Month: November 2020

Some common heterocyclic compound, 42726-73-8, name is tert-Butyl methyl malonate, molecular formula is C8H14O4, 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. 42726-73-8

Example 2; Preparation of Compound 2; Compound 1 (7 g), tert-butyl methyl malonate (6 g), 0.5 ml of piperidine and 0.3 ml of acetic acid are heated under reflux for three hours in 100 ml of methanol. After cooling to room temperature, the mixture is filtered and the filtrate is concentrated. The concentrated filtrated is poured into water, and resulted precipitate is filtered off with suction to collect the solid that is air-dried. The crude product is further purified with silica gel chromatography to yield the desired Compound 2.

The chemical industry reduces the impact on the environment during synthesis tert-Butyl methyl malonate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AAT Bioquest, Inc.; US8318953; (2012); B2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

538-23-8, A common compound: 538-23-8, name is Propane-1,2,3-triyl trioctanoate, belongs to esters-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

Two mg of a free astaxanthin (manufactured by Sigma) and 300 mg of tricaprilin as a triglyceride form fatty acid were placed in a brown glass bottle. Three hundred mg of immobilized lipase prepared by the method described in the example of lipase immobilization was added thereto, and 30 muL of water and 12 ml of n-hexane were further added thereto and stirred fully afterwards. Thereafter, while stirring, reaction was carried out at 45C. Three days later, the reaction product was taken out. The immobilized enzyme was eliminated by decantation, and the supernatant hexane was eliminated. The composition ratio of astaxanthin was then analyzed by HPLC. As a result, the composition ratio was 64.1% astaxanthin, 23.9% monoester, and 2.3% diester.

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, Propane-1,2,3-triyl trioctanoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SUNTORY LIMITED; EP1500645; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

14062-25-0, 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 14062-25-0 as follows.

Ethyl-2-(4-bromophenyl)-2-diazoacetate (5j). To a solution of ethyl-4-bromophenylacetate (9j) (400 mg, 1.65 mmol) and 4-acetamidobenzenesulfonylazide (p-ABSA) (593 mg, 2.47 mmol) in dry CH3CN (4 mL) at 0C 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (376 mg, 2.47 mmol) was added. The mixture was stirred at it overnight, poured onto water (30 mL) andextracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (40 mL), dried over Na2SO4 and the solvent evaporated under reduced pressure. The residue was dissolved in C112C12 (30 mL) whereby the side product 4-acetamidobenzenesulfonamide precipitated as a white solid. The suspension was filtered through silica gel and concentrated to afford an orange solid 5j (359 mg, 81 %).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 14062-25-0, and friends who are interested can also refer to it.

Reference:
Patent; ALLOCYTE PHARMACEUTICALS AG; BREITENSTEIN, Werner; HUERZELER, Marianne; KELLY, Terence; MANCUSO, Riccardo; SCHNEIDER, Gisbert; WEITZ-SCHMIDT, Gabriele; WO2015/189265; (2015); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 42726-73-8, name is tert-Butyl methyl malonate, 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 42726-73-8, 42726-73-8

tert-Butyl methyl malonate (3.9 mL, 23 mmol), potassium carbonate (7.9 g, 57.5 mmol) and dibromoethane (2.57 mL, 29.9 mmol) were combined in DMF (75 mL) and the resulting reaction mixture was stirred at room temperature overnight. The mixture was poured onto water (500 mL) and extracted with ether (3 X). The combined ethereal layers were washed with water, then washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography (0-5percent EtOAc/ hexane) provided l-(tert-butyl) 1-methyl cyclopropane-l,l-dicarboxylate (2.35 g, 51percent yield). Combined with another batch afforded the desired product (4.28 g). 1H NMR (300 MHz, Chloroform-d) delta 3.75 (s, 3H), 1.47 (s, 9H), 1.38 (s, 4H).

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 methyl malonate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; UNIVERSITY OF HAWAII; TURKSON, James; YUE, Peibin; TIUS, Marcus; BROTHERTON-PLEISS, Christine; LOPEZ TAPIA, Francisco, Javier; (420 pag.)WO2018/136935; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

4518-10-9,Some common heterocyclic compound, 4518-10-9, name is Methyl 3-aminobenzoate, molecular formula is C8H9NO2, 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.

EXAMPLE 13-[2-(2,4,6-Trihydroxy-phenyl)-acetylamino]-benzoic acid (18)SCLiOH H2O/TIH F EPO Step 1: (The following reaction is done in an anhydrous N2 atmosphere.) Dissolve EDC hydrochloride (122mg, 0.64mmol) and triethylamine (89muL, 0.64mmol) in anhydrous dichloromethane (3.2mL) and stir for 5min at rt. Add 2-(2,4,6-Trimethoxyphenyl)- acetic acid (14) (lOlmg, 0.45mmol) and DMAP (8mg, O.Ommol) and stir for lOmin. Add ethyl ester (15) (70mg, 0.42mmol) and stir the reaction solution overnight at rt. Hydrolize the reaction solution with saturated aqu. NH4Cl followed by water, separate layers, extract aqu. layer with dichloromethane (3 times) and wash the combined organic layers with water and brine and dry with Na2SO4. Remove solvent under reduced pressure. Purify crude product by preparative radial chromatography (silica gel 60PF, EtOAc/CyH 1+1) to obtain 3-[2- (2,4,6-Trimethoxy-phenyl)-acetylamino]-benzoic acid methyl ester (16) as a white solid (145mg, 95%). [K. C. Nicolaou; P. S. Baran; Y.-L. Zhong; K. Sugita; J Am. Chem. Soc; 2002; 124; 10; 2212-2220]. 1H NMR (400MHz, CDCl3): 3.68 (s, 2 H); 3.83 (s, 3 H); 3.84 (s, 6 H); 3.87 (s, 3 H); 6.18 (s, 2 H); 7.33 (t, 1 H, J= 8.0Hz); 7.56 (br.s, 1 H); 7.69 (br.dd, 1 H, J= 7.8Hz); 7.78 (t, 1 H, J= 1.8Hz); 7.90 (dd, I H1 J/ = 8.1Hz, J2 = 1.3Hz).

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

Reference:
Patent; REVOTAR BIOPHARMACEUTICALS AG; WO2007/39112; (2007); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

A common heterocyclic compound, 764667-64-3, name is 5-(1-Hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione, molecular formula is C14H11F3O5, 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. 764667-64-3.

2,4, 5-TRIFLUOROPHENYLACETIC acid (2-1) (150 g, 0.789 mol), Meldrum’s acid (125 g, 0. 868 mol), and 4- (DIMETHYLAMINO) pyridine (DMAP) (7.7 g, 0063 mol) were charged into a 5 L three-neck flask. N, N-DIMETHYLACETAMIDE (DMAC) (525 ML) was added in one portion at room temperature to dissolve the solids. N, N-diisopropylethylamine (282 ML, 1.62 mol) was added in one portion at room temperature while maintaining the temperature below 40 C. Pivaloyl chloride (107 ML, 0.868 mol) was added dropwise over 1 to 2 h while maintaining the temperature between 0 and 5 C. The reaction mixture was aged at 5 C for 1 h. Triazole hydrochloride 1-4 (180 g, 0.789 mol) was added in one portion at 40-50 C. The reaction solution was aged at 70 C for several h. 5% Aqueous sodium hydrogencarbonate solution (625 ML) was then added dropwise at 20-45 C. The batch was seeded and aged at 20-30 C for 1-2 h. Then an additional 525 mL of 5% aqueous sodium hydrogencarbonate solution was added dropwise over 2-3 h. After aging several h at room temperature, the slurry was cooled to 0-5 C and aged 1 h before filtering the solid. The wet cake was displacement-washed with 20% aqueous DMAC (300 mL), followed by an additional two batches of 20% aqueous DMAC (400 mL), and finally water (400 mL). The cake was suction-dried at room temperature. The isolated yield of final product 2-3 was 89%.

The synthetic route of 5-(1-Hydroxy-2-(2,4,5-trifluorophenyl)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; WO2005/20920; (2005); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

37746-78-4, A common compound: 37746-78-4, name is (E)-Ethyl 4-bromobut-2-enoate, belongs to esters-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

General procedure: To a vigorously stirring solution of alpha-imino ester 1 (0.5 mmol,1 equiv) and E-ethyl-4-bromocrotonate or methyl-4-bromocrotonate (2, 1.5 mmol, 3 equiv) in EtOH (2 mL) was added indium powder (1 mmol, 2 equiv). The mixture was allowed to stir vigorously for 6 h at 30 C. After this period, the reaction mixturewas quenched with 2 mL of water and transferred to a separating funnel and extracted using ethyl acetate (315 mL). The combined organic layers were dried over anhydrous Na2SO4. Then the solvent was evaporated under vacuum. Purification of the resulting crude reaction mixture by column chromatography on silica gel (EtOAc/Hexane as eluent) gave the product 3 (see Tables 1 and 2 and Scheme 2 for individual entries).

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, (E)-Ethyl 4-bromobut-2-enoate, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Aslam, Nayyar Ahmad; Babu, Srinivasarao Arulananda; Sudha, Arya Jayadev; Yasuda, Makoto; Baba, Akio; Tetrahedron; vol. 69; 32; (2013); p. 6598 – 6611;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

27007-53-0, A common compound: 27007-53-0, name is Methyl 2-bromo-5-chlorobenzoate, belongs to esters-buliding-blocks compound, it can change the direction of chemical reaction, and react with certain compounds to generate new functional products. A new synthetic method of this compound is introduced below.

A solution of 2-bromo-5-chloro-benzoic acid methyl ester Compound 4-2 (5.08 g, 20.4 mmol), the boronate Compound 4-1 (6.00 g, 19.4 mmol), PdCl2dppf-CH2Cl2 (1.06 g, 1.30 mmol) and K2CO3 (8.9 g, 58.21 mmol) in DMF and EtOH (4:1, 90 mL) was prepared in a thick walled tube. The mixture was stirred under argon at rt for 5-10 min and the tube was closed and heated at 90 C. for 5 hrs (4-16 hrs for other examples). The mixture was cooled to rt then filtered thru a pad of Celite, washing with EtOAc. The solvent was evaporated and purified by flash chromatography (gradient elution with 5-50% EtOAc in heptane with 0.1% TEA). The desired product Compound 4-3 was isolated as yellow liquid (4.05 g, 60%). 1H NMR (300 MHz, CDCl3) delta 7.82 (d, J=2.2 Hz, 1H), 7.43 (d of d, J=8.2 and 2.2 Hz, 1H), 7.14 (d, J=8.2 Hz, 1H), 5.51 (br s, 1H), 4.02 (br s, 2H), 3.85 (s, 3H), 3.63 (t, J=5.6 Hz, 2H), 2.30 (br s, 2H), 1.50 (s, 9H); MS (ES+) m/z 374.0 (M+Na).

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-bromo-5-chlorobenzoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Ghosh, Shyamali; Kinney, William A.; Lawson, Edward C.; Luci, Diane K.; Maryanoff, Bruce E.; Sommen, Francois Maria; Pan, Yongchun; US2008/39454; (2008); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

868-72-4,Some common heterocyclic compound, 868-72-4, name is Dimethyl 2,5-dibromohexanedioate, molecular formula is C8H12Br2O4, 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 stirring solution of dimethyl 2,5-dibromohexanedioate (SM) (50 g, 0.15 mol) in toluene:water (150 mL, 2: 1) were added benzyl amine (16 mL, 0.15 mol) and K2CO3 (24 g, 0.18 mol) at room temperature. The reaction mixture was heated to reflux at 110 C and stirred for 4 h. After consumption of the starting material (by TLC), reaction mixture was cooled to room temperature and extracted with diethyl ether (2 x 50 mL). Separated organic layer was dried over anhydrous Na2S04 and concentrated under reduced pressure to obtain compound 1- mixture (39 g, 93%) as liquid. This material was purified by silica gel column chromatography eluting with 20% EtOAc/n-hexane to afford compound 1-Fl (10 g), compound 1-F2 (13 g) and compound 1-Fl and F2 as a mixture (16 g) as liquid. H NMR (500MHz, CDC13): delta 7.32-7.17 (m, 5H), 3.89 (s, 2H), 3.55 (s, 6H), 3.45-3.38 (m, 2H), 2.08- 1.99 (m, 4H). LCMS (m/z): 278.2 [M++l].

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route Dimethyl 2,5-dibromohexanedioate, its application will become more common.

Reference:
Patent; APTINYX INC.; KHAN, Amin, M.; (197 pag.)WO2018/26792; (2018); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

These common heterocyclic compound, 426-65-3, name is Ethyl Pentafluoropropionate, 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. 426-65-3

General procedure: Sodium hydride (4.0 g, 100 mmol, 60% dispersion in mineral oil) was placed in a 500mL round-bottom flack and 50 mL of dry hexane was added. The suspension was stirred for a short time with a magnetic stirring bar and kept until the hexane layer became clear (20-30 min). Hexane was cautiously removed with a glass pipette until a wet paste of NaH remained. This procedure was repeated twice. After that, THF (150mL) was added with vigorous stirring. Anhydrous EtOH (0.5 mL) was added in oneportion at 0 C, followed by the dropwise addition of a solution of 2-acetylthiophene (6.3g, 50 mmol, 5.42 mL) and methyl or ethyl ester of the respective perfluorinatedcarboxylic acid (50.5 mmol) in 30 mL of THF. The white suspension rapidly turns pink and then reddish-brown. Caution Hydrogen evolved during the addition and notable effervescence was observed. The rate of addition was maintained to control the evolution of hydrogen; usually the addition takes 60-80 min. When gas evolution ceased, the cooling bath was removed and the reaction mixture was stirred for 5 h. After that, the dark brown solution with a small amount of precipitate was re-cooled to 0 C,10 mL of anhydrous EtOH was added slowly to decompose traces of NaH, and the resulting solution was stirred for 30 min. The solvent was removed by evaporation under reduced pressure (100 Torr, bath temperature 40 C), then EtOAc (40 mL) andsubsequently a mixture of conc. HCl (20 mL) and crushed ice (80 mL) were added tothe residue. The resulting turbid liquid was shaken by hand until two clear layers formed. The organic phase was separated and the aqueous phase was then extracted with EtOAc (3 ¡Á 50 mL). The combined organic fractions were washed with brine (50mL), dried over MgSO4 and evaporated to dryness. The resulting brown oil was distilled in vacuo (2-3 Torr). The main fraction is pure enough. Additional portions of pure diketone can be separated from low-boiling fractions by precipitation as a copper salt. Decomposition should be performed with HCl (procedure A).

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 426-65-3.

Reference:
Article; Taydakov, Ilya V.; Kreshchenova, Yuliya M.; Dolotova, Ekaterina P.; Beilstein Journal of Organic Chemistry; vol. 14; (2018); p. 3106 – 3111;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics