Author: Jessica.F

Reference of 437-83-2,Some common heterocyclic compound, 437-83-2, name is 3-Fluoro-2-methoxyaniline, molecular formula is C7H8FNO, 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.

Hydrobromic acid (48% in water, 140 mL) is added slowly to an aliquot of 11 (14. 33 g, 101. 5 mmol) cooled to 0 C. The resulting solid is broken up with a glass rod and stirred vigorously at 0 C for 10 min. A solution of sodium nitrite (7. 40g, 107. 2 mmol) in water (50 mL) is added slowly (-1. 5 h) to the stirred slurry containing 3-fluoro-2- methoxyphenylamine and hydrobromic acid, maintaining the temperature of the reaction mixture below 5 C. A purple solution of cuprous bromide (9. 62 g, 67. 1 mmol) in hydrobromic acid (48% in water, 50 mL) is added dropwise to the reaction mixture, maintaining the temperature of the reaction mixture below 5 C. The resulting reaction mixture is heated at 60 C until the evolution of gas ceases (-2. 5 h). The reaction mixture is cooled to room temperature, and the product extracted with diethyl ether (6 x 150 mL). The combined organic extracts are washed with brine (3 x 150 mL), dried over magnesium sulfate, and evaporated under reduced pressure to give 1-BROMO-3-FLUORO-2-METHOXYBENZENE as a brown oil. This product is of sufficient purity (295% by NMR spectroscopy) to use directly in the next synthetic STEP. 1H NMR (CDCl3) : No.3. 95 (d, JH-F= 1.5 Hz, 3H, OCH3), 6. 88 (apparent t OF D, JH-H = 8. 0 Hz, JH-F = 5. 5 Hz, 1H, H-5), 7. 04 (ddd, JH-F = 10. 5 Hz, JH-H = 8. 0 HZ, JH-H = 1. 5 Hz, 1H, H-4), 7. 30 (d of apparent T, JH-H = 8. 0 Hz, JH-H = 1. 5 Hz, JH-F = 1. 5 Hz, 1H, H-6). I9F {LH} NMR (CDCl3) : S-127. 7 (s). 13C {IH} NMR (CDCl3) : 1561. 4 (d, JC-F= 5. 0 Hz, OCH3), 116. 2 (d, JC-F = 19. 5 Hz, C-4), 117. 7 (D, JC-F = 3. 0 Hz, C-1), 124. 5 (d, JC-F = 8. 0 Hz, C-5), 128. 5 (D, JC-F = 3. 5 Hz, C-6), 145. 7 (d, Jc-F = 12. 5 Hz, C-2), 156. 2 (d, JC-F = 250. 5 Hz, C-3).

The synthetic route of 437-83-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ACHILLION PHARMACEUTICALS, INC.; WO2005/19228; (2005); A1;,
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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. 104-92-7, name is 1-Bromo-4-methoxybenzene, A new synthetic method of this compound is introduced below., Application In Synthesis of 1-Bromo-4-methoxybenzene

General procedure: A mixture of Ni(cod)2 (0.050 mmol), SIPr·HCl (0.050 mmol),KOt-Bu (0.050 mmol), and CPME was stirred at 100 C for 30min. To this was added NaOAc (0.85 mmol), aryl bromide 1(0.50 mmol), and N-TMS-carbazole 2 (0.65 mmol). The reactionmixture was quenched with H2O. The aqueous layer wasextracted with Et2O and washed with brine. The combinedorganic layers were dried over anhydrous MgSO4. After concentrationin vacuo, the residue was purified by flash chromatographyon silica gel or preparative TLC to afford N-aryl-carbazoles 3.

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; Minami, Yasunori; Komiyama, Takeshi; Shimizu, Kenta; Uno, Shu-Ichi; Hiyama, Tamejiro; Goto, Osamu; Ikehira, Hideyuki; Synlett; vol. 28; 18; (2017); p. 2407 – 2410;,
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Synthetic Route of 5414-19-7,Some common heterocyclic compound, 5414-19-7, name is 1-Bromo-2-(2-bromoethoxy)ethane, molecular formula is C4H8Br2O, 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.

A solution of (1,3-dioxoisoindolin-2-yl)potassium (10.0 g, 53.9 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (37.5 g, 161 mmol) in acetone (250 mL) was stirred at 60 C. for 12 h. On completion, the reaction mixture was filtered and concentrated in vacuo to give a residue. The residue was purified by column chromatography to give the title compound (12.0 g, 74% yield) as a white solid. 1H NMR (400 MHz, CDCl3) delta 7.91-7.84 (m, 2H), 7.77-7.72 (m, 2H), 3.96-3.90 (m, 2H), 384-377 (m, 4H), 3.42 (t, J==6.0 Hz, 21-).

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-(2-bromoethoxy)ethane, its application will become more common.

Reference:
Patent; Kymera Therapeutics, Inc.; Mainolfi, Nello; Ji, Nan; Kluge, Arthur F.; Weiss, Matthew M.; Zhang, Yi; (1443 pag.)US2019/192668; (2019); A1;,
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Application of 2398-37-0,Some common heterocyclic compound, 2398-37-0, name is 1-Bromo-3-methoxybenzene, molecular formula is C7H7BrO, 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.

A round-bottomed flask was charged acetyl chloride (4.20g, 53.56mmol, leq), AICI3 (7.13g, 53.56mmol, leq), and carbon disulfide (80mL). To the mixture was added dropwise a solution of 3-bromoanisole (9.75g, 52.13mmol) in carbon disulfide (20mL) and stirred for 16 h. The resulting solution was diluted with ice water (l OOmL) and extracted with CH2G12 (50mLx3). The extracts were washed with H20, brine, and IN NaOH (30mL). The organic layer was dried over MgS04 and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexanes = 1 :10) to afford the title compound (6.2g, 51%).1H NMR (300MHz, CDC13) delta 7.48(dd, J = 8.4Hz, 1,2Hz, 1H), 7.04(brs. 1H), 6.76(dd, 1H), 3.74(s, 3H), 2.52(s, 3H)

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-3-methoxybenzene, its application will become more common.

Reference:
Patent; KOREA RESEARCH INSTITUTE OF CHEMICAL TECHNOLOGY; HEO, Jung Nyoung; BAE, Myung-Ae; KIM, Nack Jeong; CHANG, Sung Youn; KANG, Namsook; YOO, Sung Eun; HWANG, Eun Sook; WO2011/30955; (2011); A1;,
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Reference of 64115-88-4, 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. 64115-88-4 name is 1-Bromo-2-(trifluoromethoxy)benzene, 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.

Synthesis of (2-amino-5-bromo-pyridin-3-yl)-(2-trifluoromethoxy-phenyl)-methanone To a flame-dried 100 ml round bottomed flask was added 1-bromo-2-(trifluoromethoxy)benzene (2.39 g, 9.9 mmol). The flask was fitted with a rubber septum, purged with nitrogen then charged with anhydrous THF (20 ml). The solution was cooled to -78 C. for 10 min, then a 2.5 M solution of n-butyl lithium in hexanes (3.9 ml, 9.8 mmol) was added dropwise over 3 minutes. The resulting solution was stirred at -78 C. for 40 minutes under nitrogen, then a solution of 739 mg (2.84 mmol) of 2-amino-5-bromo-N-methoxy-N-methyl-nicotinamide in 5 ml of THF was added dropwise over 3 minutes. The resulting red solution was allowed to warm to room temperature over 5 hours, then the reaction was quenched by addition of 10 ml of a saturated aqueous solution of ammonium chloride. Ethyl acetate (50 ml) was added, and the layers were separated. The aqueous fraction was extracted three times with ethyl acetate, and the combined organic fractions were washed with brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes gave 530 mg (52%) of (2-amino-5-bromo-pyridin-3-yl)-(2-trifluoromethoxy-phenyl)-methanone as a yellow-orange solid. 1H-NMR (CDCl3) delta=8.29 (d, 1H), 7.60 (m, 2H,), 7.45 (t, 1H), 7.42 (m, 3H), 1.79(br. s, 2H); MS m/z: 361 [MH]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2-(trifluoromethoxy)benzene, and friends who are interested can also refer to it.

Reference:
Patent; SGX Pharmaceuticals, Inc.; US2006/30583; (2006); A1;,
Ether – Wikipedia,
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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. 1758-46-9, name is 2-Phenoxyethylamine, A new synthetic method of this compound is introduced below., Computed Properties of C8H11NO

General procedure: A solution of 2-phenoxyethylamine (1.31 mL, 10 mmol) in methanol (10 mL) was added to a solution of triethylamine(Et3N) (2.76 mL, 20 mmol) in methanol (10 mL) at 0 C. A solution of 2-chloropyridine (3.80 mL, 40 mmol) in methanol(10 mL) was then added at 0 C under N2. After being stirred for 30 min, the reaction mixture was heated to 25 C and stirred for 3 days. Then, the solvent was evaporated under reduced pressure to afford a yellow solid L1 washed with methanol and dried under vacuum. Yield: 2.31 g (79%).FTIR data (KBr, pellet, cm-1): upsilon 3335, 3057, 2922, 1573,1436, 1243. 1H NMR (400 MHz, CDCl3,ppm): delta 3.94 (t,2H, CH2,J 47.8 Hz), 4.59 (t, 2H, CH2),6.85 (t, 2H, Py-H),6.87 (d, 2H, Py-H, J 7.1 Hz), 7.15 (d, 2H, Ph-H), 7.26 (t,1H, Ph-H), 7.54 (t, 2H, Ph-H), 7.57 (t, 2H, Py-H), 8.33 (d,2H, Py-H). 13C NMR (100 MHz, CDCl3,ppm): delta 42.83,67.63, 115.72, 116.79, 117.17, 121.13, 130.02, 137.32,147.14, 157.30, 159.39. ESI-MS (m/z): 291.16 [L1 + H]+.Anal. Calcd for C18H17N3O(Found) %: C, 74.23 (74.01); H,5.84 (5.71); N, 14.43 (14.13).

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; Wang, Jun; Liu, Jinyi; Chen, Liduo; Lan, Tianyu; Wang, Libo; Transition Metal Chemistry; vol. 44; 7; (2019); p. 681 – 688;,
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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. 22236-10-8, name is 4-(Difluoromethoxy)aniline, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H7F2NO

4-(Difluoromethoxy)aniline (1 g, 6.28 mmol) was dissolved in aqueous hydrochloric acid (12%, 7.35 ml, 25.1 mmol). The solution was cooled to 0 C. and sodium nitrite (434 mg, 6.28 mmol) dissolved in water (2 ml) was slowly added at a temperature below 5 C. After being stirred at 0 C. for 30 min, a solution of ethyl isocyanoacetate (711 mg, 6.28 mmol) and sodium acetate (5.16 g, 62.8 mmol) in MeOH (20 ml) and water (6 ml) was slowly added dropwise at the same temperature. The reaction mixture was stirred for 2 h at 0 C. The solvent was evaporated, 1 M hydrochloric acid was added and the mixture was extracted with ethyl acetate. The organic phase was washed with sodium bicarbonate solution and brine and dried with MgSO4. After chromatography (Silica gel, 40 g, 50% EtOAc in heptane) 220 mg ester was obtained that was dissolved in a mixture of tetrahydrofuran (2 ml), methanol (1 ml) and water (1 ml). Lithium hydroxide hydrate (97.8 mg, 2.33 mmol) was added and the solution was heated to 80 C. for 2 h. The solvent was removed under reduced pressure. The residue obtained was dissolved in 1 M hydrochloric acid and the solution was extracted with ethyl acetate twice. The combined organic layers were dried over MgSO4 and evaporated. The orange solid was recrystallized in a mixture of heptane and ethyl acetate (4:1). 121 mg (7%) of an off-white solid was obtained. 1H NMR (300 MHz, CDCl3) ? ppm: 7.34 (t, 1H; J=73 Hz), 7.41 (d, 2H; J=8.7 Hz), 7.95 (d, 2H; J=8.7 Hz), 9.38 (s, 1H).

According to the analysis of related databases, 22236-10-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hoffmann-La Roche Inc.; Galley, Guido; Ghellamallah, Cedric; Norcross, Roger; Pflieger, Philippe; US2015/191458; (2015); A1;,
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Adding a certain compound to certain chemical reactions, such as: 62415-74-1, name is 1,2-Dibromo-4-methoxybenzene, 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 62415-74-1, Product Details of 62415-74-1

General procedure: Into a dried two-necked flask (50 mL) equipped with a condenser were placed a stirrer bar, Mg powder (99.9%, 8 mmol), LiCl (8 mmol),DMI (10 mL), and chlorotrimethylsilane (16 mmol). After stirring the mixture at rt for 15 min, 1,2-dibromoarene (1 mmol) was added and the mixture was stirred for 4 h. The mixture was quenched with sat.NaHCO3 and the resulting precipitates were filtered off. The filtrate was extracted with hexane (3 ×) and the combined organic extracts were washed with brine, dried (anhyd Na2SO4), and concentrated by a rotary evaporator. The crude product was purified by column chromatography (silica gel, hexane or hexane/CH2Cl2).

