mmol) was added to this solution and the mixturewas stirred for 5-10 min until reaction was completed. Theworkup of reaction was performed by evaporating the solvent invacuum followed by column chromatography (Hexane:EtOAc = 100:1) to give the desired compound 8a (2.62 g);

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, 4341-76-8, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Singh, Sarbjit; Goo, Ja-Il; Noh, Hyojin; Lee, Sung Jae; Kim, Myoung Woo; Park, Hyejun; Jalani, Hitesh B.; Lee, Kyeong; Kim, Chunsook; Kim, Won-Ki; Ju, Chung; Choi, Yongseok; Bioorganic and Medicinal Chemistry; vol. 25; 4; (2017); p. 1394 – 1405;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

1195768-18-3, A common heterocyclic compound, 1195768-18-3, name is Methyl 3-amino-2-fluorobenzoate, molecular formula is C8H8FNO2, 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 the reaction flask were added methyl 2-fluoro-3-aminobenzoate (20 g, 118.23 mmol), bromomethylcyclopropane (20.75 g, 153.70 mmol), N,N-dimethylformamide (200 mL) , stirred under reflux for 16 h, monitored by TLC to reactionWhen not in progress, turn off the heat and end the reaction. After the reaction mixture was cooled to room temperature, water (200 mL) was added, and the mixture was evaporated.Purification by column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) afforded pale-yellow liquid product 2-fluoro-(3-(cyclopropylmethyl)amino)benzoic acid methyl ester (13 g, yield 49.39%).

The synthetic route of 1195768-18-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Shanghai Taihe International Trade Co., Ltd.; Lv Liang; Liu Jiyong; Xiang Juncheng; Ma Wenjing; Zhou Liqi; Hou Shuang; Ni Jueping; Li Zongcheng; (56 pag.)CN108586279; (2018); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics