Month: November 2020

344-14-9,Some common heterocyclic compound, 344-14-9, name is Dimethyl 2-fluoromalonate, molecular formula is C5H7FO4, 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 stirred solution of dimethyl fluoromalonate (1 mmol, 150.11 mg) in anhydrous methanol (10 ml) was added a solution of n-octylamine (1 mmol, 166 mul) in methanol (5 ml) drop wise over the period of one hour at room temperature. It was then further stirred at room temperature for two hours. The solution was rotary evaporated and the residue redissolved in ethyl acetate. The ethyl acetate solution was sequentially washed with 2 M HCI (2×10 ml) and saturated sodium chloride (1×15 ml) solution. Drying over MgSO4 and rotary evaporation of organic solvent gave white solid that was a mixture of bisamide and ethyl 4-aza-2-fluoro-3-oxododecanoate. Desired product was purified as a white solid by PLC in 40-60 petroleum ether – diethyl ether (3:2), (117 mg, 47%).TLC Rf 0.23, petroleum ether- diethyl ether (3:2)1H NMR (400 MHz, CDCI3) delta 0.88 (3H, t, J 6.4 Hz, (CH3(CH2)/), 1.29 (10H, m, CH3(CH2)5), 1.54 (2H, br s, CH3(CH2)5CH2), 3.32 (2H, m, J 6.6 Hz, CH3(CH2)6CH2), 3.9 (3H, s, OCH3), 5.28 (1 H, d, J 49.2, C(H)F), 6.42 (1 H, s, NH).

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

Reference:
Patent; THE UNIVERSITY OF NOTTINGHAM; WO2007/135466; (2007); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

25542-62-5, A common compound: 25542-62-5, name is Ethyl 6-bromohexanoate, 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.

Example 9 Synthesis of 3-[3-(5-carboxypentyl)-5-iodo-2,3-dimethyl-3H-1-indoliumyl]-1-propanesulfonate (2) A mixture of 13.4 g (0.12 mol) of potassium tert-butoxide and 100 g of tert-butanol was stirred and heated until the tert-butoxide totally dissolved. The solution was cooled to about 50 C. and 17 g (0.12 mmol) of ethyl 2-methylacetoacetate was added dropwise. Ethyl-6-bromohexanoate (30 g, 0.13 mmol) was then added dropwise and the reaction mixture was stirred and refluxed for 5 hours. The mixture was filtered and the solvent was removed under reduced pressure. The residue was partitioned between 1M HCl and chloroform. The organic layer was dried over magnesium sulfate and purified on silica gel using 1:10 ethyl acetate/hexane as the eluent to yield 25 g (75%) of diethyl 2-acetyl-2-methyloctanedioate (3) as yellow liquid.

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 6-bromohexanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NANOQUANTUM SCIENCES, INC.; Jones, Gary W.; Tatarets, Anatoliy L.; Patsenker, Leonid D.; US2013/231604; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

2318-25-4, 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. 2318-25-4, name is Ethyl 3-ethoxy-3-iminopropionate hydrochloride belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A 5000 ml_, 4-neck flask was fitted with a stirrer, thermometer, condenser, and gas inlet/outlet. The equipped flask was charged with 265.7 g (1.12 mol. 1.0 eq) of 5-(4-methyl-piperazin-1-yl)-2-nitroaniline and 2125 ml_ of 200 proof EtOH. The resulting solution was purged with N2 for 15 minutes. Next, 20.0 g of 5percent Pd/C (50percent H2O w/w) was added. The reaction was vigorously stirred at 40-500C (internal temperature) while H2 was bubbled through the mixture. The reaction was monitored hourly for the disappearance of 5-(4- methyl-piperazin-1-yl)-2-nitroaniline by HPLC. The typical reaction time was 6 hours.[0091] After all the 5-(4-methyl-piperazin-1-yl)-2-nitroaniline had disappeared from the reaction, the solution was purged with N2 for 15 minutes. Next, 440.0 g (2.25 mol) of ethyl 3-ethoxy-3-iminopropanoate hydrochloride was added as a solid. The reaction was stirred at 40-50¡ãC (internal temperature) until the reaction was complete. The reaction was monitored by following the disappearance of the diamino compound by HPLC. The typical reaction time was 1-2 hours. After the reaction was complete, it was cooled to room temperature and filtered through a pad of Celite filtering material. The Celite filtering material was washed with absolute EtOH (2 x 250 mL), and the filtrate was concentrated under reduced pressure providing a thick brown/orange oil. The resulting oil was taken up in 850 mL of a 0.37percent HCI solution. Solid NaOH (25 g) was then added in one portion, and a precipitate formed. The resulting mixture was stirred for 1 hour and then filtered. The solid was washed with H2O (2 x 400 mL) and dried at 50¡ãC in a vacuum oven providing 251.7 g (74.1 percent) of [6-(4-methyl-piperazin-1-yl)- 1 H-benzoimidazol-2-yl]-acetic acid ethyl ester as a pale yellow powder.; A 5000 mL, 4-neck jacketed flask was fitted with a mechanical stirrer, condenser, temperature probe, gas inlet, and oil bubbler. The equipped flask was charged with 300 g (1.27 mol) of 5-(4-methyl-piperazin-1-yl)-2- nitroaniline and 2400 mL of 200 proof EtOH (the reaction may be and has been conducted with 95percent ethanol and it is not necessary to use 200 proof ethanol for this reaction). The resulting solution was stirred and purged with N2 for 15 minutes. Next, 22.7 g of 5percent Pd/C (50percent H2O w/w) was added to the reaction flask. The reaction vessel was purged with N2 for 15 minutes. After purging with N2, the reaction vessel was purged with H2 by maintaining a slow, but constant flow of H2 through the flask. The reaction was stirred at 45-55¡ãC (internal temperature) while H2 was bubbled through the mixture until the 5-(4-methyl- piperazin-1-yl)-2-nitroaniline was completely consumed as determined by HPLC. The typical reaction time was 6 hours.[0093] After all the 5-(4-methyl-piperazin-1-yl)-2-nitroaniline had disappeared from the reaction, the solution was purged with N2 for 15 minutes. The diamine intermediate is air sensitive so care was taken to avoid exposure to air. 500 g (2.56 mol) of ethyl 3-ethoxy-3-iminopropanoate hydrochloride was added to the reaction mixture over a period of about 30 minutes. The reaction was stirred at 45-550C (internal temperature) under N2 until the diamine was completely consumed as determined by HPLC. The typical reaction time was about 2 hours. After the reaction was complete, the reaction was filtered while warm through a pad of Celite. The reaction flask and Celite were then washed with 200 proof EtOH (3 x 285 ml_). The filtrates were combined in a 5000 mL flask, and about 3300 ml_ of ethanol was removed under vacuum producing an orange oil. Water (530 mL) and then 1 M HCL (350 ml_) were added to the resulting oil, and the resulting mixture was stirred. The resulting solution was vigorously stirred while 30percent NaOH (200 mL) was added over a period of about 20 minutes maintaining the internal temperature at about 25-30¡ãC while the pH was brought to between 9 and 10. The resulting suspension was stirred for about 4 hours while maintaining the internal temperature at about 20-250C. The resulting mixture was filtered, and the filter cake was washed with H2O (3 x 300 mL). The collected solid was dried to a constant weight at 50¡ãC under vacuum in a vacuum oven providing 345.9 g (90.1percent) of [6-(4-methyl-piperazin-1-yl)-1 H- benzoimidazol-2-yl]-acetic acid ethyl ester as a pale yellow powder. In an alternative work up procedure, the filtrates were combined and the ethanol was removed under vacuum until at least about 90percent had been removed. Water at a neutral pH was then added to the resulting oil, and the solution was cooled to about 0¡ãC. An aqueous 20percent NaOH solution was then added slowly with rapid stirring to bring the pH up to 9.2 (read with pH meter). The resulting mixture was then filtered and dried as described above. The alternative work up procedure provided the light tan to light yellow product in yields as high as 97percent.

The synthetic route of Ethyl 3-ethoxy-3-iminopropionate hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; WO2008/112509; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

24398-88-7, Adding a certain compound to certain chemical reactions, such as: 24398-88-7, name is Ethyl 3-bromobenzoate, 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 24398-88-7.

The N-(3-amino-4-methylphenyl)-3-morpholinobenzamide used as a starting material was prepared as follows: A mixture of ethyl 3-bromobenzoate (1.92 ml), morpholine (1.25 ml), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.336 g), sodium tert-butoxide (1.615 g) and tris(dibenzylideneacetone)dipalladium(0) (0.33 g) and toluene (25 ml) was stirred and heated to 90 C. for 18 hours under argon. The reaction mixture was allowed to cool to ambient temperature and extracted with 1M hydrochloric acid. The aqueous phase was basified with concentrated sodium hydroxide solution and extracted with ethyl acetate. The organic phase was dried over magnesium sulphate, filtered and evaporated to dryness. The residual oil was purified by column chromatography on silica gel using a 47:3 mixture of methylene chloride and methanol as eluent to yield N-(3-morpholinobenzoyl)morpholine (0.45 g).

According to the analysis of related databases, 24398-88-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Astrazeneca AB; US6593333; (2003); B1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

426-65-3, name is Ethyl Pentafluoropropionate, 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. 426-65-3

P-xylene (30 mL) of ethyl 2,2,3,3,3-pentafluoropropanoate (S-1) (7.69 g, 40.0 mmol)1,3-diaminopropan-2-ol (S-2) (3.61 g, 40.0 mmol) was added to the solution, and the mixture was stirred at 160 C. for 4 hours.The solvent was distilled off under reduced pressure,Compound (S-3) (yield: 10.1 g)As a yellow oil.

Statistics shows that 426-65-3 is playing an increasingly important role. we look forward to future research findings about Ethyl Pentafluoropropionate.

Reference:
Patent; Kaken Pharmaceutical Co., Ltd.; Watanabe, Atsushi; Sato, Yuki; ogura, Keiji Tamada; Tatsumi, Yoshiyuki; (283 pag.)JP2018/145180; (2018); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 57381-43-8, name is Methyl 2,5-dibromobenzoate, molecular formula is C8H6Br2O2, 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. 57381-43-8

General procedure: A mixture of magnesium turnings (0.036g, 1.5mmol), bromobenzene (0.15g, 1mmol), tri-n-butyltin chloride (0.49g, 1.5mmol) and 1,2-dibromoethane (0.094g, 0.5mmol) as initiator in dry THF (5mL) was sonicated for 1h in an ultrasonic cleaning bath at around 35¡ãC, with monitoring of the reaction by TLC. Once the reaction finished, aqueous saturated NH4Cl solution (40mL) was added and extracted with ethyl acetate (3¡Á20mL). The combined extracts were washed with brine (60mL) and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the product was isolated by column chromatography with silica gel doped with 10percent of KF to retain tri-n-butyltin halides formed during the reaction. 4 (0.286, 0.78mmol, 78percent) eluted with 98:2 (hexane/diethyl ether).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 57381-43-8, its application will become more common.

Reference:
Article; Gerbino, Dario C.; Fidelibus, Pablo M.; Mandolesi, Sandra D.; Ocampo, Romina A.; Scoccia, Jimena; Podesta, Julio C.; Journal of Organometallic Chemistry; vol. 741-742; 1; (2013); p. 24 – 32;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

455-75-4, These common heterocyclic compound, 455-75-4, name is Ethyl 3-amino-4-fluorobenzoate, 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 Ethyl 4-fluoro-3-methoxyacetamido-benzoate A solution of 2.8 g (15.3 mMol) of ethyl 3-amino-4-fluoro-benzoate (cf. L. S. Fosdick, A. F. Dodds in J. Amer. Chem. Soc. 65, 2305 (1943)) and 1.56 ml (1.85 g=17.0 mMol) of methoxyacetylchloride in 50 ml chlorobenzene was stirred for 1 hour at 50 C. and then refluxed for 15 minutes. Then the solvent was distilled off in vacuo and the crude product obtained was purified by flash chromatography (silica gel; dichloromethane/ethanol=100:1). The desired compound, initially oily, solidified within a few days. Yield: 3.8 g (98% of theory), Rf value: 0.38 (silica gel; dichloromethane/ethanol=19:1)

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 455-75-4.

Reference:
Patent; Boehringer Ingelheim Pharma KG; US6087380; (2000); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

178312-47-5, 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. 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, A new synthetic method of this compound is introduced below.

.4.4-Difluorocyclohexanecarbaldehvde; )-Propylmagnesium chloride (20 mL of a 2.0 M solution in THF, 40 mmol) was added dropwise to a oled (-150C) suspension of ethyl-4,4-difluorocyclohexanecarboxylate (3.0 g, 15.6 mmol) and N1O- nethylhydroxylamine hydrochloride (2.28 g, 23.4 mmol) in THF (30 mL). The reaction mixture was rred for 15 min then quenched with satd. NuH4Cl(aq). The product was extracted into ethyl acetate 2). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated to give i-difluoro-iV-methoxy-N-methylcyclohexanecarboxamide as a clear oil (3.01 g, 93% yield). ? a solution of the aforementioned Wei?reb amide (3.0 g, 14.5 mmol) in diethyl ether (30 mL) at -780C is added, dropwise, diisobutylaluminium hydride (16 mL of a 1.0 M solution in toluene).On mpletion of addition, the mixture was stirred for a further 15 min before being poured into a stirred xture of diethyl ether (50 mL), hexanes (50 mL) and IN HCl(aq) (100 mL). The mixture was stirred r 5 rnins and then the layers were separated and the organic phase dried (MgSO4) and concentrated to /e 4)4-difluorocyclohexanecarboxaldehyde.

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; MERCK SHARP & DOHME LIMITED; WO2006/134341; (2006); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 1186-73-8, name is Trimethyl methanetricarboxylate, A new synthetic method of this compound is introduced below., 1186-73-8

Step 6; methyl 10-(((tert-butyldimethylsilyl)oxy)methyl)-l-(2,4-dimethoxybenzyl)-4- hydroxy-9-methyl-2-oxo-l,2,5,6,7,9-hexahydropyrido[3′,2′:6,7]cyclohepta[l,2- f] indole-3-carboxylate Crude N-(2-((tert-butyldimethylsilyloxy)methyl)-l-methyl-6,7,8,9- tetrahydrocyclohepta[fJindol-5(lH)-ylidene)-l-(2,4-dimethoxyphenyl)methanamine (10.6 g, 20.91 mmol) and trimethyl methanetricarboxylate (6.80 g, 35.76 mmol) were mixed together in PI12O (40 mL). With stirring, the mixture was placed onto a pre-heated heat block at 230 C and heated for 10 min after the initial bubbling of MeOH was observed (occurs at -160 C internal reaction temperature). The reaction mixture was cooled to room temperature, then purified by column chromatography (hexanes followed by EtOAc/hexanes 0-80% gradient) to yield the product as a yellow foam (7.44 g, 56%, 2 steps). XH NMR (500 MHz, CHCl3-i/) delta ppm 0.08 (s, 3 H) 0.09 (s, 3 H) 0.90 (s, 9 H) 1.45 – 1.55 (m, 1 H) 1.85 – 1.95 (m, 1 H) 1.96 – 2.05 (m, 1 H) 2.32 – 2.44 (m, 1 H) 2.58 (dd, J=13.4, 6.1 Hz, 1 H) 2.96 (dd, J=13.4, 5.4 Hz, 1 H) 3.33 (s, 3 H) 3.76 (s, 3 H) 3.78 (s, 3 H) 4.00 (s, 3 H) 4.80 (s, 2 H) 5.13 – 5.37 (m, 2 H) 6.22 (d, J=2.2 Hz, 1 H) 6.28 (s, 1 H) 6.34 (dd, J=8.4, 2.2 Hz, 1 H) 6.81 (d, J=8.4 Hz, 1 H) 7.06 (s, 1 H) 7.32 (s, 1 H) 13.66 (br. s, 1 H). LC-MS 633.5 [M+H]+, RT 1.85 min.

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; 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

Adding a certain compound to certain chemical reactions, such as: 23877-12-5, name is tert-Butyl 2-bromo-2-methylpropanoate, 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 23877-12-5, 23877-12-5

4-Hydroxybenzaldehyde (1) (5 g, 40.9 mmol) commercially available from Sigma-Aldrich was dissolved in N, N-dimethylformamide (50 mL) and potassium carbonate ), Magnesium sulfate (1.0 eq) and Tert-Butyl-a-bromoisobutyrate (5.0 eq) (R = -CH 3) were added in this order, and the mixture was stirred at 100 C for 22 hours. The reaction mixture was diluted with water and then extracted with ethyl acetate. The organic solvent layer was dried by adding anhydrous sodium sulfate, filtered, distilled, and purified by flash column chromatography to obtain the compound 2a (R = -CH3).

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, tert-Butyl 2-bromo-2-methylpropanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Seoul National University R&DB Foundation; PARK, SEUNG-BUM; KOH, MIN-SEOB; KOO, JA-YOUNG; (32 pag.)KR101727634; (2017); B1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics