Month: March 2021

Electric Literature of 645-36-3, These common heterocyclic compound, 645-36-3, name is 2,2-Diethoxyethanamine, 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.

Compound 3 was prepared by the condensation of commercially available aminoacetaldehyde diethyl acetal with the phthalic anhydride (1:1 mol ratio), using toluene under reflux, in the presence of a catalytic amount of DMAP (yield 52%) for 2 h. In the next step, 2-(2,2-diethoxyethyl)isoindoline-1,3-dione (3) underwent acid hydrolysis (sulphuric acid at 70%) in reflux for 2 h. After the reaction was completed, it was allowed to reach at room temperature and was then cooled to induce precipitation. The formed precipitate was filtered on a sintered funnel with distilled water, yielding 55% of the pure product. For the synthesis of 5a and 5b, 2-(1,3-dioxoisoindol-2-yl) acetaldehyde (4) reacted with thiosemicarbazide (in the ratio 1:1) (for 5a) or 4-phenyl-3-thiosemicarbazide (for 5b), in ethanol, under reflux with catalytic amount of HCl (4 drops) for 4 h. The reactions were followed by thin layer chromatographic plate analysis. The formed precipitate was filtered on a sintered funnel with ethanol to yield the pure product (yield 76% for 5a and 70% for 5b).

Statistics shows that 2,2-Diethoxyethanamine is playing an increasingly important role. we look forward to future research findings about 645-36-3.

Reference:
Article; De Moraes Gomes, Paulo Andre Teixeira; Oliveira, Arsenio Rodrigues; De Oliveira Cardoso, Marcos Verissimo; De Farias Santiago, Edna; De Oliveira Barbosa, Miria; De Siqueira, Lucianna Rabelo Pessoa; Moreira, Diogo Rodrigo Magalhaes; Bastos, Tanira Matutino; Brayner, Fabio Andre; Soares, Milena Botelho Pereira; De Oliveira Mendes, Andresa Pereira; De Castro, Maria Carolina Accioly Brelaz; Pereira, Valeria Rego Alves; Leite, Ana Cristina Lima; European Journal of Medicinal Chemistry; vol. 111; (2016); p. 46 – 57;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Application of 64115-88-4,Some common heterocyclic compound, 64115-88-4, name is 1-Bromo-2-(trifluoromethoxy)benzene, molecular formula is C7H4BrF3O, 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 microwave vial with stir bar was added 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(3,4,5-trimethoxyphenyl)benzo[d]oxazol-2-amine (97 mg, 0.228 mmol), 4-bromo-1H-benzo[d]imidazole (30 mg, 0.152 mmol), DME (1.5 mL), Sodium carbonate (0.76 mL, 1.523 mmol) [2.0M (aq)] and PdCl2(dppf)-CH2Cl2 adduct (12.43 mg, 0.015 mmol). Vial capped and heated in an aluminum tray at 120 C for 3 hr. Reaction mixture was cooled to RT, diluted with water. Aqueous mixture was extracted with EtOAc. Organic phases combined, washed with brine, dried (Na2SO4), filtered and concentrated. Residue dissolved with DMSO and purified by RHPLC. Product fractions combined, frozen and lyophilized to afford a TFA salt of 7-(1H-benzo[d]imidazol-4-yl)-N-(3,4,5-trimethoxyphenyl) benzo[d]oxazol-2-amine (8.1 mg, 0.015 mmol, 9.93 % yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1-Bromo-2-(trifluoromethoxy)benzene, its application will become more common.

Reference:
Article; Costales, Abran; Mathur, Michelle; Ramurthy, Savithri; Lan, Jiong; Subramanian, Sharadha; Jain, Rama; Atallah, Gordana; Setti, Lina; Lindvall, Mika; Appleton, Brent A.; Ornelas, Elizabeth; Feucht, Paul; Warne, Bob; Doyle, Laura; Basham, Stephen E.; Aronchik, Ida; Jefferson, Anne B.; Shafer, Cynthia M.; Bioorganic and Medicinal Chemistry Letters; vol. 24; 6; (2014); p. 1592 – 1596;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 64465-53-8, name is 4-Fluoro-3-methoxyaniline, A new synthetic method of this compound is introduced below., Quality Control of 4-Fluoro-3-methoxyaniline

Dissolve 4-fluoro-3-methoxyphenylamine (5. 0 g, 35 mmol) in water (25 mL) and concentrated sulfuric acid (8 mL). Cool to less than 0 C in an ice/methanol bath and add sodium nitrite (2. 7 g, 39 mmol) dropwise in a solution in water (20 mL) and stir one h. Dissolve potassium iodide (9. 9 g, 60 mmol) in water (35 mL) and add dropwise. Warm to room temperature and stir 18 h. Extract with ethyl acetate (300 mL), wash with water (200 mL), saturated aqueous sodium thiosulfate (300 mL), and saturated aqueous sodium chloride (300 mL). Dry (sodium sulfate), filter, and concentrate to give the title compound as an orange oil (8. 8 g, 99%). H NMR (300 MHz, CDCl3) 6 3. 88 (s, 3H), 6. 77-6. 87 (m, 1H), 7. 16-7. 26 (m, 2H).

