Month: June 2021

Electric Literature of 106-65-0, A common heterocyclic compound, 106-65-0, name is Dimethyl succinate, molecular formula is C6H10O4, 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.

EXAMPLE 11 Methyl alpha-formylsuccinate In a modification of the procedure of Fissekis and Sweet, Biochemistry 1970, 9, 3136-42, sodium methoxide (40.5 g, 0.75 mol) was suspended in dry ether (500 mL) and stirred under nitrogen at 0 C. A mixture of dimethylsuccinate (65.4 mL, 0.50 mol) and methylformate (123 mL, 2.00 mol) was added dropwise over 30 minutes. The reaction mixture was stirred at 0 C. for 2 hours and then at room temperature overnight. Subsequently, the reaction mixture was evaporated to a viscous brown residue which was washed once with petroleum ether and then dissolved in 3 M hydrochloric acid (160 mL). This solution was made weakly acidic with concentrated hydrochloric acid and then extracted with dichloromethane (4*250 mL). The organic phase was dried (MgSO4), filtered and evaporated under reduced pressure. The resulting residue was distilled in a kugelrohr apparatus at 60 C. and 0.6 mBar yielding 52.3 g of a mixture of the title compound and dimethyl succinate in the molar ratio 80:20 (determined by NMR) as a colorless oil. This mixture can be used directly in the following preparation. The product can be isolated free of dimethyl succinate by exchanging the extraction with dichloromethane with a continuous extraction with diethyl ether. However, in our hands this reduced the yield to 34%. Fissekis and Sweet,ibid, had reported a 62% yield. 1H-NMR (DMSO-d6/TMS): delta=3.20 (s, 2H, CH2); 3.59 (s, 3H, OMe); 3.61 (s, 3H, OMe); 7.73 (s, 1H, CHOH); 10.86 (br s, 1H, CHOH). 13C-NMR (DMSO-d6/TMS): delta=28.9 (CH2); 51.0 (OMe); 51.6 (OMe); 102.1 (C=CHOH); 156.6 (CHOH); 168.3 (COO); 171.7 (COO).

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; Nielsen, Peter E.; US6300318; (2001); B1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 2177-70-0, name is Phenyl methacrylate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. name: Phenyl methacrylate

Example 7 2.5 mL of tetrahydrofuran solution of 3.0 mol/L concentration of methylmagnesium chloride was added to 10 mL of anhydrous tetrahydrofuran in a reaction vessel under an atmosphere of argon, and then 1.0 g of 3,3,5-trimethylcyclohexanone was added with stirring while the mixture in the reaction vessel was kept at a temperature of 50 C. or less, followed by stirring for another one hour at the same temperature with stirring. Then, 1.20 g of phenyl methacrylate was added drop wise into the reaction vessel, and then 1.74 g of N,N,N’,N’-tetramethylethylene diamine, and the reaction was carried out with stirring for 24 hours at a temperature of 60 C. After the reaction, an aqueous saturated solution of ammonium chloride was added to the resulting reaction mixture, and the desired product was extracted with ethyl acetate. The obtained organic layer was subjected to gas chromatographic analysis. As a result, the yield of 1,3,3,5-tetramethylcyclohexyl methacrylate was found to be 18.0 mol %.

The synthetic route of 2177-70-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; HONSHU CHEMICAL INDUSTRY CO., LTD.; US2006/167305; (2006); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 106685-41-0, 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 106685-41-0 as follows.

A round-bottom flask is loaded with adapalene methyl ester (7 g; 16.41 mmol), THF (42 ml), water (7 ml) and a 50% w/w sodium hydroxide aqueous solution (1.44 g; 18.05 mmol). The mixture is refluxed for 6 hours, then added with water (133 ml) and THF is distilled off to a residual content of approx. 5% w/w, heated to a temperature of about 80C until complete dissolution of the solid, then cooled to 15C. The crystallized product is filtered and dried under vacuum in a static dryer at a temperature of 50C, thereby obtaining adapalene sodium salt (6.7 g; 15.42 mmol) in 94% yield.

