Month: November 2020

327-52-6, A common compound: 327-52-6, name is 1-Bromo-2,4,5-trifluorobenzene, belongs to bromides-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.

[0122] Into a 100 mL three- necked flask were added 4.62 g 1- bromo- 2, 4, 5- trifluorobenzene (0.022 mol) andanhydrous tetrahydrofuran (50 mL) . The resulting mixture was cooled to- 20 C. The solution of isopropylmagnesiumbromide (22 mmol) in tetrahydrofuran (22 ml, 1 M THF) was slowly added dropwise under nitrogen. After the additionwas complete, the reactants were maintained at- 20 C for later use.[0123] Cuprous bromide – dimethyl sulfide (0.41 g, 0.002 mol) was suspended in 5 ml anhydrous tetrahydrofuran. Theresulting mixture was cooled to -5 C. The Grignard reagent as described above was slowly added dropwise undernitrogen. After 15 min, a solution of the acridine compound as shown in the above reaction formula (4.16 g, 0.015 mol)in 30 mL tetrahydrofuran was slowly added dropwise. After additional 5 min, 50 mL saturated solution of ammoniachloride was added to quench the reaction. Into this obtained solution was added 50 mL ethyl acetate. The separatedwater layer was extracted with another 50 mL ethyl acetate. The obtained organic layers were collected together andfurther was washed with saturated solution of sodium chloride and then dried over anhydrous sodium sulfate, followedby filtration and concentration to obtain a crude product, which was further treated by column chromatography to obtaina compound (4.98 g, 0.0128 mol, yield 85%).1H NMR (400 MHz, CDCl3) delta 7.87?7.61 (m, 5H), 7.15?6.94 (m, 1H), 6.88 (d, J = 6.8 Hz, 1 H), 5.02 (d, J = 8.9 Hz, 1 H),4.00 – 3.80 (m, 1 H), 2.92?2.76 (m, 1 H), 2.76?2.64 (m, 1H), 2.64? 2.44 (m, 2H), 2.06 (d, J = 14.6 Hz, 3H), 1.84 (s, 1H), 1.62 (s, 1H). Ms (M++1): 390.

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-Bromo-2,4,5-trifluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Zhejiang Hisoar Pharmaceutical Co., Ltd; PAN, Xianhua; LI, Weijin; ZHANG, Qunhui; RUAN, Libo; YU, Wansheng; DENG, Fei; MA, Tianhua; HUANG, Mingwang; HE, Minhuan; EP2647624; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 7617-93-8, name is 2-Bromo-1,4-bis(trifluoromethyl)benzene, molecular formula is C8H3BrF6, 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. 7617-93-8

All experiments were performed in a previously-described quadrupole ion trap mass spectrometer (modified ThermoFinnigan LCQ DECA) equipped with electrospray ionization (ESI) [15, 17]. In a typical experiment, the dianion precursor was dissolved in methanol (10-4 M) and injected through the electrospray interface at flow rates ranging from 3 to 5 muL/min. The neutral reagents were mixed into the buffer gas by injecting a constant flow of reagent (20-400 muL/h) into a measured flow of helium (1000-1500 mL/min). Reactions were monitored as a function of time at various flow rates (pressures) of the reagent and branching ratios were determined. Time delays and reagent flows were adjusted to obtain plots that covered two to three half-lives of the reactant ion. Reported rate constants were measured at three different reagent flow rates and at least nine kinetic runs were collected on 2 or more days (>18 runs). In the past, we have shown that the ion trap gives reactivity at near ambient temperature [18]. All the arene reagents were obtained from commercial sources.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 7617-93-8, its application will become more common.

Reference:
Article; Eanes, Allison D.; Noin, Diogo O.; Kebede, Maheteme K.; Gronert, Scott; Journal of the American Society for Mass Spectrometry; vol. 25; 1; (2014); p. 10 – 17;,
Bromide – Wikipedia,
bromide – Wiktionary

40161-54-4, 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. 40161-54-4, name is 1-Bromo-2-fluoro-4-(trifluoromethyl)benzene, This compound has unique chemical properties. The synthetic route is as follows.

Example 14; ralphac-(35r,4i?)-7V-cyclopropyl-4- [2-fluoro-4-(trifluoromethyl)phenyl] -4-hydroxy-iV- [3 -(2- methoxyethoxy)-5 -(3 -methoxypropyl)benzyl]piperidine-3 -carboxamide; Step 1: rac-tert-butv (3?4i?V3-alphacvclopropyir3-q-methoxyethoxy)-5-(3- methoxypropyDbenzyll amino } carbonyl)-4- [2-fluoro-4-(trifluoromethyl)phenyl] -4- hydroxypiperidine- 1 -carboxylate; ?-BuLi (2.50 M in THF, 3.11 eq.) was added to a stirred solution of l-bromo-2- fluoro-4-(trifluoromethyl)benzene (3.24 eq.) in THF (1.6 M) at -78 C. The mixture was stirred at -78 0C for 15 min then MgBr2-Et2O (0.4 M in THF, 3.32 eq.) was added dropwise. The mixture was stirred -78 C for 30 min. The resulting solution was cannulated into a solution of keto amide 3.1 (1 eq.) in THF (0.15 M) at -78 C. The reaction mixture was stirred at -78 C for 1 hr then allow to warm slowly to rt with stirring over 12 h. The mixture was quenched with saturated NH4Cl, diluted with Et2O. The organic extract was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (10-75% EtOAc in hexanes) to give the title compound as an oil.

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; MERCK FROSST CANADA LTD.; WO2009/70869; (2009); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 24358-62-1, name is 1-(4-Bromophenyl)ethylamine, molecular formula is C8H10BrN, 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. 24358-62-1

7-Fluoro-lH-benzo[d][l,3]oxazine-2,4-dione (0.500 g; 2.76 mmol), l-(4- bromophenyl)ethanamine (0.474 ml; 3.31 mmol), urea (0.249 g; 4.14 mmol), and 3 ml of DMA were charged in a microwave tube and heated for 10 min at 250 C. The reaction mixture was cooled to rt, mixed with water, and extracted twice with EtOAc. Combined organic phases were dried over Na2S04 and evaporated to dryness. The crude product was purified with CombiFlash (normal phase silica) to yield 389 mg of 3-(l-(4- bromophenyl)ethyl)-7-fluoroquinazoline-2,4(lH,3H)-dione. 1H-NMR (400 MHz, d6- DMSO): delta 1.77 (d, 3H), 6.11 (q, 1H), 6.22 (d, 1H), 6.60 (dd, 1Eta),7.19-7.26 (m, 2H), 7.45- 7.50 (m, 2H), 7.66 (d, 1H), 10.96 (br s, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 24358-62-1, its application will become more common.

Reference:
Patent; ORION CORPORATION; PRUSIS, Peteris; HOeGLUND, Lisa; TOeRMAKANGAS, Olli; HIETANEN, Ari; ARVELA, Riina; VESALAINEN, Anniina; HEIKKINEN, Terhi; WO2015/169999; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

142808-15-9, Name is 4-Bromo-2-fluorobenzotrifluoride, 142808-15-9, belongs to bromides-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.

a) 6-[3-Fluoro-4-(trifluoromethyl)phenyl]-8-nitro-3,4-dihydro-2(1 H)-quinolinoneTo a stirred solution of 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (1.0 g, 4.1 mmol), bis(pinacolato)diboron (1.1 g, 4.3 mmol) and potassium acetate (1.2 g, 122 mmol) in dimethylformamide (50 mL) was added [1 ,1′- bis(diphenylphosphino)ferrocene]dichloropalladium (II) dichloromethane adduct (81 mg, 0.11 mmol). After purging with nitrogen, the reaction was heated to 80 0C and EPO stirred for 2 h. 6-bromo-8-nitro-3,4-dihydro-2(1 H)-quinolinone (example 77a, 1.0 g, 3.7 mmol), cesium fluoride (1.3 g, 8.4 mmol), and tetrakis(triphenylphosphine)palladium (0) (130 mg, 0.11 mmol) were added and the reaction stirred at 100 0C for 18 h. After cooling to room temperature, the reaction was evaporated to dryness under vacuum. The residue was taken up in ethyl acetate, filtered to remove insolubles, washed with 1 M aq hydrochloric acid, brine, dried (MgSO4), filtered and concentrated under vacuum. Purification by flash chromatography on silica gel (3% ethyl acetate/dichloromethane) gave the title compound (0.77 g, 59%) as a yellow solid. MS (ES) m/e 355.0 (M + H)+.; +/- 6-f3-Fluoro-4-(trifluoromethvnphenyl1-3-hyclroxy-3.4-dihvdro-2(1 H)-quinolinone 4-Bromo-2-fluoro-1-(trifluoromethyl)benzene (0.091 mL, 0.375 mmol), bis(pinacolato)diboror) (0.10 g, 0.394 mmol), potassium acetate (0.11 g, 1.12 mmol), dichloro[1 ,1 ‘-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.020 g, 0.027 mmol) in DMF (2.0 mL) were heated to 800C under nitrogen for 2.5 hours. After the reaction was cooled, dichloro[1 ,1’- bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.020 g, 0.027 mmol) was added followed by addition of + 6-bromo-3-hydroxy-3,4-dihydro- 2(1 H)-quinolinone (example 85b, 0.095 g, 0.392 mmol) and 2M Na2CO3 in water (0.98 mL). The reaction was heated to 800C. After 12 hours the reaction mixture was cooled and diluted with ethyl acetate, then washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude reaction mixture was purified using reverse-phase preparative HPLC (10% CH3CN/H2O to 100% CH3CN/H2O with 0.1% TFA) to give the title compound as a solid. 1H NMR (400MHz, D6-DMSO) delta 10.34 (bs, 1 H), 7.79 (m, 2H), 7.69 (m, 2H), 7.59 (d, J = 8.6Hz, 1 H), 6.96 (d, J = 8.3 Hz, 1 H), 5.58 (bs, 1 H), 4.18 (m, 1 H), 3.13 (dd, 1 H), 2.93 (dd, 1 H).

Statistics shows that 4-Bromo-2-fluorobenzotrifluoride is playing an increasingly important role. we look forward to future research findings about 142808-15-9.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2006/113432; (2006); A2;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 615-36-1, name is 2-Bromoaniline, molecular formula is C6H6BrN, 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. 615-36-1

General procedure: Compound 2b-l were synthesized according to the reported method:1A mixture of aniline (10 mmol), iodoalkane (22 mmol) and K2CO3(22mmol) in DMF (80 mL) was refluxed at 75 C. After completion of thereaction monitored by TLC, the mixture was poured into aqueous NaHCO3solution and extracted with ethyl acetate. The organic layer was washed with brine,dried over sodium sulfate and concentrated in vacuo. Purification by columnchromatography on silica gel produced N,N-dimethylanilines 2b-l.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 615-36-1, its application will become more common.

Reference:
Article; Shen, Hang; Zhang, Xiaohui; Liu, Qing; Pan, Jing; Hu, Wen; Xiong, Yan; Zhu, Xiangming; Tetrahedron Letters; vol. 56; 41; (2015); p. 5628 – 5631;,
Bromide – Wikipedia,
bromide – Wiktionary

586-61-8, 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 586-61-8 as follows.

5-cyano-2-fluorobenzeneboronic acid pinacol ester (1.98 g, 8.0 mmol) and 4-bromoisopropylbenzene (2.39 g, 12 mmol) were dissolved in 20 ml of dioxane, and Pd(PPh3)4 was added. (924 mg, 0.8 mmol) and CsCO3 (5.2 g, 16.0 mmol) were reacted at 90 C overnight under nitrogen. The reaction liquid was filtered through diatomaceous earth.The filtrate was spin-dried and then subjected to petroleum ether column chromatography to yield 1.35 g of colorless oily liquid, yield: 70.6%.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 586-61-8, and friends who are interested can also refer to it.

Reference:
Patent; China Pharmaceutical University; You Qidong; Xu Xiaoli; Jiang Fen; Guo Anping; Xu Jiachen; (26 pag.)CN108147978; (2018); A;,
Bromide – Wikipedia,
bromide – Wiktionary

A common heterocyclic compound, 203302-95-8, name is 4-Bromo-3,5-difluoroaniline, molecular formula is C6H4BrF2N, 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. 203302-95-8.

A mixture of 4-bromo-3,5-difluoro-phenylamine (6.0 g, 28.8 mmol), ferrous sulfate (1.82 g), glycerol (8.6 mL), nitrobenzene (1.79 mL) and 5.0 ml of concentrated sulfuric acid (5 mL) was heated gently. After the first vigorous reaction, the mixture was heated to reflux for five hours. Nitrobenzene was removed by distillation in vacuo. The aqueous solution was acidified with glacial acetic acid, and dark brown precipitate separated, which was purified by flash chromatography (silica gel, petroleum:ethyl acetate= 12:1) to return title compound as a white solid (3.5 g, 49.8%).

The synthetic route of 4-Bromo-3,5-difluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SGX PHARMACEUTICALS, INC.; WO2008/144767; (2008); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 583-70-0, name is 2,4-Dimethylbromobenzene, belongs to bromides-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 583-70-0, 583-70-0

to a suspension of magnesium powder (239 mg, 9.79 mmol) in dry THF (small amount) was added dropwise 1 -bromo-2,4-dimethylbenzene (1.64 g, 8.86 mmol) diluted in dry THF (20 mL) and the reaction was heated at 40C. After completion of Grignard reagent, 2-methyl-N-[(5-methylfuran-2- yl)methylidene]propane-2-sulfinamide Ex.19a (995 mg, 4.66 mmol) diluted in THF (10 mL) was added to the solution. The reaction mixture was stirred at rt overnight. Water was added to quench the reaction. The two layers were partitionated and the organic layer was dried over Mg504, filtered and the solution was concentrated under reduced pressure. The crude material was purified by silica gel column chromatography using a gradient of hexanes/EtOAc ([5:11 to [4:1]) to afford N-[(2,4-di methyl phenyl)(5-methylfuran-2-yl)methyl]-2- methylpropane-2-sulfinamide (1 .27 g, 85%) as yellowish oil

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, 2,4-Dimethylbromobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GENFIT; DELHOMEL, Jean-Francois; PERSPICACE, Enrico; MAJD, Zouher; PARROCHE, Peggy; WALCZAK, Robert; (284 pag.)WO2018/138362; (2018); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

A common heterocyclic compound, 10016-52-1, name is 2,8-Dibromodibenzo[b,d]furan, molecular formula is C12H6Br2O, 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. 10016-52-1.

To a 1 L reaction flask was added toluene solvent (450 ml), 2,8-dibromodibenzofuran (11.74 g, 36 mmol),Intermediate I-21 (36.22 g, 90 mmol), Pd2 (dba) 3 (990 mg, 1.08 mmol),BINAP (1.65 g, 16.5 mmol) and sodium tert-butoxide (9.9 g, 100.8 mmol),Dissolved by stirring, and refluxed under nitrogen for 24 hours.After completion of the reaction, the reaction solution was washed with dichloromethane and distilled water and then evaporated.The organic layer was dried over anhydrous magnesium sulfate. After filtered, solvent was removed, and purified by column chromatography using cyclohexane: ethyl acetate = 10:1 as eluent.Finally, solid compound 21 (25.81 g, yield 74%) was obtained, and the solid purity was 99.6% by HPLC.

The synthetic route of 2,8-Dibromodibenzo[b,d]furan has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Changchun Hai Purunsi Technology Co., Ltd.; Zhao Qian; Liu Hui; Han Chunxue; (55 pag.)CN110407829; (2019); A;,
Bromide – Wikipedia,
bromide – Wiktionary