The synthetic route of 64465-53-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/94822; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 651734-54-2, name is 2,6-Difluoro-3,5-dimethoxyaniline, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C8H9F2NO2

TEA (0.15mL) was added to a solution of 6-chloro nicotinic acid (0.12g, 0.79 mmol) in DMF (2mL) followed by the addition of T3P (0.67mg, 1.0 mmol). Stirred the reaction mass for 10 min. and added 2,6-difluoro-3,5-dimethoxyaniline (O. lg, 0.52mmol). Continued the stirring with heating at 100 C for 24h. Quenched the reaction mass with ice cold water and the solid separated is filtered, dried under vacuum to afford desired title compound (0.14g, 80%). LCMS: m/z = 329.0 (M+H)+.

According to the analysis of related databases, 651734-54-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; EISAI R & D MANAGEMENT CO., LTD.; REYNOLDS, Dominic; HAO, Ming-Hong; WANG, John; PRAJAPATI, Sundeep; SATOH, Takashi; SELVARAJ, Anand; (128 pag.)WO2016/164703; (2016); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 701-56-4, name is 4-Methoxy-N,N-dimethylaniline, belongs to ethers-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 701-56-4, name: 4-Methoxy-N,N-dimethylaniline

General procedure: Under an atmosphere of N2, KOt-Bu (2.2 mmol), dioxane (0.9 mL), DMSO (1.65 mmol), tertiary amine 1 (0.55 mmol), and aryl halide 2(1.65 mmol) were successively added to a Schlenk reaction tube. The mixture was stirred vigorously at 80-120 C for 12 h. Then the mixture was diluted with EtOAc, washed with sat. brine, and dried (anhyd Na2SO4). Then the solvent was removed under reduced pressure and the residue was purified by flash column chromatography (petroleum ether and petroleum ether-EtOAc, 100:1 for the methoxy group derived products) to give pure products 3.

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, 4-Methoxy-N,N-dimethylaniline, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Huang, Pei; He, Bang-Yue; Wang, Hui-Min; Lu, Jian-Mei; Synthesis; vol. 47; 2; (2015); p. 221 – 227;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 10103-06-7, name is 2,3-Dimethoxynaphthalene belongs to ethers-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Product Details of 10103-06-7

EXAMPLE 1; 2-(l-(6,7-bis(difluoro methoxy)naphthalen-2-yl)-2-methylpropyl)-2H-tetrazole (1)To a stirred solution of A (40 g, 0.21 mol) in CH2CI2 (600 mL) was added isobutyryl chloride (34 mL, 0.31 mol) at -5 C, followed by portion- wise addition of AICI3 (56.8 g, 0.42 mol) over a period of 20 min under N2 atmosphere. The reaction was allowed to slowly warm to RT and stirred for 3h; the reaction mixture was poured into ice-cold water (200 mL) and the organic layer was separated. The aqueous layer was then extracted with CH2CI2 (2 x 100 mL); combined organic extracts were washed with 5% NaHC03 solution (100 mL), water (100 mL), brine (100 mL) and dried over anhydrous Na2S04. After filtration and evaporation under reduced pressure, the crude material was washed with w-hexane to afford B (35 g, 0.13 mol, 63%) as off-white solid. 1H NMR (200 MHz, CDC13): delta 8.34 (s, 1 H), 7.90 (dd, / = 8.6,1.8 Hz, 1 H), 7.73 (d, / = 8.6 Hz, 1 H), 7.26 (s, 1 H), 7.14 (s, 1 H), 4.03 (s, 6 H), 3.79-3.63 (m, 1 H), 1.27 (d, / = 7.0 Hz, 6H). MS (ESI): mlz 259 [M+H]+.To a stirred solution of B (18 g, 69 mmol) in CH2C12 (180 mL) was added BBr3 (87.2 g, 348 mmol) drop wise at -40 C. After completion of addition, stirring was continued for addition 1 h at -40 C and 1 h at RT. The reaction mixture was poured into cold water and aqueous layer was then extracted with CH2CI2 (2 x 200 mL). Combined organic extracts were washed with water (100 mL), brine (100 mL) and dried over anhydrous Na2S04. After filtration and evaporation of solvent under reduced pressure, the crude material was purified by column chromatography (Si02, 100-200 mesh) to afford C (9.0 g, 39 mmol, 56%) as brown color solid. 1H NMR (200 MHz, CDC13): delta 8.29 (s, 1 H), 7.88 (dd, / = 8.8, 1.6 Hz, 1 H), 7.68 (d, / = 8.6 Hz, 1 H), 7.36 (s, 1 H), 7.26 (s, 1 H), 5.88 (br s, 2 H), 3.79-3.63 (m, 1 H), 1.27 (d, / = 6.8 Hz, 6 H).To a stirred solution of C (10.0 g, 0.043 mol) in DMF (100 mL) were added sodium 2-bromo-2,2- difluoroacetate (42.6 g, 0.21 mol) (the Na salt was prepared by treating ester with 1.0 eq of NaOH in EtOH: H20 (2:1) at RT for 16. Then solvent was evaporated and residue was co-distilled with toluene (3 times) to obtain the salt.) and K2C03 (36 g, 0.26 mol) and the mixture was stirred at 80- 90 C for 48 h. The reaction mixture was poured into cold water and aqueous layer was then extracted with CH2C12 (3 x 100 mL). Combined organic extracts were washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2S04. After filtration and evaporation of solvent under reduced pressure, the crude material was purified by column chromatography (Si02, 100- 200 mesh) to afford D (3.0 g, 0.009 mol, 21%) as a solid. 1H NMR (500 MHz, CDC13): delta 8.40 (s, 1 H), 8.05 (dd, / = 8.5, 1.5 Hz, 1 H), 7.86 (d, / = 9.0 Hz, 1 H), 7.79 (s, 1 H), 7.68 (s, 1 H), 6.67 (t, JF.H = 73 Hz, 1 H), 6.65 (t, JF>H = 73 Hz, 1 H), 3.72-3.65 (m, 1 H), 1.27 (d, / = 7.0 Hz, 6 H). To a stirred solution of D (0.65 g, 1.96 mmol) in MeOH (10 mL) was added NaBH4 (0.15 g, 3.9 mmol) at 0 C and the resulting mixture was stirred for additional 30 min at 0 C. The reaction mixture was quenched with ice-cold water and the aqueous layer was then extracted with EtOAc (2 x 50 mL). Combined organic extracts were washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude material was purified by column chromatography (Si02, 100-200 mesh) using gradients of EtOAc/hexane to afford E (0.58 g, 1.74 mmol, 89%) as a semi solid. 1H NMR (200 MHz, CDC13): delta 7.80-7.72 (m, 2 H), 7.64 (s, 2 H), 7.50 (dd, / = 8.4, 1.8 Hz, 1 H), 6.63 (t, JF>H = 72 Hz, 2 H), 4.58-4.53 (m, 1 H), 2.10-2.00 (m, 1 H), 1.95 (d, / = 3.0 Hz, 1 H), 1.00 (d, / = 6.8 Hz, 3 H), 0.84 (d, / = 6.8 Hz, 3 H).To a stirred solution of E (0.8 g, 2.4 mmol) in acetonitrile (15 mL) was added thionyl chloride (0.27 mL, 3.61 mmol) at 0 C and the resulting reaction mixture was stirred for additional 30 min at 0 C. The reaction mixture was quenched with water (20 mL) and the aqueous layer was then extracted with EtOAc (3 x 50 mL). The combined organic extracts were washed with 5% NaHC03 solution (50 mL), water (50 mL), brine (50 mL), dried over anhydrous Na2S04 and concentrated under reduced pressure to afford F (0.8 g, 2.28 mol, 95%) as solid. 1H NMR (200 MHz, CDCI3): delta 7.81-7.72 (m, 2 H), 7.65 (s, 2 H), 7.53 (dd, / = 8.6,1.8 Hz, 1 H), 6.62 (t, JF>H = 74 Hz, 2 H), 4.75 (d, / = 8.0 Hz, 1 H), 2.38-2.28 (m, 1 H), 1.14 (d, / = 6.4 Hz, 3 H), 0.87 (d, / = 6.8 Hz, 3 H).To a stirred solution of F (0.3 g, 0.85 mmol) in DMF (5 mL) were added K2C03 (0.47 g, 3.41 mmol) and IH-tetrazole (0.18 g, 2.56 mmol) at RT. The reaction mixture was heated at 90 C for 36 h. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2 x 50 mL); combined organic extracts were washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2S04. After filtration and evaporation of solvent under reduced pressure, the crude mater…

The synthetic route of 10103-06-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; VIAMET PHARMACEUTICALS, INC.; HOEKSTRA, William, J.; SCHOTZINGER, Robert, J.; RAFFERTY, Stephen, William; WO2011/82245; (2011); A2;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Reference of 22483-09-6,Some common heterocyclic compound, 22483-09-6, name is 2,2-Dimethoxyethanamine, molecular formula is C4H11NO2, 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: Benzaldehyde derivatives (1500 mg, 13.13 mmol) and Aminoacetaldehyde dimethyl acetal (19.70 mmol) were dissolved in 15 mL of methanol, NaBH(OAc)3 (19.70 mmol) was added at 0 C slowly in 3h. The reaction mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was extracted with dicloromethane (DCM, 15 mL) three times, and the combined extracts were washed with 2N KOH, brine and dried over Na2SO4. The solution was filtered and added TEA (39.40 mmol) and TsCl (21.00 mmol) at 0C and stirred at room temperature for 5h. The resulting mixture was extracted with DCM (15 mL) three times. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel flash column chromatography (PE : EA = 5:1) to give the desired product.

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

Reference:
Article; Shi, Zeyu; Xiao, Qiong; Yin, Dali; Chinese Chemical Letters; (2019);,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 17715-69-4, 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 17715-69-4 as follows.

General procedure: A suspension of Pd2(dba)3 (6.9 mg, 0.0075 mmol), tBu3PHBF4 (8.7 mg,0.03 mmol), KOH (42 mg, 0.75 mmol), aryl bromide 9 (0.36 mmol) and tetralone 10(0.3 mmol) in a mixture of dioxane/water (4:1, v/v, 3 mL) was degassed and heated under Ar and microwave irradiation (80W of initial power, 100 ¡ãC, 40min, infrared probe). Then, the mixture was allowed to cool to rt, diluted in AcOEt, washed with saturated NH4Cl solution, dried over anhydrous Na2SO4,filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography.

According to the analysis of related databases, 17715-69-4, the application of this compound in the production field has become more and more popular.

Reference:
Article; Manvar, Dinesh; Fernandes, Talita De A.; Domingos, Jorge L.O.; Baljinnyam, Erdenechimeg; Basu, Amartya; Junior, Eurides F.T.; Costa, Paulo R.R.; Kaushik-Basu, Neerja; European Journal of Medicinal Chemistry; vol. 93; (2015); p. 51 – 54;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Synthetic Route of 82830-49-7, A common heterocyclic compound, 82830-49-7, name is 2-Fluoro-1,4-dimethoxybenzene, molecular formula is C8H9FO2, 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.

General procedure: To an oven-dried round-bottom flask with a stir bar were charged with a solution of secondary amines 2 (1.5 mmol) in 1 mLdry THF at room temperature under an argon atmosphere. To thissolution was slowly added 1.2 mL nBuLi (2.5 mol/L in n-hexane,3.0 mmol) via syringe. After stirring at 25 C for 10 min, a solution of fluoroarene 1 (1.0 mmol) in 1mL dry THF was added to the reaction flask. The reaction mixture was stirred for 0.5 h at 25 C, and then quenched with 2 mL saturated aqueous solution of NaCl and extracted with H2O (20 mL) and ethyl acetate (3 20 mL). The organic layer was separated and dried with anhydrous Na2SO4, filtered, and evaporated under vacuum. The crude product was purified by column chromatography on silica gel using a petroleum ether/ethyl acetate mixture as eluent to afford the pure target compounds.

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:
Article; Lin, Yingyin; Li, Meng; Ji, Xinfei; Wu, Jingjing; Cao, Song; Tetrahedron; vol. 73; 11; (2017); p. 1466 – 1472;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 109-85-3, name is 2-Methoxyethylamine, belongs to ethers-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 109-85-3, Application In Synthesis of 2-Methoxyethylamine

To a stirred solution of tert-butyl 4-oxopiperidine-l -carboxylate (2 g, 10.04 acetic acid (0.575 mL, 10.04 mmol) and 2-methoxyethanamine (0.754 g, 10.04 mmol) in MeOH (40 mL) under N2 was cooled to 0 C. Then the mixture was added NaCNBH4 (0.631 g, 10.04 mmol) and stirred at RT for 16 hrs. The reaction mixture was quenched with 50 mL of aqueous 10% NaHC03 solution and extracted with EtOAc (2 x 200 mL). The combined organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography gave 103 A (liquid, 1.5 g, 5.81 mmol, 58 % yield). GC-MS Anal.Calc?d for C]3H26N203 258.2, found 157.2 (M- Boc). Tr = 9.43 min (Method AE).

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, 2-Methoxyethylamine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; BALOG, James Aaron; MARKWALDER, Jay A.; SHAN, Weifang; WILLIAMS, David K.; NARA, Susheel Jethanand; ROY, Saumya; THANGAVEL, Soodamani; CHERUKU, Srinivas; SISTLA, Ramesh Kumar; (230 pag.)WO2020/23355; (2020); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem