Esters-buliding-blocks

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,
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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,
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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;,
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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,
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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

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. 41841-16-1, name is Methyl 2-(4-bromophenyl)acetate, A new synthetic method of this compound is introduced below., SDS of cas: 41841-16-1

To a 250 mL two-neck flask were added methyl 2-(4-bromophenyl)acetate (3.0 g, 13 mmol) and THF (50 mL), the mixture was cooled to 0 C and lithium bis(trimethylsilyl)amide in THF (32 mL, 32 mmol, 1 mol/L) was added dropwise. The resulting mixture was stirred for 10 mm and 1,4-dibromopropane (1.7OmL, l7mmol) was added. The mixture was stirred at rt for 24 hours, and saturated aqueous ammonium chloride solution was added, the resulting mixture was extracted with EA (100 mL). The organic layer was washed with saturated brine (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v) = 50/1) to give the title compound as colorless oil (2.0 g, 57%).

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; SUNSHINE LAKE PHARMA CO., LTD.; REN, Qingyun; LIU, Xinchang; HUANG, Jianzhou; ZHANG, Yingjun; GOLDMANN, Siegfried; (342 pag.)WO2019/1396; (2019); 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 773873-95-3 as follows. COA of Formula: C9H6F2O4

Step b: (2,2-Difluoro-benzo[l,3]dioxol-5-yl)-methanol; Crude 2,2-difluoro-benzo[l,3]dioxole-5-carboxylic acid methyl ester (11.5 g) dissolved in 20 mL of anhydrous tetrahydrofuran (THF) was slowly added to a suspension of lithium aluminium hydride (4.10 g, 106 mmol) in anhydrous THF (100 mL) at 0 0C. The mixture was then warmed to room temperature. After being stirred at room temperature for 1 hour, the reaction mixture was cooled to 0 0C and treated with water (4.1 mL), followed by sodium hydroxide (10% aqueous solution, 4.1 mL). The resulting slurry was filtered and washed with THF. The combined filtrate was evaporated to dryness and the residue was purified by silica gel column chromatography to give (2,2-difluoro-benzo[l,3]dioxol-5-yl)- methanol (7.2 g, 76 % over two steps) as a colourless oil.

According to the analysis of related databases, 773873-95-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; WO2008/141119; (2008); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 25542-62-5, 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. 25542-62-5 name is Ethyl 6-bromohexanoate, 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.

Reactions were carried out in a Biotage Initiator 60 Microwave Reactor, employing the 20mL process-scale reactor vials. Thirteen (13) identical reactions at the 10 mmol scale were setup in parallel and processed in serial, as follows: All three (3) reagents and reaction solvent were added to the MW vial in the following sequence; (1) ethyl-bromo-hexanoate (1.77 mL), (2) salicylaldehyde (1.05 mL), (3) cesium carbonate (CS2CO3) (3.91 g) and (4) reaction solvent DMA (17.18 mL). Care was taken to dispense the N-N-dimethylacetamide (DMA) solvent in such a manner so as to wash down the vial walls of reactant or solid base. To each vial was added a magnetic stir bar and fitted with a crimp seal cap and adapter collar. The reactions were than process in the MW Reactor for 10 minutes (at temperature) at 140 C with mixing. Following standard ramp up, fixed hold time at temperature and cool down, samples were kept sealed at ambient temperature until the entire lot was processed. The reaction mixtures were combined and transferred to a 2L separatory funnel. Vial contents were washed with ethyl acetate (EtOAc), and a total EtOAc layer of about 800 mL was added. To this was added 800 mL of 1.0 N NaOH solution, and the two layers were vigorously shaken and mixed and then separated. The NaOH aqueous layer was back-extracted 3 x 250 mL with EtOAc, and all the organic layers were combined (about 750 mL) and washed with 800 mL of 1.0 M citric acid solution. The citric acid layer was again back extracted with EtOAc (3 x 250 mL), and the organic layers were again combined (about 1.5 L) and washed (3 x 500 mL) with brine (saturated NaCl), dried over sodium sulfate (Na2SO t) and concentrated to dryness in vacuo. Silica gel TLC (3: 1 Hexanes-EtOAc) Rf = 0.34 (product), Rf = 0.45, 0.25 (trace impurities). Theoretical yield = 13 x 2.64 g or 34.32 g (130 mmol). Isolation and Observed yield = 33.30 g, (33.30 g/34.32 g x 100) = 97%. NMR (, 13C, COSY) and LCMS (ESI+/-) conform to structure.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, Ethyl 6-bromohexanoate, and friends who are interested can also refer to it.

Reference:
Patent; SALK INSTITUTE FOR BIOLOGICAL STUDIES; MITOKYNE, INC.; EVANS, Ronald; BAIGA, Thomas, J.; BOCK, Mark, G.; DOWNES, Michael; EMBLER, Emi, Kanakubo; FAN, Weiwei; KEANA, John, F.W.; KLUGE, Arthur, F.; NOEL, Joseph, P.; PATANE, Mike, A.; WO2014/165827; (2014); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 36692-49-6, 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 36692-49-6 as follows.

Example 96; (2Z,5Z)-2-[(2,6-dichlorophenyl)imino]-5-{[2-(1-methylethyl)-1H-benzimidazol-6-yl ]methylidene}-1,3-thiazolidin-4-one; (a) methyl 2- (1-methylethyl)-lHbenzimidazole-6-carboxylate; A solution of isobutyraldehyde (0.22 mL, 2.41 mmol) and 40 % aq. sodium hydrogen sulfite (2.6 mL) was stirred at room temperature for 1 h. To this mixture is added a solution of methyl 3,4-diaminobenzoate (0.400 g, 2.41 mmol) in ethanol (2 mL). The resulting solution is heated to reflux overnight. The mixture was diluted in water and the resulting precipitate was collected by filtration to obtain 0.524 g of the desired product in >99 % yield. The crude was used without further purification. [MS (ES+) m/e 219 M+H] +. 1H NMR (400 MHz, CHLOROFORM-d) 8 ppm 8.30 (d, =7=1. 0 Hz, 1 H) 7.93 (dd, J=8. 6,1. 5 Hz, 1 H) 7.54 (d, 8. 6 Hz, 1 H) 3.90 (s, 3 H) 3.30-3. 41 (m, 1 H) 1. 48 (d, 7. 1 Hz, 6 H).

According to the analysis of related databases, 36692-49-6, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2005/82901; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Synthetic Route of 3618-04-0, These common heterocyclic compound, 3618-04-0, name is trans-Ethyl 4-hydroxycyclohexanecarboxylate, 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.

PREPARATION 1: 1 – Allyl-4-(tert-butyl-dimethyl-silanyloxy)-cyclohexanecarbaldehyde; Step a: 4-(/ert-Butyl-dimethyl-silanyloxy)-cyclohexanecarboxylic acid ethyl ester:; [00160] To a 50 mL flask was added 4-hydroxy-cyclohexanecarboxylic acid ethyl ester (5.0 g; 29.0 mmol), imidazole (2.37 g; 34.8 mmol), DMF (30 mL) and ter/-buryldimethylsilyl chloride (4.81 g; 32.0 mmol). The solution was stirred for 78h at 20 0C. The reaction was diluted with EtOAc (100 mL), washed with water 2 x 100 mL), brine (100 mL), dried (MgSO4) filtered and concentrated in vacuo. The crude oil was purified by flash chromatography (silica gel, hexanes/EtOAc 1:0 to 1:1) to give pure product (7.79 g, 94% yield) as a 2:1 mixture of diastereomers.1H-NMR (400 MHz, CDCl3) (J = Hz) delta mixture 4.12 (m; 2H), 3.90 (m; 0.65H), 3.58 (m; 0.35H), 2.23 (m; IH), 1.98 (m; 3H), 1.82 (m; 3H), 1.49 (m; 2H), 1.21 (m; 3H), 0.88 (s; 9H), 0.05 (s; 3H), 0.03 (s; 3H). 13C-NMR (400 MHz, CDCl3) delta mixture 175.7, 175.6, 70.5, 66.6, 60.1, 60.0, 42.2, 42.1, 34.8, 32.8, 27.2, 25.8, 25.6, 23.4, 18.2, 18.0, 14.2, -4.7, -4.9. MS (ES+) m/z 287.22 [MH+].

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

Reference:
Patent; BIOGEN IDEC MA INC; WO2007/76086; (2007); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics