Month: October 2020

3196-15-4, name is Methyl 2-bromobutyrate, 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. 3196-15-4

1.80 g (9.66 mmol) of tert-butyl 2-(aminomethyl)azetidine-1-carboxylate [racemate] were dissolved in 25 ml of dichloromethane, 1.62 ml (1.17 g, 11.6 mmol) of triethylamine and 1.11 ml (1.75 g, 9.66 mmol) of methyl 2-bromobutanoate [racemate] were added and the mixture was stirred under reflux overnight. 1.35 ml (0.98 g, 9.66 mmol) of triethylamine and 0.89 ml (1.40 g, 7.73 mmol) of methyl 2-bromobutanoate [racemate] were then added, and the mixture was stirred under reflux overnight. After cooling to room temperature, water was added and the phases were separated. The aqueous phase was extracted twice with dichloromethane and the combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and then freed of the solvent under reduced pressure. This gave 2.64 g (83% of theory, purity: 87%) of the desired product. LC-MS (Method 6A): Rt=2.16 min (diastereomer 1, 2 isomers), Rt=2.22 min (diastereomer 2, 2 isomers); MS (ESIpos): m/z=287 [M+H]+

Statistics shows that 3196-15-4 is playing an increasingly important role. we look forward to future research findings about Methyl 2-bromobutyrate.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; ALLERHEILlGEN, Swen; BUCHMUeLLER, Anja; ENGEL, Karen; GERDES, Christoph; GERICKE, Kersten Matthias; GERISCH, Michael; HEITMEIER, Stefan; HILLlSCH, Alexander; KINZEL, Tom; LIENAU, Philip; RIEDL, Bernd; ROeHRIG, Susanne; SCHMIDT, Martina Victoria; STRASSBURGER, Julia; TERSTEEGEN, Adrian; (135 pag.)US2016/108027; (2016); A1;,
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34846-90-7, Adding a certain compound to certain chemical reactions, such as: 34846-90-7, name is Methyl 3-methoxyacrylate, 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 34846-90-7.

Under nitrogen protection, add 12.9g (323.5mmol) of NaH and 150g of DMF to the reaction flask at -15-10¡ãC.4-amino-1,1,1-trifluoro-3-buten-2-one50 g (359.5 mmol) solution, the system turned from colorless to light yellow and finally to a red suspension,Methyl 3-methoxyacrylate (41.75 g, 359.5 mmol) was added dropwise and reacted at this temperature for 3 hours.Concentrated hydrochloric acid was added dropwise to the reaction flask at -10¡ãC to adjust the pH of 8-9. The system changed from a deep red suspension to orange, and water was added.1.5L of dilute hydrochloric acid was used to adjust the pH to 1 to 2, and a large amount of white flocculent solids precipitated. After stirring for 0.5 hours, 81.5 g of a white product was obtained by filtration (yield, 88.3percent).The NMR analysis of the product obtained in this example is shown in Figure 1.Prove that the resulting product isN-1-methoxy-2-methoxycarbonylethyl-4,4,4-trifluoro-3-keto-1-butenamine..

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 3-methoxyacrylate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Shanghai Heteng Fine Chemical Co., Ltd.; Chen Sheng; Shi Guancheng; Meng Haicheng; (8 pag.)CN107628991; (2018); A;,
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Ester – an overview | ScienceDirect Topics

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. 23877-12-5, name is tert-Butyl 2-bromo-2-methylpropanoate, This compound has unique chemical properties. The synthetic route is as follows., 23877-12-5

Step 2: 1-[4-methylthiophenyl]-(E)-3-[3,5-dimethyl-4-tertiobutylcarbonyldimethylmethyloxyhenyl]prop-2-en-1-one (Intermediate 2) Caesium carbonate (87 g, 0.134 mol, 4 eq) and tetrabutylammonium iodide (12 g, 0.033 mol, 0.5 eq) are added to an intermediate solution 1 (20 g, 0.067 mol, 1 eq) in 50 ml of a DMSO/water mixture (3/2). The reaction medium is stirred for 30 minutes at 80 C. and tert-butyl bromoisobutyrate (30 g, 0.134 mol, 2 eq) is added. Then 2 additions of 2 eq of tert-butyl bromoisobutyrate diluted to 50% in DMSO are each made at an interval of 1 hour. The reaction medium is stirred for 2 days at 80 C. The reaction medium is left to cool to ambient temperature and then 1.5 litres of water are added and the product is extracted with dichloromethane (4 times). The organic phase is dried on a phase-separation cartridge and evaporated dry. Purification on silica gel (cyclohexane/ethylacetate: 95/5 to 80/20): 18 g (orange solid, yield: 61%).

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; NASHPHARM; LARUELLE, Claude; BONNAFOUS, Ludovic; US2020/23067; (2020); 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. 344-14-9, name is Dimethyl 2-fluoromalonate, A new synthetic method of this compound is introduced below., 344-14-9

Part A: 5-Fluoro-6-hydroxy-2-methylthio-4(1 H)-pyrimidinone To a stirred solution of 2-methyl-2-thiopseudourea sulfate (41.7 g, 0.15 mol) and dimethyl fluoromalonate (45 g, 0.30 mol) in MeOH (600 mL) at 0 C (ice bath) was added NaOMe (48.6 g, 0.90 mol) in portions. After the addition was complete, the ice bath was withdrawn and the reaction mixture was stirred at room temperature overnight. LCMS showed the formation of the desired pyrimidinone product. The reaction mixture was concentrated to near dryness under vacuum, diluted with water (50 mL), and acidified with 6N HCI (-150 mL) to ~pH 2 to precipitate the product. After filtration, the solid was washed with 1 N HCI (2 x 10 mL) and dried under vacuum to afford 5-fluoro-6- hydroxy-2-methylthio-4(1 H)-pyrimidinone (35.7 g, 68%) as a white solid. LCMS: (M+H)+: 177.3.

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; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO. 2) LIMITED; AUBART, Kelly, Marshall; GILLIAN, Jason, Michael; QIN, Donghui; MCKEOWN, Robert, Rahn; WILLIAMS, Glenn, R.; WO2013/82388; (2013); A1;,
Ester – Wikipedia,
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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. 110661-91-1 name is tert-Butyl 4-bromobutanoate, 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. 110661-91-1

Methyl 3-(4-(tert-butoxy)-4-oxobutoxy)beiizoate A solution of methyl 3Thydroxybenzoate (commercially available from for example Aldrich) (1 g, 6.6 mmol) and K2C03 (1.82 g, 13.2 mmol) in DMF (10 mL) was treated with tert-butyl 4-bromobutanoate (commercially available from for example Aldrich) (2.2 g, 9.9 mmol) and the mixture was stirred at 60 C for 16 hours. A further aliquot of K2C03 (1.82 g, 13.2 mmol) and tert-butyl 4-bromobutanoate (2.2 g, 9.9 mmol) were added and the mixture was heated at 60 C for further 6 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was washed with brine (2 x 50 mL), dried (hydrophobic frit) and evaporated to dryness. The product was purified by chromatography on silica using a gradient elution from 0% to 100% methyl tert-butyl ether in cyclohexane to afford the title compound (1.4 g, 4.8 mmol, 72 % yield). LCMS RT= 1.26 min, ES+ve m/z 312 [M+H]+.

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

Reference:
Patent; YALE UNIVERSITY; GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED; CAMBRIDGE ENTERPRISE LIMITED UNIVERSITY OF CAMBRIDGE; CREWS, Craig, M.; BUCKLEY, Dennis; CIULLI, Alessio; JORGENSEN, William; GAREISS, Peter, C.; MOLLE, Inge, Van; GUSTAFSON, Jeffrey; TAE, Hyun-Seop; MICHEL, Julien; HOYER, Dentin, Wade; ROTH, Anke, G.; HARLING, John, David; SMITH, Ian Edward, David; MIAH, Afjal, Hussain; CAMPOS, Sebastian, Andre; LE, Joelle; WO2013/106646; (2013); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

541-16-2, Adding some certain compound to certain chemical reactions, such as: 541-16-2, name is Di-tert-Butyl malonate, 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 541-16-2.

General procedure: alpha,beta-Unsaturated aldehyde (3.0 mmol) and malonate (3.0 mmol) were added into asolution of TiCl4 (6.0 mmol) in CCl4 (2.0 mL) and THF (10 mL) at 0 C, Then, pyridine (0.96 mL, 12.0 mmol) in THF (2 mL) was added dropwisely over 1 h. The resulting mixture was stirred at room temperature overnight. After quenched with water, the mixture was extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography with hexane/ethyl acetate = 20/1 to afford the product.

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 541-16-2.

Reference:
Article; Wei, Xu; Lu, Junzhu; Duan, Wei-Liang; Synthesis; vol. 48; 23; (2016); p. 4155 – 4160;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 31930-34-4, name is Ethyl cis-3-Bromoacrylate, 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 31930-34-4, 31930-34-4

General procedure: Pd(PPh3)4 (0.047g, 0.042 mmol) and CuI (0.016g, mmol) were dissolved in degassed NEt3 (11 mL). (Z)- Ethyl 3-bromopropenoate1 (0.75 g, 4.2mmol) was dissolved in degassed NEt3 (1.8 mL) and slowly added to the reaction mixture. After 5 minutes, propargyl alcohol (0.23 g, 4.1 mmol) in degassed NEt3 (1.8 mL) was added dropwise and the mixture was stirred for 24 h. The contents of the flask were filtered through Celite and washed with hexanes. Saturated NH4Cl solution was added to the filtrate, which was subjected to a conventional extractive workup (CH2Cl2)(3x). The residue (0.250 g, 1.62 mmol) was dissolved in 50 mL of CH2Cl2 (50 mL) and the solution was cooled to 0 C. Excess Co2(CO)8 was added to the flask and the mixture was stirred for 30 minutes. The solution was removed from the ice bath and allowed to come to room temperature while stirring for an additional 2 h. Following solvent removal under reduced pressure, the crude product was dissolved in petroleum ether and filtered through a silica plug. The silica gel was first washed with petroleum ether to flush out excess Co2(CO)8 and then washed with diethyl ether to collect hexacarbonyl [mu-eta4((Z)- ethyl 6-hydroxyhex-2-en-4-ynoate)]dicobalt (1.103 g, 60%). IR (neat): 3465, 2984, 2902, 2051, 2002, 1704; 1H NMR : 7.03 (d, J=11.4, 1H), 5.88 (d,J=11.4, 1H), 4.87 (d, J=6.9, 2H), 4.17 (q, J=7.2, 2H), 4.11 (t, J=6.9, 1H), 1.26 (t, J=7.2, 3H); 13C NMR :198.8, 166.4, 142.8, 117.2, 98.0, 79.8, 64.5, 60.64, 14.0; MS EI m/e: 384 (M+ -2CO), 356 (M+ – 3CO), 328(M+ – 4CO), 272 (M+ – 6CO); HRMS for C14H10Co2O9, calcd (M+-2CO) 383.9090, found 383.9091.To a solution of hexacarbonyl[mu-eta4((Z)- ethyl 6-hydroxyhex-2-en-4-ynoate)]dicobalt (0.363 g,0824 mmol) was stirred in acetic anhydride (1.5 mL) and pyridine (1.5 mL), starting at 0C and warming up to room temperature. After 2 hours, the reaction was placed under reduced pressure to obtain crude product and flash chromatography was performed (10:1 petroleum ether: diethyl ether) to yield (10) as a dark red oil (0.3599 g, 91%). IR (neat) 2960, 2094, 2054, 2019, 1744, 1719; 1H NMR : 7.07 (d, J = 11.4,1H), 5.93 (d, J = 11.4, 1H), 5.478 (s, 2H), 4.18 (q, J = 7.1, 2H), 2.14 (s, 3H), 1.29 (t, J = 7.1, 3H); 13C NMR :198.8, 170.8, 165.1, 141.6, 118.5, 109.6, 93.8, 79.7, 66.2, 60.3, 20.5, 14.2; MS EI m/e: 398 (M+ – 3CO),370 (M+ – 4CO), 342 (M+ – 5CO), 314 (M+ – 6CO); HRMS for C16H12Co2O10, calcd (M+-3CO) 397.9247,found 397.9262.

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 cis-3-Bromoacrylate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Mahmood, Aqsa; Ngenzi, Rebecca; Penner, Page M.; Green, James R.; Synlett; vol. 27; 8; (2016); p. 1245 – 1250;,
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These common heterocyclic compound, 106614-28-2, name is Methyl 2,4-difluorobenzoate, 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. 106614-28-2

To a 8 mL sealed tube was added (1S,4S,5R)-5-[[l-(2-chloro-6-methylphenyl)-4- cyclopropyl-1H-pyrazol-5-yl]methoxy]-2-azabicyclo[2.2.1]heptane 8g (100 mg, 0.28 mmol, 1.00 equiv.), methyl 2,4-difluorobenzoate (72 mg, 0.42 mmol, 1.50 equiv.), CsF (0.134 g, 3.00 equiv.), and l-Ethyl-3-methylimidazolium dimethyl phosphate (1 mL). The resulting mixture was heated at 90 C overnight. After cooling to room temperature, the mixture was diluted with 20 mL of H2O, and extracted with ethyl acetate (100 mL x 2). The combined organic extracts were washed with brine (100 mL x 2), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by silica gel column chromatography eluting with ethyl acetate/petroleum ether (1 :2) to afford methyl 4-[(1S,4S,5R)-5-[[l-(2-chloro-6-methylphenyl)-4- cyclopropyl-1H-pyrazol-5-yl]methoxy]-2-azabicyclo[2.2.1]heptan-2-yl]-2-fluorobenzoate 8h (91 mg, 64%) as a red oil.

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 106614-28-2.

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

Adding some certain compound to certain chemical reactions, such as: 455-68-5, name is Methyl 3-fluorobenzoate, 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 455-68-5. 455-68-5

REFERENCE EXAMPLE 68 Dimethyl 2-m-fluorophenyl-2-oxoethylphosphonate (68) STR87 To a stirred solution of dimethyl methylphosphonate (10.1 g, 81.2 mmol) in 100 ml of anhydrous THF was added dropwise n-butyl lithium (1.58N, 51.4 ml, 81.2 mmol) at -78¡ã C. under argon atmosphere. After 30 minutes, methyl m-fluorobenzoate (5.0 g, 32 mmol) was further added dropwise and the mixture was stirred for 30 minutes. The reaction solution was allowed to warm to 0¡ã C., diluted with 4.9 ml of acetic acid and 10 ml of water, and concentrated. 30 ml of water was added to the residue and the mixture was extracted with ethyl acetate (50 ml*2). The combined ethyl acetate layers were washed with water (20 ml*1) and brine (20 ml*1), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled under reduced pressure to give an oil of dimethyl 2-m-fluorophenyl-2-oxo-ethylphosphonate (6.6 g, 26.8 mmol, yield 83.8percent, b.p. 132¡ã-134¡ã C./0.17 mmHg), which was assigned the structure by the following data: IR(Liquid film method): 3450, 3060, 2940, 2840, 1680, 1580, 1475, 1430, 1400, 1290, 1260, 1190, 1110, 1055, 1030, 870, 825, 790, 760, 710, 665 cm-1. NMR (90 MHz, CDCl3, delta): 3.62(2H, d, J=22.6 Hz), 3.79(6H, d, J=11.4 Hz), 7.15-7.9(4H, m).

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 Methyl 3-fluorobenzoate.

Reference:
Patent; Toray Industries, Inc.; US4775692; (1988); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

110-42-9, 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. 110-42-9 name is Methyl decanoate, 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.

EXAMPLE 7 13.5 g (0.083 mole) of diethylene glycol monobutyl ether was added dropwise to a mixture consisting of 1.6 g (0.042 mole) of sodium borohydride, 10 ml of xylene and 5 g (0.027 mole) of methyl caprate at 95 C. over two hours while agitating the mixture. Subsequently, the mixture was agitated at the same temperature for two hours. After cooling to room temperature, the mixture was neutralized with dilute sulfuric acid. As a result, n-decanol was obtained in 98% yield.

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

Reference:
Patent; Kao Corporation; US5196601; (1993); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics