Month: June 2021

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. 20637-08-5, name is Methyl 4-(4-methoxyphenyl)butanoate, A new synthetic method of this compound is introduced below., Product Details of 20637-08-5

a) 5-(4-Methoxyphenyl)-1-(3-pyridinyl)-2-pentanone A solution of n-butyl lithium (28 ml of 1.6M in hexane, 0.124 mol) was added to a stirred solution of diisopropylamine (4.55 g, 0.045 mol) in dry tetrahydrofuran (50 ml) at 0C under a nitrogen atmosphere and the resulting yellow solution was stirred at 0C for 30 minutes. To the solution was added hexamethylphosphoramide (8.06g, 0.045 mol) and the resulting solution was stirred at 0C for 15 minutes. 3-Picoline (4.19g, 0.045 mol) was added to the reaction mixture and the resulting deep-red solution was stirred at 0C for 30 minutes. To the solution was added 4-(4-methoxyphenyl)butyric acid methyl ester (9.36g, 0.045 mol) in dry tetrahydrofuran (20 ml). The resulting mixture was stirred at 0C for 15 minutes and then at room temperature for an additional 90 minutes. The pale-yellow solution was extracted with hydrochloric acid (300 ml of 1M). The acid solution was washed with ethyl acetate (2 * 250 ml), made basic using potassium hydroxide and extracted with ethyl acetate (4 * 200 ml). The combined extracts were dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product. The crude product was purified by column chromatography (silica gel, chloroform) and recrystallized from ethyl acetate-hexane to yield 5-(4-methoxyphenyl)-1-(3-pyridinyl)-2-pentanone as a colorless crystalline solid, having a melting point of 35-37C and the following physical characteristics: Elemental analysis: C,75.31%, H,7.03%, N,5.11%; as against calculated values of C,75.31%; %,7.14%, N,5.17% for C17H19NO2·0.1H2O. 1H-NMR (delta-CDCl3): 1.82-1.98 (m,2H), 2.46-2.62 (m,2H), 2.53 (t,2H), 3.67 (s,2H), 3.79 (s,3H), 6.83 and 7.06 (ABq,4H), 7.23-7.31 (m,1H), 7.29-7.37 (m,1H), 8.39-8.46 (m,1H) and 8.50-8.56 (m,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; G.D. Searle & Co.; EP267439; (1988); A3;,
Ester – Wikipedia,
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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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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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Ester – an overview | ScienceDirect Topics

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);,
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. 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;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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;,
Ester – Wikipedia,
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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;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 23062-51-3, name is Methyl 4-bromobicyclo[2.2.2]octane-1-carboxylate, molecular formula is C10H15BrO2, 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. Computed Properties of C10H15BrO2

Methyl 4- bromobicyclo [2.2.2]octane-l-carboxylate (17.0 g, 69.0 mol) was refluxed in aqueous sodium hydroxide solution (1500 mL, 1 %) for 24 h. After cooling, the reaction solution was acidified with hydrochloric acid (6 N, 100 mL) and extracted with diethyl ether (6 x 500 mL). The combined ether layers were dried over magnesium sulfate and concentrated to afford the title compound (10.4 g, 61.1 mmol, 89 % yield), which was used in the next step without further purification. MS (ESI) m/z 169.2 [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 23062-51-3, its application will become more common.

Reference:
Patent; SIGNAL PHARMACEUTICALS, LLC; BENNETT, Brydon, L.; ELSNER, Jan; ERDMAN, Paul; HILGRAF, Robert; LEBRUN, Laurie, Ann; MCCARRICK, Meg; MOGHADDAM, Mehran, F.; NAGY, Mark, A.; NORRIS, Stephen; PAISNER, David, A.; SLOSS, Marianne; ROMANOW, William, J.; SATOH, Yoshitaka; TIKHE, Jayashree; YOON, Won, Hyung; DELGADO, Mercedes; WO2012/145569; (2012); A1;,
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Application of 5445-17-0, The chemical industry reduces the impact on the environment during synthesis 5445-17-0, name is Methyl 2-bromopropanoate, I believe this compound will play a more active role in future production and life.

Methyl 2-bromopropanoate (1.0 eq, 10 g, 59.9 mmol) and triethylphosphite (5.0 eq, 299.5 mmol, 51.5 mL) were combined neat and heated to 110 C. with stirring overnight. The reaction mixture was concentrated, azeotroped with toluene 3×, and dried under high vacuum. The resulting phosphonate was obtained in quantitative yield and was used directly in the following reaction: The phosphonate (1.0 eq, 10.0 g, 44.6 mmol) was dissolved in anhydrous THF (100 mL) and cooled to 0 C. To this mixture, n-BuLi (2.5 M in Hexanes, 18.7 mL, 46.8 mmol, 1.05 eq) was added drop wise. The mixture was stirred for 2 hours at 0 C., then cyclohexanone (1.0 eq, 44.6 mmol, 4.6 mL) was added. The mixture was stirred at 0 C. gradually warming to ambient temperature over 72 hours. The reaction was quenched with saturated aqueous ammonium chloride (500 mL) and concentrated. The remaining aqueous layer was extracted with ethyl acetate (2×200 mL) to give 16.8 g of the crude ester as a yellow oil which was purified by flash column chromatography (hex/ethyl acetate gradient). 3.7 g of a pale yellow oil was obtained as mixture of methyl and ethyl esters in about 1.4:1 molar ratio (21.25 mmol, 48% yield). The isolated mixed ester (3.2 g, 18.36 mmol) was dissolved in ethanol (50 mL) and solid sodium hydroxide (1.0 g, 25 mmol) was added. The mixture was refluxed until reaction was complete. Ethanol was subsequently removed and the residue was partitioned between ethyl acetate (50 mL) and a 1.0 N solution of HCl (50 mL). The aqueous layer was acidified with 6.0 N HCl until acidic and extracted with ethyl acetate (50 mL) again. Combined organic layers were washed with brine and dried over magnesium sulfate. The crude material was purified by flash column chromatography (hex/ethyl acetate gradient) to afford 2.0 g (71% yield) of the desired isomer as a yellow oil in 90% purity by 1H-NMR. (0850) 1H NMR (400 MHz, DMSO-d6): delta, ppm: 12.18 (s, 1H), 2.40 (m, 2H), 2.17 (m, 2H), 1.77 (s, 3H), 1.52 (m, 6H).

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, Methyl 2-bromopropanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SENOMYX, INC.; Chumakova, Lyudmyla; Patron, Andrew; Priest, Chad; Karanewsky, Donald; Kimmich, Rachel; Boren, Brant Clayton; Hammaker, Jeffrey Robert; Chumakov, Volodymyr; Zhao, Wen; Noncovich, Alain; Ung, Jane; (146 pag.)US2015/376136; (2015); A1;,
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