According to the analysis of related databases, 106685-41-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Dipharma S.p.A.; Lundbeck Pharmaceuticals Italy S.P.A.; EP1707555; (2006); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

3697-68-5, name is Ethyl 1-(hydroxymethyl)cyclopropanecarboxylate, 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. Formula: C7H12O3

REFERENCE EXAMPLE 1 Preparation of 2-bromomethylcyclopropanecarboxylic acid ethyl ester (2-formyl)cyclopropanecarboxylic acid ethyl ester (14.2 g, 0.10 mol) was dissolved in methanol (200 ml). The solution was cooled to 0 C., and sodium borohydride (3.8 g, 0.10 mol) was added. The mixture was stirred for 20 minutes. After distilling off the solvent, a saturated sodium chloride aqueous solution was added thereto. The product was extracted with chloroform, then dried and concentrated. Then, it was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to obtain (2-hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (14.3 g, yield: 99%). The (2-hydroxymethyl)cyclopropanecarboxylic acid ethyl ester (14.3 g, 0.1 mol) was dissolved in N,N-dimethylformamide (150 ml), and triphenylphosphine (25.9 g, 0.1 mol) was added thereto at room temperature. The mixture was stirred for 10 minutes. After cooling the mixture to 20 C., bromine (15.8 g, 0.1 mol) was dropwise added thereto over a period of 10 minutes. One hour later, the reaction mixture was added to a saturated sodium hydrogen carbonate solution, and the product was extracted with ethyl ether. It was dried, concentrated and then purified by column chromatography (hexane:ethyl acetate=5:1) to obtain (2-bromomethyl)cyclopropane carboxylic acid ethyl ester (15.3 g, yield: 74%). 1 NMR(CDCl3) delta0.9-1.0(m, 1H), 1.27(t, J=7.6 Hz, 3H), 1.3-1.5(m, 1H), 1.6-1.7(m, 1H, 1.8-2.0(m, 1H), 3.3-3.4(m, 2H), 4.25(q, J=7.6 Hz, 2H)

The synthetic route of 3697-68-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Asahi Glass Company, Ltd.; US5416231; (1995); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 37466-90-3, 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. 37466-90-3, name is Ethyl 3,4-diaminobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Step B: Preparation of 1H-benzo[d]imidazole-6-carboxylic acid ethyl ester 40 g of 3,4-diaminobenzoic acid ethyl ester (0.22 mol) and 200 mL formic acid were added to a three-necked bottle. After refluxing for 7 h, the reaction was completed. After concentration under reduced pressure, the ice water was poured into the residual solution. The resulting mixture was adjusted to pH 7 with sodium hydroxide. After sucking filtration, the filtrate was extracted with dichloromethane thrice, dried with anhydrous sodium sulfate, and decolored with active charcoal. Then the solution was concentrated under reduced pressure to get a white solid (29.6g). Yield: 70.2%. MS: 191 (M+1)

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 3,4-diaminobenzoate, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Shenyang J & Health Pharmaceutical Co., Ltd.; EP2468730; (2012); 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. 205448-64-2, name is Methyl 4-(((2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl)amino)-2-methoxybenzoate, A new synthetic method of this compound is introduced below., Safety of Methyl 4-(((2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl)amino)-2-methoxybenzoate

After heating biphenylphenoxybenzene (360 mL) to 175 C, Compound 3 (30 g, 89.47 mmol, 1 eq) was added portionwise at 175 C over 20 min. Stirring was continued at 175 C for another 2 h. The reaction mixture was cooled to room temperature (l6C), and petroleum ether (500 mL) was added. The resulting solid was filtered, and the filter cake washed with 100 mL of methyl tertiary butyl ether, dried under vacuum, and purified by flash silica gel chromatography (ISCO; 120 g SepaFlash Silica Flash Column, Eluent of 0-10% CH30H/CH2Cl2 50 mL/min) to give Compound 4 as a yellow solid (6 g, 27.3% yield). NMR (400 MHz, DMSO-d6) delta 11.70 (br s, 1H), 8.43 (s, 1H), 7.86 (br d, 1H), 7.02 (s, 1H), 5.99 (d, 1H), 3.89 (s, 3H), 3.81 (s, 3H); MS (El) for C12H11NO4, found 233.9 (MH+).

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; EXELIXIS, INC.; BANNEN, Lynne Canne; BUI, Minna; JIANG, Faming; WANG, Yong; XU, Wei; (235 pag.)WO2019/148043; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Electric Literature of 927-68-4, A common heterocyclic compound, 927-68-4, name is 2-Bromoethyl acetate, molecular formula is C4H7BrO2, 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.

EXAMPLE 50; 2-(Acetyloxy)ethyl 1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-3-(2-thienyl)-1,6- dihydropyridazine-4-carboxylate; A mixture of the title product of Preparation 35 (0.15g, 0.42 mmol), potassium carbonate (0.17g, 12.63 mmol) and 2-bromoethylacetate (77.2 mg, 0.46 mmol) in dimethylformamide (4 ml) were heated at 50C for 4h. Once at room temperature, solvent was evaporated under reduced pressure and the residue was purified by flash chromatography (CH2CI2:MeOH 99: 1 as eluent). 0.13 g (68%) of the desired final product were isolated. m. p.: 161.0-161.6C No. (DMSO-d6): 1.4 (t, J=7.0 Hz, 3 H) 1.9 (s, 3 H) 2.2 (s, 2 H) 3.4 (m, 3 H) 3.9 (m, 2 H) 4.2 (q, J=7.0 Hz, 2 H) 7.0 (m, 2 H) 7.3 (d, J=5.0 Hz, 1 H) 7.6 (d, J=5.0 Hz, 1 H) 8.3 (s, 1 H) 8.3 (d, J=5.0 Hz, 1 H) 9.0 (s, 1 H)

The synthetic route of 927-68-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ALMIRALL PRODESFARMA, S.A.; WO2005/123693; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Application of 69812-51-7, 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. 69812-51-7, name is Methyl 4-chlorosulfonylbenzoate, This compound has unique chemical properties. The synthetic route is as follows.

Preparation 102; 4-(3-Cyclopentyl-indazole-1-sulfonyl)-benzoic acid methyl ester; Combine 3-Cyclopentyl-lH-indazole (2.168 g 11.640 mmole) with triethylamine (3.526g, 34.92 mmoles) in 50 mls of dichloromethane. Dissolve 4- Chlorosulfonyl-benzoic acid methyl ester (4.085g, 17. 460mmole) in dichloromethane 50ml and add drop wise to solution at 0 C. Stir the reaction is for 12 hrs. Dilute the reaction and wash with NaHC03. Dry organic layer over MgS04 and concentrate. Purify the residue via column chromatography with a mixture of ethyl acetate and hexanes to isolate 2.046g (Yield=48. 5%) of the title compound: MS ES+385.3.

The chemical industry reduces the impact on the environment during synthesis Methyl 4-chlorosulfonylbenzoate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/66126; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Reference of 50413-30-4, 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 50413-30-4 as follows.

To a stirred solution of compound If-I (7 g, 38.6 mmol) in pyridine (80 ml) was slowly added TsCI (8.8 g, 46.6 mmol) at rt. This solution was further stirred for 16h. The reaction mixture was poured into cold water upon which a solid was formed. The precipitate was filtered off and washed with n-pentane (50 ml) to afford the title compound If-2 as an off-white solid (10.8 g, 70% yield). LCMS [M+H] 336.

According to the analysis of related databases, 50413-30-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ONTARIO INSTITUTE FOR CANCER RESEARCH (OICR); AL-AWAR, Rima; MAMAI, Ahmed; (134 pag.)WO2019/119141; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 28868-76-0, name is Dimethyl 2-chloromalonate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. name: Dimethyl 2-chloromalonate

To 8.33 g of dimethyl chloromalonate, 10.7 ml of 7N ammonia/methanol solution was dropped at 0C and then stirred for 10 minutes. The reaction mixture was further stirred at room temperature for 2 hours, filtered and concentrated. The residue was dissolved with a mixed solvent of chloroform with methanol. The solution was filtered, and then concentrated. The residue was subjected to silica gel column chromatography to give 4.4 g of methyl 2-chloro-2-carboxamideacetate. Mp. 79.5C1H-NMR (300 M Hz, CDCl3, TMS delta (ppm) ) : 3.86 (s, 3H), 4.79 (s, 1H), 5.8-6.0 (bs, 1H), 6.5-6.7 (bs, 1H)

The synthetic route of 28868-76-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Sumitomo Chemical Company, Limited; EP1422227; (2004); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics