Month: February 2021

Related Products of 2435-36-1,Some common heterocyclic compound, 2435-36-1, name is Dimethyl cyclopentane-1,3-dicarboxylate, molecular formula is C9H14O4, 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 solution of HMPA (13.08 mL, 75 mmol) and LDA (13.43 mL, 26.9 mmol) in THF (30 mL) was added a solution of dimethyl cyclopentane-1, 3-dicarboxylate (2 g, 10.74 mmol) in 10 mL THF dropwise over 30 minutes at -78 under N2protection and stirred at one point for another 30 minutes. The solution was warmed to 0 and stirred at one point for 1 hour. The solution was cooled to -78 and added a solution of 1-bromo-2-chloroethane (1.848 g, 12.89 mmol) in 10 mL THF dropwise. The solution was stirred at -78 for 1 hour and warmed to RT. Afrer stirred for 16 hours, the solution was added 1N HCl and extracted with EtOAc. The combined organic layer was dried over Na2SO4, concentrated in vacuo to give the title compound.1H NMR (CDCl3400 MHz) : 3.67 (s, 6H) , 2.01 (d, J6.7 Hz, 4H) , 1.89 (s, 2H) , 1.66 (d, J6.7 Hz, 3H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Dimethyl cyclopentane-1,3-dicarboxylate, its application will become more common.

Reference:
Patent; MERCK SHARP & DOHME CORP.; LIU, Jian; KOZLOWSKI, Joseph A.; ALHASSAN, Abdul-Basit; BOGA, Sobhana Babu; GAO, Xiaolei; GUIADEEN, Deodialsingh; WANG, Jyhshing; YU, Wensheng; CAI, Jiaqiang; LIU, Shilan; WANG, Dahai; WU, Hao; YANG, Chundao; (260 pag.)WO2016/106623; (2016); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 252881-74-6, 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. 252881-74-6, name is tert-Butyl 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Acetylenedicarboxylic acid (0.35 g, 3.09 mmol, 1.0 eq.) was dissolved in NMP (10 mL) and cooled to 0 C, to which compound 34 (2.06 g, 7.43 mmol, 2.4 eq.) was added, followed by DMTMM (2.39 g, 8.65 mmol, 2.8 eq.) in portions. The reaction was stirred at 0 C for 6 h and then diluted with ethyl acetate and washed with water and brine. The organic solution was concentrated and triturated with a mixture solvent of ethyl acetate and petroleum ether. The solid was filtered off and the filtrate was concentrated and purified by column chromatography (80-90% EA/PE) to give a light yellow oil (2.26 g, >100% yield), which was used without further purification. MS ESI m/z [M+H]+ 633.30.

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 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; HANGZHOU DAC BIOTECH CO, LTD; ZHAO, Robert Yongxin; YANG, Qingliang; HUANG, Yuanyuan; GAI, Shun; YE, Hangbo; YANG, Chengyu; GUO, Huihui; ZHOU, Xiaomai; XIE, Hongsheng; TONG, Qianqian; CAO, Minjun; ZHAO, Linyao; JIA, Junxiang; LI, Wenjun; ZUO, Xiaotao; LIN, Chen; XU, Yifang; GUO, Zixiang; (274 pag.)WO2017/46658; (2017); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Some common heterocyclic compound, 27829-72-7, name is Ethyl E-hex-2-enoate, molecular formula is C8H14O2, 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 C8H14O2

(1) Ethyl 2,3-methanohexanoate 15.6 g. of sodium hydride (content 65.1percent, 0.423 mol) were suspended in 800 ml. of dimethyl sulphoxide, and there were added, with stirring, 154 g. (0.7 mol) of trimethyloxosulphonium iodide in small portions at 20¡ã to 30¡ãC. over a period of 20 minutes. An exothermic reaction took place with the evolution of hydrogen. After stirring for 10 minutes, there was added, dropwise, a solution of 60 g. (0.423 mol) of ethyl hex-trans-2-enoate in 70 ml. of dimethyl sulphoxide at 20¡ã to 30¡ãC. The reaction mixture was stirred at 40¡ãC. for 3 hours and then poured into 2 litres of ice-water and extracted with diethyl ether. The aqueous layer was treated with 60 ml. of concentrated hydrochloric acid and extracted with diethyl ether. The combined ethereal layer was washed with water, dried with magnesium sulphate and concentrated under reduced pressure. Distillation of the crude product gave 23.2 g. of ethyl 2,3 -methanohexanoate having the following physical characteristics:- b.p. 57¡ã to 60¡ãC./6 mm.Hg; NMR (CDCl3 and CCl4 solution); delta: 4.05 (2H, q), 0.95 (3H, t) and 0.70-0.48 (2H, dd); IR (liquid film); nu: 2950, 1720, 1450, 1405, 1370, 1330, 1265, 1200, 1180, 1100, 1040, 860 cm-1.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 27829-72-7, its application will become more common.

Reference:
Patent; Ono Pharmaceutical Co., Ltd.; US3978229; (1976); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 35598-05-1, These common heterocyclic compound, 35598-05-1, name is Methyl 4-methoxy-2-methylbenzoate, 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.

[00121] Step 1 : Methyl 2-(bromomethyl)-4-methoxybenzoate[00122] To a solution of methyl 4-methoxy-2-methylbenzoate (1 g, 5.6 mmol) inCC14 (25 mL) was added dropwise N-bromosuccinimide (1.1 g, 6.2 mmol) previously dissolved in CC14 (5 mL) and a catalytic amount of benzoyl peroxide. The mixture was refluxed for 2 hours, cooled to room temperature and poured onto iced water. The aqueous mixture was extracted with DCM (3x), and the combined organics were dried over MgS04, filtered, and concentrated in vacuo to provide 2.1 g of the titled product as light yellow solid (~ 100% yield): [M+H+] m/z 260.

Statistics shows that Methyl 4-methoxy-2-methylbenzoate is playing an increasingly important role. we look forward to future research findings about 35598-05-1.

Reference:
Patent; SELEXAGEN THERAPEUTICS, INC.; VERNIER, Jean-Michel; MAY, John; O’CONNOR, Patrick; RIPKA, William; PINKERTON, Anthony; BOUNAUD, Pierre-Yves; HOPKINS, Stephanie; WO2011/85128; (2011); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 6279-86-3, name is Triethyl methanetricarboxylate, 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 6279-86-3, SDS of cas: 6279-86-3

Example IEthyl 2,4-dihvdroxy-7,7-dimethyl-5-oxo-5,6,7,8-tetrahvdroquinoline-3-carboxylate10 g 3-Amino-5,5-dimethyl-2-cyclohexen-1 -one and 25 g 2-Ethoxycarbonyl-malonic acid diethyl ester are combined and heated for 10 minutes at 210C (bath temperature).Thereafter the mixture is cooled to room temperature and triturated with diethylether. The crystalline precipitate is collected by filtration and dried in vacuo.Yield: 9,9 g (49 % of theory)Mass spectrometry (ESI+): m/z = 280 [M+H]+ Rf-value: 0,45 (silica gel, dichloromethane/methanol 9:1 )

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; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; WAGNER, Holger; BERTA, Daniela; FUCHS, Klaus; GIOVANNINI, Riccardo; HAMPRECHT, Dieter, Wolfgang; KONETZKI, Ingo; STREICHER, Ruediger; TRIESELMANN, Thomas; WO2011/101424; (2011); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 51329-15-8, name is Methyl 3,5-dibromobenzoate, 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 51329-15-8, category: esters-buliding-blocks

