Tag: M.W=100-200

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. 3618-04-0, name is trans-Ethyl 4-hydroxycyclohexanecarboxylate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Formula: C9H16O3

To a solution of ethyl 4-hydroxycyclohexanecarboxylate 2 (mixture of cis and trans) (2.5 g, 14.5 mmol) and imidazole (1.97 g, 29 mmol) in anhydrous DMF (20 mL), tert-butyldimethylsilyl chloride (2.63 g, 17.5 mmol) was added. After stirring overnight, Et2O (60 mL) and 1M aqueous HCl (60 mL) were added. After extraction with Et2O, the combined organic phases were washed with 1M aqueous HCl and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a TBS-protected alcohol as a colorless oil (4.14 g), which was used in the next step without further purification. To a solution of the former alcohol (4.14 g, 14.5 mmol) in THF (20 mL) and methanol (12 mL), lithium hydroxide (0.7 g, 29 mmol) was added. The mixture was then stirred at 60 C for 3 h. After removal of the solvents, water and Et2O were added and the aqueous layer was extracted with diethyl ether, cooled in an ice bath then acidified to pH=1 with 1M aqueous HCl. After extraction with ethyl acetate, the organic phases were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 50:50) to give the title compound 3 as a mixture of cis/trans isomers (3.48 g, 100% yield) as a colorless oil; deltaH (400 MHz, CDCl3) 10.84 (2H, m, 2*COOH), 3.89 and 3.56 (2*1H, 2*bs, 2*H-4), 2.41-2.18 (2H, m, 2*H-1), 2.10-1.83 (6H, m), 1.74-1.59 (4H, m), 1.58-1.23 (6H, m), 0.88 and 0.87 (2*9H, 2*s, 2*(CH3)3CSi), 0.05 and 0.03 (2*6H, 2*s, 2*(CH3)2Si); deltaC (100 MHz; CDCl3) 181.8 (2*COOH), 70.5 and 66.7 (2*C-4), 42.0 and 41.9 (2*C-1), 34.8 (2*CH2), 32.9 (2*CH2), 27.1 (2*CH2), 23.4 (2*CH2), 26.1 and 26.0 (2*(CH3)3CSi), 18.3 and 18.2 (2*(CH3)3CSi), -4.5 and -4.7 (2*(CH3)2Si).

The synthetic route of 3618-04-0 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zeinyeh, Wael; Radix, Sylvie; Terreux, Raphael; Chemelle, Julie-Anne; Walchshofer, Nadia; Tetrahedron; vol. 72; 27-28; (2016); p. 4032 – 4038;,
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Synthetic Route of 46004-37-9, 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. 46004-37-9, name is Methyl 4-amino-2-chlorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

2-chloro-4-aminobenzoic acid, methyl ester (13.95 g) was suspended in a mixture of water (65 ml) and concentrated hydrochloric acid (15.7 ml). After stirring at room temperature for 10 minutes, the suspension was cooled to 0 C. A solution of sodium nitrite (5.71 g) in water (37 ml) was gradually added over 20 minutes, maintaining a reaction temperature of 0 C. After stirring at 0 C. for 35 minutes, the reaction mixture was partially neutralized by the addition of solid sodium carbonate (3.16 g) to afford a cold solution of the diazonium salt.

The synthetic route of Methyl 4-amino-2-chlorobenzoate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; American Cyanamid Company; US6831079; (2004); 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. 53088-68-9, name is Methyl (3-Chlorophenyl)acetate, A new synthetic method of this compound is introduced below., SDS of cas: 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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Application 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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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. 924-99-2, name is Ethyl 3-(dimethylamino)acrylate, A new synthetic method of this compound is introduced below., Safety of Ethyl 3-(dimethylamino)acrylate

General procedure: All microwave reactions were carried out in a capped (10 mL) microwave-vessel (Borosilicate glass vial sealed) that was placed in a microwave cavity. The pressure was set at 17 bar (average of an effective pressure = 4 bar) with power 75 W. DIEA (3.4 g, 3.4 mmol) was added to a solution of either 2,5-difluoro-4-(pyrrolidin-1-yl) benzoylchloride 12 (0.83 g, 3.4 mmol) or 2,5-difluoro-4-(pyrrolidin-1-yl)benzothioyl chloride 13 (0.88 g, 3.4 mmol) and ethyl-3-(diethylamino)acrylate 14 (0.45 g, 3.1 mmol) in acetonitrile (5 mL). The mixture reaction was held at 100 C for 20 min. After the reaction vessel was cooled to room temperature, the crude product was diluted with water (10 mL) and extracted with ethyl acetate(3 × 10 mL). The organic layers were combined, dried over Na2SO4, filtered, evaporated and purified by a flash column chromatography (eluent n-hexane: acetone, 3:1)to give the titled compounds. Ethyl-2-(2,5-difluoro-4-(pyrrolidin-1-yl)benzoyl)-3-(dimethylamino) acrylate (15)Yellow oil (Rf = 0.3), Yield 85%. IR (KBr) numax in cm-1:2993 (C-H, Ar), 2953 (C-H), 1760 (C=O), 1692 (C=O),1654 (C=C, Ar), 1592 (C-N). 1H NMR (400 MHz, DMSOd6):delta = 7.77 (1H, s, CH), 7.32 (1H, d, J = 5.0 Hz, CH-Ar),6.88 (1H, d, J = 5.2 Hz, CH-Ar), 4.2 (2H, q, J = 7.1 Hz,CH2), 3.47-3.42 (4H, m, 2CH2), 3.1 (6H, s, 2CH3), 2.01-1.97 (4H, m, 2CH2), 1.32 (3H, t, J = 4.2 Hz, CH3).

The synthetic route of 924-99-2 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Almashal, Faeza A.; Alshawi, Jasim M.; Dhumad, Adil M.; Jassem, Ahmed M.; Medicinal Chemistry Research; (2020);,
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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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Electric Literature 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.

A mixture of (3-chloro-quinolin-6-yl)-acetic acid hydrazide (4.0 g, 16.97 mmol, 1.0 eq) and ethoxy-imino-acetic acid ethyl ester (4.9 g, 33.95 mmol, 2.0 eq) in EtOH (200 mL) and AcOH (10 mL) was stirred at rt for 30 min, and then concentrated. The resulting residue was dried in vacuo to afford amino-{[2-(3-chloro-quinolin-6-yl)-acetyl]-hydrazono}-acetic acid ethyl ester (5.0 g, 89%) as a white solid.

The synthetic route of 816-27-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; QIAN, Shawn; (183 pag.)WO2019/142053; (2019); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 29006-01-7, name is Methyl 4-methoxybutanoate, molecular formula is C6H12O3, 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. Product Details of 29006-01-7

The toluenic solution obtained in A) (4.00 Kg of 4-trifluoromethylbenzylamine) was charged in a reactor. After distillation until an oil residue was obtained, 3.20 Kg of methyl 4-methoxybutyrate, 0.40 kg of 30% sodium methylate were added. The solution was then heated to 1 10-1200C, distilling at atmospheric pressure in order to remove all methanol (also methanol freeing from the reaction) and maintaining such temperature for at lest two hours. The reactor at 1 10-120C was then put under vacuum for at least one hour. At the end of the reaction, 12.0 Kg of toluene, 2.0 Kg of water and 0.40 Kg of 80% acetic acid were added to the mass. After stirring, the lower aqueous phase was separated and removed. The organic phase was then distilled under vacuum to a oil residue. To such a residue, 4.00 Kg of ethylacetate, 12.0 Kg of n-hexane were added and the final mass was heated to 40-60 C until a complete solution was obtained. Then the solution was brought to 20-30 C and so maintained until a good precipitation was obtained. The mass was then cooled to 0C – 10C, centrifuged by washing with a mixture of 0.80 Kg of ethylacetate, 4.00 Kg of n-hexane. The obtained humid product was used as such in the following step.About 3.8 Kg of crude N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide were obtained. Yield: 60.5%

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 29006-01-7, its application will become more common.

Reference:
Patent; LABORATORIO FARMACEUTICO C.T. S.R.L.; WO2009/62949; (2009); A1;,
Ester – Wikipedia,
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2065-23-8, name is Methyl 2-phenoxyacetate, 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. name: Methyl 2-phenoxyacetate

To a solution of 55 mg (1.00 mmol) of propargyl amine (2), in dry MTBE (2 mL) in a screwcapSchlenk vessel, were added 1.5 mmol of the methyl ester 1 (for experimental details seeTable 1) and Novozyme 435 (50 % w/w of corresponding ester substrate used) and thereaction was shaken in an incubating shaker at 45 C for 4 or 24 h (depending upon the natureof ester used). After the reaction time, the enzyme beads were filtered off and the filtrate wassubjected to column chromatography on silica gel (n-hexane/ethylacetate 1:1 or 2:1) to obtainthe pure product 3.

The synthetic route of 2065-23-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Hassan, Sidra; Tschersich, Roxanne; Mueller, Thomas J.J.; Tetrahedron Letters; vol. 54; 35; (2013); p. 4641 – 4644;,
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349-43-9, A common heterocyclic compound, 349-43-9, name is Ethyl 2-fluoropropionate, molecular formula is C5H9FO2, 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.

LDA (2.0 M, 36 mL) was added to the solution of ethyl 2- fluoropropanate (7.23 g) and acetaldehyde (13.5 mL) in ether (100 mL) at-78 °C. After the addition finished the reaction flask was kept in ice bath and gradually warm to room temperature. The reaction was quenched with aqueous ammonium chloride after overnight stirring. The aqueous phase was extracted with ether and the combined organic phase was dried over sodium sulfate. The solvent was stripped off and the residue was distilled in vacuo to give 541-YJ-97 (4.22 g).

The synthetic route of 349-43-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; EISAI CO. LTD.; WO2003/76424; (2003); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics