Category: esters-buliding-blocks

Synthetic Route of 816-27-3,Some common heterocyclic compound, 816-27-3, name is Ethyl 2-ethoxy-2-iminoacetate, molecular formula is C6H11NO3, 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.

Sodium hydride (60% in oil, 0.390 g, 9.7 mmol) was added to a solution of 3-[tert- butyl(dimethyl)silyl]oxy-5-(3-fluoro-2-pyridyl)pyrrolidin-2-one (2.0 g, 6.4 mmol) in N,N- dimethylformamide (64 mL) at 0C. After 30 min, O-diphenylphosphorylhydroxylamine (2.3 g, 9.7 mmol) was added. The reaction was warmed to rt and stirred for 16h. The reaction was filtered and the filtrate was evaporated under reduced pressure. The crude residue was submitted to the next reaction without further purification. LCMS RT = 1.34 min, m/z = 326.0 [M + H]+ and LCMS RT = 1.30 min, m/z = 326.0 [M + H]+. Ethyl 2-ethoxy-2-iminoacetate (2.50 g, 16 mmol) and the crude residue were dissolved in ethanol (23 mL) and the reaction was heated at 90C for 16h. After cooling to rt, the reaction was filtered and the filtrate was concentrated under reduced pressure. The crude residue was submitted to the next reaction without further purification. LCMS RT = 1.38 min, m/z = 425.0 [M + H]+ and LCMS RT = 1.34 min, m/z = 425.0 [M + H]+. p-Toluenesulfonic acid monohydrate (1.5 g, 7.7 mmol) was added to a solution of the crude residue in toluene (25 mL). The reaction was heated at 120C for 16 h. After cooling to rt the reaction was filtered and the filtrate was concentrated under reduced pressure. The crude residue was submitted to the next reaction without further purification. LCMS RT = 1.55 min, m/z = 407.0 [M + H]+ and LCMS RT = 1.50 min, m/z = 407.1 [M + H]+. Tetrabutylammonium fluoride (1.0 M in THF, 6.4 mL, 6.4 mmol) was added to a solution of the crude residue in THF (21 mL) and the reaction was heated at 40C for 1 h. After cooling to rt saturated aqueous ammonium chloride was added. The aqueous layer was extracted with isopropyl acetate (4 x 50 mL). The combined organic layers were dried over sodium sulfate, concentrated and the crude residue was purified by flash column chromatography (silica 0% to 10% methanol/ dichloromethane) to give ethyl 5-(3-fluoro-2-pyridyl)-7-hydroxy-6,7-dihydro-5H- pyrrolo[l ,2-b] [l ,2,4]triazole-2-carboxylate (0.800 g, 2.74 mmol, 42% yield). NMR (400 MHz, Chloroform-if) 1 : 1 mixture of diastereomers delta 8.41 – 8.29 (m, 1H), 7.63 – 7.26 (m, 2H), 6.12 (dd, J = 8.1 , 4.4 Hz, 0.5H), 6.07 (d, J = 8.2 Hz, 0.5H), 5.64 (dd, J = 7.6, 4.0 Hz, 0.5H), 5.21 (d, J = 6.5 Hz, 0.5H), 4.51 – 4.38 (m, 2H), 3.45 (ddd, J = 14.7, 8.3, 6.6 Hz, 0.5H), 3.29 (ddd, J = 13.8, 7.5, 4.3 Hz, 0.5H), 3.10 (ddd, J = 13.8, 8.1 , 4.0 Hz, 0.5H), 2.74 (d, J = 14.4 Hz, 0.5H), 1.40 (t, J = 7.1 Hz, 3H). LCMS RT = 0.89 min, m/z = 292.9 [M + H]

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; PATEL, Snahel; HAMILTON, Gregory; ZHAO, Guiling; CHEN, Huifen; DANIELS, Blake; STIVALA, Craig; (358 pag.)WO2019/12063; (2019); A1;,
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Reference of 82702-31-6, 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. 82702-31-6, name is Methyl 3-bromo-4-fluorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A solution of methyl 3-bromo-4-fluorobenzoate (4.22 g, 18.10 mmol) and Example 1g (2.727 g, 19.46 mmol) in dimethyl sulfoxide (18.10 mL) was treated with cesium carbonate (9.28 g, 28.5 mmol) . The reaction mixture was heated at about 80 C for about 2 hours and cooled to ambient temperature. Water (50 mL) was added, and the reaction mixture was stirred for 10 minutes. The reaction mixture was extracted with methyl tert-butyl ether (1x 100 mL, then 2×50 mL) . The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 100% heptanes to 30ethyl acetate: heptanes) to provide the title compound as a white solid (5.29 g, 15.0 mmol, 83% yield) .

The synthetic route of Methyl 3-bromo-4-fluorobenzoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ABBVIE INC.; ABBVIE PHARMACEUTICAL TRADING (SHANGHAI) CO., LTD.; COWART, Marlon; FIDANZE, Steven; HASVOLD, Lisa; LIU, Dachun; MCDANIEL, Keith; PRATT, John; SHEPPARD, George; WANG, Le; (241 pag.)WO2018/68283; (2018); A1;,
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Synthetic Route of 18595-18-1, 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. 18595-18-1, name is Methyl 3-amino-4-methylbenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Triethylamine (0.12 g, 1.12 mmol) was added to a mixture of crude 2-methoxy-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid (0.22 g, 1 mmol) (from Example 18 supra) and HATU (0.43 g, 1.12 mmol) (Aldrich) in DMF (10 mL) at room temperature. Mixture was stirred until clear solution was obtained (light brown). 3-Amino-p-toluic acid methyl ester (0.2 g, 1.2 mmol) (TCI-US) was added. Mixture was stirred for another 18 hours. Precipitate was formed. Water (45 mL), saturated aqueous sodium bicarbonate solution (5 mL), and ethyl acetate (20 mL) were added. After thorough mixing, yellow precipitate was collected by filtration, washed with water and ethyl acetate and dried in vacuum oven. (Yield 0.25 g, 67.9%). Sample was recrystallized from DMF with trace amounts of water to give 3-[(2-methoxy-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonyl)-amino]-4-methyl-benzoic acid methyl ester as pale yellow crystals that contained trace amounts of DMF. (Yield 0.23 g, 62%).LR-LC/MS (APCi+) m/z [M+H]+ 369.

The synthetic route of Methyl 3-amino-4-methylbenzoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Anderson, Kevin; Chen, Yi; Chen, Zhi; Luk, Kin-Chun; Rossman, Pamela Loreen; Sun, Hongmao; Wovkulich, Peter Michael; US2012/184542; (2012); A1;,
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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. 53088-68-9, name is Methyl (3-Chlorophenyl)acetate, A new synthetic method of this compound is introduced below., Product Details of 53088-68-9

To a stirred mixture of methyl 3-clorophenylacetate (25.4 g, 128 mmol) in H2SO4 (44 ml) was added HNO3 (5.5 ml, 138 mmol) at 0 C. The reaction mixture was gradually raised to room temperature for 4 h. The reaction mixture was poured into ice water and extracted with EtOAc. The combined extracts were washed with aq. NaHCO3 and brine. After dried over Na2SO4, the extracts were concentrated in vacuo. The residue was chromatographed on silica gel [1 kg, n-hexane/EtOAc (40/1)] to give methyl 3-chloro-4-nitrophenylacetate (11.4 g, 36%) as a yellow oil. 1H-NM (CDCl3) delta 3.69 (s, 2H), 3.74 (s, 3H), 7.33 (dd, J=8.3, 1.5 Hz, 1H), 7.49 (d, J=1.5 Hz, 1H), 7.87 (d, J=8.3 Hz, 1H).

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; Daiichi Pharmaceutical Co., LTD.; US2003/78249; (2003); A1;,
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Adding a certain compound to certain chemical reactions, such as: 69812-51-7, name is Methyl 4-chlorosulfonylbenzoate, 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 69812-51-7, Product Details of 69812-51-7

General procedure: To a solution of 23 (313 mg, 1 mmol) in DMF (1 mL), was addedtriethylamine (210 mg, 2.05 mmol), methyl 4-chlorosulfonyl benzoate27c (235 mg, 1 mmol) and 4-dimethylaminopyridine (10 mg). Themixture was stirred at rt for 4 h. The solvent was removed and the residuewas purified by a silica column with CHCl3 and MeOH to afford356 mg of 24f as a white solid in 75% yield. TLC Rf 0.13 (CHCl3/MeOH,40:1); 1H NMR (DMSO-d6) delta 1.25 (s, 9H, Piv), 2.61 (s, 3H, NCH3), 3.91(s, 3H, OCH3), 4.21 (s, 2H, NCH2), 6.28 (s, 1H, 5-H), 7.95 (d,J=8.0 Hz, 2H, Ph), 8.18 (d, J=8.0 Hz, 2H, Ph), 10.85 (s, 1H, exch,PivNH), 11.66 (s, 1H, exch, NH), 11.88 (s, 1H, exch, NH).

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:
Article; Xiang, Weiguo; Dekhne, Aamod; Doshi, Arpit; O’Connor, Carrie; Hou, Zhanjun; Matherly, Larry H.; Gangjee, Aleem; Bioorganic and Medicinal Chemistry; vol. 27; 23; (2019);,
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Adding a certain compound to certain chemical reactions, such as: 13831-03-3, name is tert-Butyl propiolate, 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 13831-03-3, name: tert-Butyl propiolate

n-Butyllithium (1.6 M in hexane; 41.9 mL, 67.0 mmol) was added dropwise within 10mm at -55 to -50CC to a soln of tert-butyl propiolate (103; 8.76 mL, 63.8 mmol) in dryTHF (200 mL). The mixture was allowed to stir at -40C for 1.5 h. The mixture wascooled to -78C. A soln of 102 (7.25 g, 31 9 mmol) in THF (66 mL) was added within 10 mm with the temperature not exceeding -64C. The mixture was stirred for 0.5 h at-78C, then warmed to -40C and allowed to slowly warm to 0C over 3 h. The mixture was poured into 1 M aq. KHSO4 soln and extracted with EtOAc. The organicphase was dried (Na2SO4) and concentrated. FC (hexane/EtOAc 90:10 to 70:30) afforded the ketone 104 (8.34 g, 89%).

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

Reference:
Patent; POLYPHOR AG; OBRECHT, Daniel; ERMERT, Philipp; OUMOUCH, Said; PIETTRE, Arnaud; GOSALBES, Jean-Francois; THOMMEN, Marc; WO2013/139697; (2013); A1;,
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63485-50-7, name is cis-Methyl 3-hydroxycyclobutanecarboxylate, 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. Product Details of 63485-50-7

Triphenylphosphine (484 mg, 1 .85 mmol) was added to a solution of 2,5-difluorophenol (0.2 g, 1 .537 mmol) in tetrahydrofuran (1 .7 mL). The reaction mixture was cooled to 0 C, and (c/s)-methyl 3-hydroxycyclobutanecarboxylate (240 mg, 1 .85 mmol) was added, followed by DIAD (0.35 mL, 1 .8 mmol). After 10 min, the reaction mixture was warmed to room temperature, stirred for 3 days, and diluted with water and EtOAc. The mixture was partitioned, and the aqueous layer was extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate, filtered, and concentrated. The residue was purified on silica gel eluting with a 10%-60% EtOAc-heptane gradient to give the title compound (236 mg, 63%). 1H NMR (400 MHz, CDCI3) delta 2.48-2.59 (m, 2 H), 2.76 (ddd, J = 14, 7, 4 Hz, 2 H), 3.16-3.26 (m, 1 H), 3.75 (s, 3 H), 4.90 (quin, J = 7 Hz, 1 H), 6.49-6.63 (m, 2 H), 7.02 (ddd, J = 10, 9, 5 Hz, 1 H); LC-MS (LC-ES) M+H = 243.

The synthetic route of 63485-50-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; DEATON, David Norman; GUO, Yu; HANCOCK, Ashley Paul; SCHULTE, Christie; SHEARER, Barry George; SMITH, Emilie Despagnet; STEWART, Eugene L.; THOMSON, Stephen Andrew; (556 pag.)WO2018/69863; (2018); A1;,
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Synthetic Route of 1132-95-2, 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 1132-95-2 as follows.

The compound (103 mg) produced in production step 11-1 was dissolved in 2.0 mL of N,N-dimethylformamide. Cyclohexanone di-i-propyl acetal (58 muL) and 12.4 mg of p-toluenesulfonic acid were added to the solution, and the mixture was allowed to react at room temperature for one hr. A saturated aqueous sodium bicarbonate solution (20 mL) was added thereto, and the resultant precipitate was collected by filtration, was washed with water, and was dried under the reduced pressure to give the title compound (103 mg, 88%). Rf value: 0.53 (chloroform: methanol = 10: 1) ESIMS: m/z 1171 [M + Na]+

According to the analysis of related databases, 1132-95-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Meiji Seika Kaisha Ltd.; Microbial Chemistry Research Foundation; EP2036917; (2009); A1;,
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Related Products of 5445-17-0, 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. 5445-17-0, name is Methyl 2-bromopropanoate, This compound has unique chemical properties. The synthetic route is as follows.

Example 7 methyl 2-(2-(pyrrolidin-1-yl)cyclohex-2-en-1-yl)propanoate To a 1 L round bottom flask was added 1-(cyclohex-1-en-1-yl)pyrrolidine (100 g, example 1), acetonitrile (800 mL), methyl 2-bromopropanoate (116.3 g), and sodium iodide (9.9 g). The mixture was then heated to reflux while stirring for 20 hours. The mixture was cooled to room temperature, added DBU (100.3 g), and stirred for 30 minutes. The resulted mixture was then concentrated to remove most acetonitrile, followed by addition of toluene (500 mL). The suspension was stirred at room temperature for 1 hour followed by filtration. The filter cake was washed with small amount of toluene twice. The combined toluene solution was distilled under vacuum to give a liquid product, 143.4 g (91.4%). 1HNMR (CDCl3): delta 4.64 (t, 1H), 3.60 (s, 3H), 2.99 (q, 2H), 2.73 (m, 2H), 2.56 (m, 2H), 2.05 (m, 1H), 1.97 (m, 1H), 1.73 (m, 5H), 1.54 (m, 3H), 1.01 (d, 3H).

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

Reference:
Patent; Yi, Lin; Su, Xiping; Werth, Peter; (16 pag.)US2016/326113; (2016); A1;,
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Application of 56741-34-5, 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. 56741-34-5, name is Methyl 5-amino-2-fluorobenzoate, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: To a solution of compound 11a (154 mg, 1.0 mmol) in anhydrous CH2Cl2 (10 mL) was added 3,5-dichlorobenzoyl chloride (209 mg, 1.0 mmol) and pyridine (241 mL 3.0 mmol) under ice bath. After stirring at room temperature for about 8 h, the solvent was removed in vacuum. The resulting residue was dissolved in NaOH (1 M) water solution (3 mL) and CH3OH (3 mL) and stirred for another 2 h. Then the solvent was removed under vacuum, and the residue was acidied to pH 2 or below with HCl (1 M) water solution. The solution was extracted with ethyl acetate twice and the combined organics were dried over anhydrous sodium sulfate and concentrated in vacuum. The resulting residue was puried by silica gel chromatography to give the desired compound as a white solid (234 mg, yield 85.0%)

The chemical industry reduces the impact on the environment during synthesis Methyl 5-amino-2-fluorobenzoate. I believe this compound will play a more active role in future production and life.

Reference:
Article; Gao, Ding-Ding; Dou, Hui-Xia; Su, Hai-Xia; Zhang, Ming-Ming; Wang, Ting; Liu, Qiu-Feng; Cai, Hai-Yan; Ding, Hai-Peng; Yang, Zhuo; Zhu, Wei-Liang; Xu, Ye-Chun; Wang, He-Yao; Li, Ying-Xia; European Journal of Medicinal Chemistry; vol. 154; (2018); p. 44 – 59;,
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