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, 1,2-Dibromo-4-methoxybenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Article; Kitamura, Tsugio; Yamada, Rin; Gondo, Keisuke; Eguchi, Nobuo; Oyamada, Juzo; Synthesis; vol. 49; 11; (2017); p. 2495 – 2500;,
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These common heterocyclic compound, 75148-49-1, name is 3-Bromobenzaldehyde Diethyl Acetal, 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. category: ethers-buliding-blocks

In an open ChemGlass vial with pressure -release top, a stirred mixture of 3- bromobenzaldehyde diethylacetal (Aldrich, St. Louis, MO) (65 mg, 0.25 mmol), palladium(II) acetate (5.5 mg, 0.025 mmol), 2-dicyclohexylphosphino-2′,6′- diisopropoxybiphenyl (23 mg, 0.05 mmol), K2C03 (138 mg, 1.0 mmol) and trans-2- (trifluoromethyl)cyclopropylboronic acid MIDA ester (99 mg, 0.38 mmol) in toluene (2.5 mL) and H20 (0.5 mL) was de-gassed with N2 for 15 minutes, then the reaction mixture placed under nitrogen, sealed and heated to 100 C and stirred overnight. After allowing to cool, the reaction mixture was diluted with H20 (15 mL) and EtO Ac (20 mL), filtered through Celite and the filter cake washed with EtO Ac (2 x 20 mL). The filtrate was partitioned and the aqueous layer extracted with EtOAc (2 x 15 mL). The combined organic extracts were dried (Na2S04), filtered and concentrated under vacuum to leave a crude residue. The residue was purified by preparative thin-layer chromatography (3 prep TLC plates used) using EtOAc / hexane (1:4) as eluent to give the product (58.6 mg, 69% – yield adjusted for purity) as an oil [note: desired product contaminated with another compound after prep TLC – approximately 85% pure by 1H NMR and LC/MS].[00221] 1H NMR (CDC13, 300MHz): delta 7.34-7.24 (m, 3H), 7.08 (dt, / = 7.1, 1.7 Hz, 1H), 5.46 (s, 1H), 3.67-3.48 (m, 4H), 2.40-2.34 (m, 1H), 1.88-1.75 (m, 1H), 1.40-1.31 (m, 1H), 1.24 (t, 7 = 7.1 Hz, 6H), 1.20-1.14 (m, 1H). 19F NMR (CDC13, 282 MHz): -66.8 (d, / = 6.8 Hz), m/z = no mass-ion by LC/MS or HRMS.

The synthetic route of 3-Bromobenzaldehyde Diethyl Acetal has been constantly updated, and we look forward to future research findings.

Reference:
Patent; RIGEL PHARMACEUTICALS, INC.; DUNCTON, Matthew; SINGH, Rajinder; WO2012/75316; (2012); A2;,
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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. 588-63-6, name is (3-Bromopropoxy)benzene, This compound has unique chemical properties. The synthetic route is as follows., Computed Properties of C9H11BrO

To a flame-dried Schlenk tube containing CpFe(CO)2Cl (6) (10.3 mg, 0.05 mmol),3-bromopropyl phenyl ether (1j) (223 mg, 1.04 mmol), THF (0.25 mL), n-BuMgCl (2a)(2M in THF, 0.75 mL, 1.5 mmol), and 1,3-butadiene (90 mL as gas, 4.0 mmol) wereadded successively at ?78 C followed by stirring at 0 °C for 2 h and rt for 22 h. Thereaction was quenched by the addition of sat NH4Cl aq., extracted with Et2O (10 mL x3), concentrated, and purified by PTLC (eluent: hexane/Et2O = 99/1) to obtain heptylphenyl etherS2 (3ja) as yellow oil (79.5 mg, 40percent).

According to the analysis of related databases, 588-63-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Iwasaki, Takanori; Shimizu, Ryohei; Imanishi, Reiko; Kuniyasu, Hitoshi; Kambe, Nobuaki; Chemistry Letters; vol. 47; 6; (2018); p. 763 – 766;,
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