a) 3-Bromo-5-hydroxy-benzoic acid methyl ester. A 5 mL tube was charged with 3,5-dibromo-benzoic acid methyl ester (586 mg, 2.0 mmol), bis(pinacolato)diboron (254 mg, 1.0 mmol), potassium acetate (294 mg, 3.0 mmol) and PdCl2(dppf) complex (50 mg). DMSO (3 mL) was added, and the solution was degassed with nitrogen, then the tube was sealed. After heating the tube for 16 h at 80 C., the mixture was diluted with ethyl acetate (10 mL) and extracted with brine (10 mL, three times), and saturated aqueous sodium bicarbonate (5 mL), and the organic layer was dried and concentrated to give 3-bromo-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester. To a solution of this material in acetone (4 mL) was added an aqueous solution of Oxones (2 KHSO5.KHSO4.K2SO4) (1.23 g in 5 mL water), and the reaction mixture was stirred vigorously for 8 min at room temperature. The reaction mixture was quenched with aqueous sodium hydrogensulfite. The brown solution was extracted with ethyl acetate, and the organic layer was extracted with brine and water, dried and concentrated. The residue was passed through a short silica gel column using a gradient of methylene chloride to 2% methanol in methylene chloride as an eluent to give 104 mg of 3-bromo-5-hydroxy-benzoic acid methyl ester.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Methyl 3,5-dibromobenzoate, and friends who are interested can also refer to it.

Reference:
Patent; Locus Pharmaceuticals, Inc.; US2008/280891; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 122-72-5,Some common heterocyclic compound, 122-72-5, name is 3-Phenylpropyl Acetate, molecular formula is C11H14O2, 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.

General procedure: In a typical example, a substituted benzene (1.0mmol), as shown in Table 6, was treated with H2 (30atm) with stirring at 30 or 50C in the presence of Ru-1 (Ru=0.003mmol, S/C=333, in 1mL of H2O) in an autoclave with an inner glass tube. The product was extracted with EtOAc (3mL¡Á5) and the combined extracts were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified using a short silica gel column. The hydrogenation of anisole on a large scale [toluene=24mmol (S/C=1400)] is described in the Supplementary data.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3-Phenylpropyl Acetate, its application will become more common.

Reference:
Article; Gao, Lei; Kojima, Keisuke; Nagashima, Hideo; Tetrahedron; vol. 71; 37; (2015); p. 6414 – 6423;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 3618-04-0, name is trans-Ethyl 4-hydroxycyclohexanecarboxylate, 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 3618-04-0, Quality Control of trans-Ethyl 4-hydroxycyclohexanecarboxylate

To a solution of ethyl 4-hydroxycyclohexanecarboxylate (5.00 g, 29.0 mmol) in dichloromethane (30 mL) was added 3,4-dihydro-2H-pyran (2.52 g, 29.0 mmol) and Amberlyst 15 (0.5 g). The reaction mixture was stirred at room temperature for 72 h, then another prtion 3,4-dihydro-2H-pyran (1.89 g, 21.8 mmol) and Amberlyst 15 (0.5 g) was added, then after 5 h the reaction mixture was washed with sat. aq. sodium hydrogencarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated to afford the title compound as a yellow oil (9 g), which was used directly in the next step.

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

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; DEHMLOW, Henrietta; MARTIN, Rainer E.; MATTEI, Patrizio; OBST SANDER, Ulrike; RICHTER, Hans; WO2013/60653; (2013); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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 193290-19-6 as follows. name: Methyl 2-(4-bromo-2-fluorophenyl)acetate

To a solution of methyl 2-(4-bromo-2-fluorophenyl) acetate (1 g, 4.05 mmol) in toluene/THF H20 (15 mL, v/v/v=2/2/l ) were added 2-methylpyridin-3-ylboronic acid (870 mg, 3.97 mmol), AcO (790 mg, 8.05 mmol) and PdCl2(dppf) (222 mg, 0.31 mmol) under nitrogen. The reaction mixture was stirred at 90C for 15 h. The reaction mixture was filtered, the filtrate was washed with water, extracted with EtOAc (2 x 10 mL). The combined layers were washed with brine, dried over Na2S04 and concentrated. The residue was purified by column chromatography on silica gel eluted with 0- 10% EtOAc in petroleum ether to afford the desired product (0.9 , 86%). LCMS m/z 260 (M+l )+.

According to the analysis of related databases, 193290-19-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; AFRAXIS, INC.; CAMPBELL, David; DURON, Sergio, G.; WO2013/43232; (2013); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 35180-01-9, 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. 35180-01-9 name is Chloromethyl isopropyl carbonate, 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.

Diesterification reaction: Under a nitrogen atmosphere, 100 g Tenofovir (PMPA) And 300ml N-methylpyrrolidone (NMP), the control temperature at 25 ~ 30 , shaking 30min, To dissolve, and then add 106g triethylamine (TEA), 20 ~ 30 shaking 30min until uniform; The above mixture was warmed to 60 ~ 65 , and stirred, In 15 ~ 20min rapid dropping 266g chloromethyl isopropyl carbonate (CMIC) Then warmed to 75 ~ 80 , shaking reaction 60 ~ 70min, When TLC real-time monitoring of the basic reaction of the reaction material completely (3% or less), and monoester content of 15% or less, When the area of the main peak of the product is more than 80%, the double esterification reaction is complete; Then the reaction system first use water bath cooling 5min, After using ice-water bath in 10-15 min the reaction system rapidly reduced to 10-15 ;Extraction and Separation: To the reaction system in step (1) was added 600 ml of ethyl acetate (EA) Heated at 10 ~ 15 , stirred for 15min and filtered, each time with 200ml ethyl acetate (EA) washed the filter cake three times, And the filtrate and the resulting filtrate was combined, to which was added 400ml 10 ~ 15 distilled cold water, Full shock, extraction and separation, the separated aqueous phase was extracted with ethyl acetate twice, The resulting organic phase was combined with the EA layer, washed twice with 1000 ml of distilled water, 300g of sodium chloride was added into the obtained water washing solution twice, dissolved with stirring and cooled down to 10 to 15 C, And then extracted with 500ml of ethyl acetate once, the organic phase was extracted and combined, Washed with 900 to 1000 ml of saturated saline (300 g of sodium chloride dissolved in 850 ml of distilled water) Finally, the organic phase was added 400g anhydrous sodium sulfate 60min after drying filtration;Salt-forming reaction: to step (2) dried and filtered about 2000ml filtrate was added to the reaction vessel, Then 32g fumaric acid (FMA) was added and the temperature was raised to 40 C in a nitrogen atmosphere and the reaction was stirred until the solution became clear. (4) Preparation of tenofovir disoproxil fumarate crude product: Step (3) The reaction solution was concentrated under reduced pressure at 40 C, most of the solvent was distilled off until a large amount of crystals were precipitated, Then the concentrate was naturally cooled to room temperature, and then placed in a -5 C freezer was allowed to cool more than 2h, filtered, The resulting filter cake was washed with a small amount of ethyl acetate 2 to 3 times, pumping dry weighed about 130g, 40 under blast drying 2h, weighed to give 85g Tenofovir disoproxil fumarate crude product, The HPLC detector purity of 98% or more;Recrystallization: Under a nitrogen atmosphere, the reaction vessel was charged with step (4) 85 g crude Tenofovir disoproxil fumarate and 500 ml isopropanol (IPA) The nitrogen atmosphere was warmed to 55 C and stirred for 15 min to clarify the solution. If not, the filtrate should be filtered and the filtrate rapidly crystallized. After the resulting solution was left to cool to room temperature, Placed in a freezer at 4 frozen 2h above, so recrystallized, filtered, rinsed with cold isopropyl alcohol cake, Drained, to obtain white wet crystal 108g, at 40 blast drying 2h or 40 under reduced pressure drying 4h, 72 g of tenofovir disoproxil fumarate finished product was obtained. Tenofovir disoproxil fumarate obtained by the above method was tested by HPLC, Its purity is higher than 99.5%, monoester is less than 0.5%, the sum of other impurities is not more than 0.1%, with tenofovir, The total molar yield is about 35-40%.

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

Reference:
Patent; Jiangsu Han Sitong Pharmaceutical Co., Ltd.; Wang Duoping; Wei Genghu; Shi Jiagui; Yang Yu; (7 pag.)CN107400145; (2017); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics