Month: November 2020

A common heterocyclic compound, 178312-47-5, name is Ethyl 4,4-difluorocyclohexanecarboxylate, molecular formula is C9H14F2O2, 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. 178312-47-5.

Synthesis of Compound 349: To a solution of the ethyl ester (349A; 10 g; 0.052 mol.) in diethyl ether (50 ml) at-78 C (bath temp. ) was added KHMDS (0.5 M in toluene ; 156.087 ml ; 1.5 equiv. ). The resulting solution was stirred for 30 minutes, then benzyl chloromethyl ether (11.89 ml ; density 1.13 ; 1.65 equiv. ) was added. The reaction mixture was stirred at-78 C to R. T. for 24 h. Reaction was stopped by addition of saturated aq. NH4C). It was then diluted with ethyl acetate and the combined organic phase was washed with brine, dried over Na2SO4 and evaporated to dryness in vacuo to provide a light brown oil (24.2 g). It was chromatographed over silica gel (300 g). The column was eluted with 1 %- 4% ethyl acetate in n-hexane providing in some of the fractions pure 349B (6.54 g).

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

Reference:
Patent; SCHERING CORPORATION; WO2005/87731; (2005); A1;,
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46004-37-9, 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. 46004-37-9, name is Methyl 4-amino-2-chlorobenzoate, A new synthetic method of this compound is introduced below.

To a solution of methyl 2-chloro-4-aminobenzoate (109 g, 587 mmol) in 440 mL DMF was added NaIO4 (50 g) and iodine (119 g). The mixture was warmed at 50 C. for 2 h. It was then cooled and diluted with water and filtered. The solid was treated with sodium hydrogensulfite (19 g) in water (110 mL) at 40 C. for 1 h. The mix was filtered again and washed with water, followed by isopropanol. Upon drying, the product was obtained in 56% yield. M+H+(312).

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; Chakravarty, Sarvajit; Dugar, Sundeep; Lu, Qing; Luedtke, Gregory R.; Mavunkel, Babu J.; Perumattam, John J.; Tester, Richland W.; US2004/142940; (2004); A1;,
Ester – Wikipedia,
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106-32-1,Some common heterocyclic compound, 106-32-1, name is Ethyl octanoate, molecular formula is C10H20O2, 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: To a solution of 1,1,2,2,3,3,4,4,5,5,6,6,6-tridecafluorohexyl iodide (0.22 mL, 1.0 mmol), ethyl benzoate (0.16 mL, 1.1 mmol) in Et2O (3 mL) was added at -80C methyllithium (1.5 M in Et2O with lithium bromide; 0.73 mL, 1.1 mmol) and stirring was continued for 30 min at the same temperature where diethyl-aluminium chloride (1 M in n-hexane; 1.1 mL, 1.1 mmol) was gradually added and further stirring for 15 min at -80 C. In a separate flask, lithium bromide (0.12 g, 1.4 mmol), triethyl phosphonoacetate (0.26 mL, 1.3 mmol), and THF (1 mL) was mixed at 0 C where triethylamine (0.19 mL, 1.4 mmol) was added and the solution was stirred for 10 min at room temperature. This mixture was slowly introduced to an aluminium acetal solution prepared above with the aid of cannula and the whole mixture was further stirred for 1 h at room temperature. To this solution were successively added Et2O (3 mL), NaF (0.185 g, 4.4 mmol) and H2O (59 mg, 3.3 mmol), which was stirred for 0.5 h at room temperature. Filtration with a pad of silica gel and concentration furnished a crude mixture which was purified by silica gel column chromatography (n-hexane:CH2Cl2=6:1) to afford 0.484 g (0.979 mmol, 98% yield, E_Z=>99:1) of the title compound 5ca as a colourless oil.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 106-32-1, its application will become more common.

Reference:
Article; Yamazaki, Takashi; Mano, Noriko; Hikage, Reo; Kaneko, Tsutomu; Kawasaki-Takasuka, Tomoko; Yamada, Shigeyuki; Tetrahedron; vol. 71; 42; (2015); p. 8059 – 8066;,
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 40546-94-9 as follows. 40546-94-9

A reaction mixture of 0.75 kg 3,4-dihydro-6-methyl -4-phenyl-2H-benzopyran-2-one, 0.262 kg sodium hydroxide and 0.93 L DM water was stirred at 60-650C for 2 hrs. The reaction was cooled to RT. 0.825 kg dimethylsulphate was added drop wise to reaction mixture within 1 hr. After the completion of addition, reaction mixture was stirred at same temperature for 2 hrs. Again solution of 0.186 kg sodium hydroxide in 0.93 L DM water was added at RT within 1 hr. The reaction mixture was stirred at 800C for 4 hrs. After completion of reaction, reaction was cooled to RT. 0.3 L Cone, hydrochloric acid was added drop wise to the reaction mixture till washing is neutral. The reaction mixture was stirred for 2 hrs, then filtered & washed with 2.0 L DM water to obtain wet cake. The wet cake was dried at 60-650C for 10-12 hrs to obtain 3-(2-methoxy-5-methylphenyl)-3-phenyl propionic acid (Yield: 0.71 kg, 83%).[159] HPLC Purity: > 95 %.

According to the analysis of related databases, 40546-94-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ALEMBIC LIMITED; PONNAIAH, Ravi; DESAI, Sanjay; SHAH, Chankrakant Chunilal; PATEL, Kalpesh Shantibhai; PAREKH, Viral Maheshbhai; WO2010/46801; (2010); A2;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

89-91-8, 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. 89-91-8, name is Methyl 2,2-dimethoxyacetate, A new synthetic method of this compound is introduced below.

Step 1 : Preparation of 1-(2,4-dichloropyridin-3-yl)-2,2-dimethoxyethan-1-one . A cold (-78 C) solution of 2,4-dichloro-3-iodopyridine (2.73 g, 9.968 mmol) in THF (49.84 mL) was treated dropwise with 2.5 M n-BuLi in hexanes (4.785 mL, 11.96 mmol). After stirring for 20 min at -78 C, the reaction mixture was treated dropwise with methyl 2,2-dimethoxyacetate (1.708 mL, 13.95 mmol). The resulting mixture was stirred for 1 h at -78 C, before quenching with saturated NH4Cl(aq) (10 mL). The quenched mixture was allowed to warm to ambient temperature. Subsequently, the mixture was diluted with water (30 mL), and extracted with EtOAc. The organic extracts were dried over anhydrous Na2S04(S>, filtered, and concentrated in vacuo. The crude residue was purified by silica chromatography (0-30% EtOAc in hexanes) to afford the title compound (1.9 g, 76%).

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; ARRAY BIOPHARMA INC.; WALLS, Shane M.; REN, Li; RAMANN, Ginelle A.; MORENO, David A.; METCALF, Andrew T.; MCFADDIN, Elizabeth A.; KOLAKOWSKI, Gabrielle R.; BLAKE, James F.; DAI, Donghua; HAAS, Julia; JIANG, Yutong; KAHN, Dean; (368 pag.)WO2019/143994; (2019); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

4897-84-1, Adding some certain compound to certain chemical reactions, such as: 4897-84-1, name is Methyl 4-bromobutanoate, 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 4897-84-1.

To a 250 mL flask equipped with a magnetic stirring bar, azepane, anhydrous acetonitrile (20 mL), methyl-4-bromobutyrate and potassium carbonate were added. A slight temperature increase was observed. The mixture was stirred at room temperature and the overall reaction time was 4 days. (0049) As the reaction proceeded, potassium carbonate was gradually consumed as it scavenged the liberated HBr to form potassium bromide (4.8 g) and potassium bicarbonate (4.0 g). (0050) DCM (10 mL) was added and the solid was collected by vacuum filtration. The organic phase was washed with deionized water (10 mL), separated, dried over MgSO4 and filtered, and the solvent was stripped using rotary evaporation. Yield: pale oil, 7.9 g, (>99percent). (0051) Characterization. FTIR: C?O, 1737, C?O, 1177 cm?1. (0052) H+ NMR: (CDCl3) delta ppm 3.67 (s, 3H), 2.61 (t, 4H), 2.48 (t, 2H), 2.34 (t, 2H), 1.77 (q, 2H), 1.62-1.58 (m, 8H).

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 4897-84-1.

Reference:
Patent; NOHMs Technologies, Inc.; Moganty, Surya; Abbate, Luigi; Torres, Gabriel; Brown, Kevin; Sinicropi, John; (13 pag.)US2017/305869; (2017); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

35180-01-9, 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. 35180-01-9, name is Chloromethyl isopropyl carbonate, A new synthetic method of this compound is introduced below.

400 ml of ethanol, 50 ml of dimethylacetamide and 40 g of tenofovir monohydrate were added to a 1000 ml reaction flask,Stirring, control the temperature of 20 C dropwise add 85g of N, N-diisopropylethylamine, drop finished to continue dropping 100g chloromethyl carbonateThe reaction system was heated to 50 C for 8 hours and the monoester was detected to be less than 10%. The reaction solution was concentrated under 40 C under reduced pressure until no liquid flowed out and concentrated to the residue 500 ml of ethyl acetate, 200 ml of a 6% solution of sodium hydrogencarbonate,After stirring, the layers were extracted and the organic phase was washed twice with 200 ml of purified water,The obtained organic phase was dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure,The resulting concentrated residue was used directly in the next step.

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; Suzhou Homesun Pharmaceutical Co., Ltd.; Fan, chao; (7 pag.)CN105418683; (2016); A;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 61367-07-5, name is Methyl trans-4-aminocyclohexanecarboxylate hydrochloride, I believe this compound will play a more active role in future production and life. 61367-07-5

(1) Methyl trans-4-aminocyclohexanecarboxylate hydrochloride (47.5 g) obtained in Reference Example 2(1), bis(2-chloroethyl)ether (34.5 ml), sodium carbonate (77.9 g) and sodium iodide (88 g) are suspended in a mixture of tetrahydrofuran (1400 ml) and N,N-dimethylacetamide (280 ml). The mixture is then heated under reflux for 18 hours. Bis(2-chloroethyl)ether (23 ml) and sodium iodide (22 g) are added to the reaction solution and the mixture is refluxed for additional 6 hours. The reaction solution is concentrated under reduced pressure. The residue is dissolved in ethyl acetate/water and the organic layer is separated. The organic layer is washed with water and saturated brine, dried over sodium sulfate and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (eluent: ethyl acetate/hexane = 1/30, subsequently by ethyl acetate/hexane = 1/5 followed by 1/3) to give methyl trans-4-morpholin-4-ylcyclohexane-carboxylate (53.9 g). APCI-MS M/Z:228[M+H]+.

The chemical industry reduces the impact on the environment during synthesis 61367-07-5. I believe this compound will play a more active role in future production and life.

Reference:
Patent; TANABE SEIYAKU CO., LTD.; EP1582521; (2005); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

252881-74-6, Adding some certain compound to certain chemical reactions, such as: 252881-74-6, name is tert-Butyl 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)propanoate, 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 252881-74-6.

A solution of 2-14 (280 mg, 1.01 mmol), tert-butyl 3-(2-(2-(2-aminoethoxy)ethoxy) ethoxy)propanoate (2-15 where n=3, 337 mg, 1.22 mmol) and DIEA (0.7 mL, 4.04 mmol) in DMF (5 mL) was stirred at 80 C for overnight. The resulting mixture was diluted with EtOAc and washed with water five times. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (DCM/EtOAc = 90 : 10 to 50 : 50) to afford 2-16 where n =3.

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 252881-74-6.

Reference:
Patent; DANA FARBER CANCER INSTITUTE, INC.; GRAY, Nathanael; JANG, Jaebong; DE CLERCQ, Dries; ECK, Michael; (201 pag.)WO2017/185036; (2017); A1;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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. 37746-78-4 name is (E)-Ethyl 4-bromobut-2-enoate, 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. 37746-78-4

General procedure: To a 50-mL round-bottomed flask were added ethyl pyrazole-5-carboxylate 1 (1.00 mmol), ethyl 4-bromobut-2-enoate 2 (2.00 mmol), potassium carbonate (0.28 g, 2.05 mmol) and C2H5OH (20 mL). The mixture was refluxed for 8 h. And then they were poured into water (100 mL) and extracted with CH2Cl2 (3 ¡Á 30 mL). The combined extracts were washed with water, dried over anhydrous Na2SO4 and filtered, and the solvent was removed by rotary evaporation. The crude products were purified by column chromatography to afford compounds 3a-f in 42-60%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, (E)-Ethyl 4-bromobut-2-enoate, and friends who are interested can also refer to it.

Reference:
Article; Yan, Peiling; Duan, Guiyun; Ji, Ruixue; Ge, Yanqing; Tetrahedron Letters; vol. 59; 25; (2018); p. 2426 – 2429;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics