Month: November 2020

A common heterocyclic compound, 444-14-4, name is 2-Bromo-4,6-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. 444-14-4.

3. Amination The 1-bromo-3,5-difluorobenzene generated by diazotization of 2-bromo-4,6-difluoroaniline can be converted to 100 lbs. of 3,5-difluoroaniline as follows: A suitable pressure reactor designed for a minimum of 300 psig pressure is charged with 288.1 lbs. of 29% aqueous ammonia. The reactor is designed to provide for pressure control via temperature control of the reaction. To the ammonia charge, 4.7 lbs. of cuprous oxide is added, and the 168.2 lbs. of crude 1-bromo-3,5-difluorobenzene product is added. The reaction mixture is heated to about 135 C. using temperature control to maintain a maximum pressure of 300 psig, and the reaction pressure is maintained at about 300 psig by slowly increasing the reaction temperature to 165 C. over 4.5 hours. The reaction mixture is held at 165 C. for one additional hour, and then a sample is assayed for completeness of the reaction. If more than 0.5% by weight of 1-bromo-3,5-difluorobenzene remains unreacted, then the reaction mixture is held at 165 C. for one more hour and re-assayed. This process is repeated until less than 0.5% by weight of unreacted 1-bromo-3,5-difluorobenzene remains.

The synthetic route of 2-Bromo-4,6-difluoroaniline has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BASF Corporation; US5977412; (1999); A;,
Bromide – Wikipedia,
bromide – Wiktionary

3814-30-0, 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. 3814-30-0, name is (Bromomethyl)cyclopentane, A new synthetic method of this compound is introduced below.

Preparation 78: 6-Bromo-1 -(cyclopentylmethyl)-2-(1 -methyl-1 H-pyrazol-4-yl)-1 H- pyrrolo[3,2-c]pyridine; [00248] Sodium hydride (60% in mineral oil, 10.8mg, 0.271 mmol) was added to a solution of 6-bromo-2-(1 -methyl-1 H-pyrazol-4-yl)-1 H-pyrrolo[3,2-c]pyridine (Preparation 22, 50mg, 0.180mmol) in DMF (780ml_). The reaction mixture was then stirred for 15 minutes at room temperature before the addition of (bromomethyl)cyclopentane (44mg, 0.271 mmol). The reaction mixture was then stirred overnight at room temperature and for 24 hours at 60C. Sodium hydride (60% in mineral oil, 5mg, 0.125mmol) was added and the reaction was stirred for another 7 hours at 60C. The reaction mixture was then diluted with water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2S04), filtered and concentrated under reduced pressure. The crude was purified via Biotage silica gel column chromatography eluting with (DCM/EtOAc 99/1 to 80/20) to afford the title product as a colourless oil (45mg, 69%). 1 H NMR (500 MHz, CDCI3) d 1 .10-1 .19 (m, 2H), 1 .46-1 .64 (m, 6H), 2.24-2.33 (m, 1 H), 4.03 (s, 3H), 4.09 (d, J = 7.6Hz, 2H), 6.53 (d, J = 0.9Hz, 1 H), 7.45 (t, J = 0.9Hz, 1 H), 7.59 (s, 1 H), 7.68 (s, 1 H), 8.60 (d, J = 0.9Hz, 1 H). LC (Method B)-MS (ESI, m/z) fR 3.03 min, 359 [(M+H+), 100%].

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; CANCER RESEARCH TECHNOLOGY LIMITED; BAVETSIAS, Vassilios; ATRASH, Butrus; NAUD, Sebastien Gaston Andre; SHELDRAKE, Peter William; BLAGG, Julian; WO2012/123745; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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 38573-88-5 as follows. 38573-88-5

Intermediate 25; 4-(2,3-Difluorophenyl)-3-butyn-1-ol; To a solution of 1-bromo-2,3-difluorobenzene (10.0 g, 51.82 mmol, Aldrich) in dimethylamine (200 ml) under nitrogen were added Bis(tripheylphenylphosphine)palladium(II) dichloride (0.73 g, 1.037 mmol), copper(I) iodide (0.1 g, 0.525 mmol) and 3-butyn-1-ol (11.76 ml). The temperature was raised from ambient to 65¡ã C. and held there with stirring for 20 h, after which the mixture was cooled and all volatiles removed by rotary evaporation. The residue was partitioned between a mixture of 2N HCl (400 ml), brine (100 ml) and dichloromethane (400 ml). A second 100 ml dichloromethane extract and the layers were separated and aqueous was washed with DCM (100 ml). Extracts were combined and the mixture passed through a hydrophobic frit and evaporated under reduced pressure to give a dark brown oil. This oil was purified using a CombiFlash.(R). Companion.(R). 330 g Redisep.(R). silica column eluting with a gradient of cyclohexane:ether (0 to 100percent) affording the title compound as a light orange oil (9.149).H.p.l.c. Rt=2.76 min.1H nmr (CDCl3) delta: 1.88 (1H, t), 2.75 (2H, t), 3.86 (2H, q), 7.01 (1H, m), 7.10 (1H, m), 7.17 (1H, m).

According to the analysis of related databases, 38573-88-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Camus, Laure; Chudasama, Reshma; Day, Caroline Jane; Deshmukh, Deepali; Gleason, John Gerald; Harling, John David; Lee, Chao-Pin; Saklatvala, Paula; Senger, Stefan; Vallance, Sarah; Watson, John; Watson, Nigel Stephen; Young, Robert John; Yuan, Barbara; US2008/306045; (2008); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 4263-52-9, name is Sodium 2-bromoethanesulphonate, molecular formula is C2H4BrNaO3S, 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. 4263-52-9

10.5 g sodium 2-bromoethanesulfonate was added to a solution of 110 ml benzyl alcohol and 1.15 g sodium benzyloxide.Then the mixture was boiled under reflux four times. The mixture was then concentrated under vacuum to dryness and then boiled with ethyl alcohol three times. The alcohol was filtered and concentrated to dryness.The yield was 9.8 g and was confirmed by UV and IR.Pure crystals were obtained by boiling the resultant sodium 2-benzylether ethanesulfonate in ethyl alcohol, filtering, then cooling the solution to crystallize pure sodium 2-benzylether ethanesulfonate crystals out of solution.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 4263-52-9, its application will become more common.

Reference:
Patent; GEISTLICH PHARMA AG; PFIRRMANN, Rolf W.; (101 pag.)WO2016/98054; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

16518-62-0, 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. 16518-62-0, name is 3-Bromo-N,N-dimethylaniline, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: Boronic acid, aryl halide, Pd(dppf)Cl2*DCM, CsF, and dry dimethoxyethane (DME) were introduced in a 100 mL shlenk tube. The reaction mixture was flushed three times by vacuum/argon andstirred at 80 ¡ãC overnight. The reaction mixture was filtered through celite and rinsed with EtOAc. The solvent was removed under vacuum and the residue was purified by flash column chromatography (EtOAc-hexane).

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:
Article; Roy, Pierre-Philippe; D’Souza, Kenneth; Cuperlovic-Culf, Miroslava; Kienesberger, Petra C.; Touaibia, Mohamed; European Journal of Medicinal Chemistry; vol. 118; (2016); p. 290 – 298;,
Bromide – Wikipedia,
bromide – Wiktionary

452-92-6, 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 452-92-6 as follows.

5-bromo-2,4-difluoroaniline (500 mg, 2.40 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)benzoate (BSfTERMEDIATE 16, 797 mg, 2.88 mmol), sodium carbonate (2.40 mL, aq., 2M, 2.88 mrnol), l,l’-bis(diphenylphosphino) ferrocene-palladium dichloride dichloromethane adduct (196 mg, 0.24 mmol) and ethanol (15 ml) were heated in an 80 0C oil bath for 3 hours then allowed to cool to ambient overnight. Volatiles were removed under reduced pressure. The pot residue was worked up w/DCM /brine/Na2Sthetayfltratio:n/concentration to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge). The column was eluted by a 0% to 40% EtOAc/hexa?es gradient mixture. Related fractions were pooled and concentrated in vacuo to afford the title compound. LCMS (ESI) calc. = 277.09; found = 278.03 (M+l)+.; Step A methyl 5′-amino-2′,4′-difluoro-2-methylbiphenyl-4-carboxyIate5-bromo-2,4-difluoroaniline (500 mg, 2.40 mmol), methyl 3-methyl-4-(4,4,5,5-tetrarnethyl-l,3,2- dioxaborolan-2-yl)benzoate (INTERMEDIATE 16, 797 mg, 2.88 mmol), sodium carbonate (2.40 mL, aq., 2M, 2.88 mmol), l,r-bis(diphenylphosphino) ferrocene-palladium dichloride dichloromethane adduct (196 mg, 0.24 mmol) and ethanol (15 ml) were heated in an 80 0C oil bath for 3 hours then allowed to cool to ambient overnight. Volatiles were removed under reduced pressure. The pot residue was worked up w/DCM /brine/Na2SCVfltration/concentration to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge). The column was eluted by a 0% to 40% EtOAc/hexanes gradient mixture. Related fractions were pooled and concentrated in vacuo to afford the title compound. LCMS (ESI) calc. = 277.09; found = 278.03 (M+l)+.

According to the analysis of related databases, 5-Bromo-2,4-difluoroaniline, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK & CO., INC.; WO2007/79186; (2007); A2;,
Bromide – Wikipedia,
bromide – Wiktionary

51437-00-4, Adding some certain compound to certain chemical reactions, such as: 51437-00-4, name is 4-Bromo-1-fluoro-2-methylbenzene, 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 51437-00-4.

Example 10A Methyl N-(4-fluoro-3-methylphenyl)piperidine-4-carboxylate starting with 10.6 g (74.0 mmol) of methyl piperidine-4-carboxylate and 4.67 g (24.7 mmol) of 5-bromo-2-fluorotoluene, the general procedure [E] gives 2.74 g (40% of theory) of product. HPLC (method 1): Rt=3.48 min Examples 11A to 17A from the table below can be prepared in accordance with the general procedure [E]. General Procedure [F]: Hydrolysis of the N-arylpiperidine-4-carboxylic Esters 1.0 equivalent of the N-arylpiperidine-4-carboxylic ester is dissolved in dioxane, and 2.0 equivalents of 1N aqueous sodium hydroxide solution are added. The mixture is stirred at 80 C. for 16 hours, and after the reaction has ended (the reaction is monitored by analytical HPLC) the mixture is concentrated. The residue is then taken up in water and adjusted to pH=5 using 1N hydrochloric acid. The resulting precipitate is filtered off, washed with a little water and cyclohexane and dried at room temperature under high vacuum. If the purity of the product is not high enough, the product is purified by preparative HPLC on an RP phase.

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 51437-00-4.

Reference:
Patent; Bayer HealthCare AG; US2007/281953; (2007); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

608-30-0, 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. 608-30-0, name is 2,6-Dibromoaniline, A new synthetic method of this compound is introduced below.

4-tert-Butylphenylboronic acid (4.81 g, 27.0 mmol) dissolved in ethanol (18 mL) and 2 M Na2CO3 (36 mL, 72 mmol) were added to a solution of 2,6-dibromoaniline (2.258 g, 9.0 mmol) in toluene (90 mL). To this solution, Pd(PPh3)4 (1.26 g, 1.0 mmol) was added. The mixture was heated to reflux for 72 h. After cooling to room temperature, the mixture was filtered and an excess of aqueous HCl was slowly added to the filtrate until no more white solid precipitated. The residue was suspended in diethyl ether after filtration and then an excess of 2 M Na2CO3 was slowly added until the solid was totally dissolved. The organic layer was dried over Na2SO4 and then the solvent was evaporated to give white solid (1.80 g, yield 56%). 1H NMR (500 MHz, CDCl3, delta in ppm): 7.47-7.52 (m, 8H, Ar-Hm), 7.15 (d, 2H, Ar-Ho), 6.89 (t, 1H, Ar-Hp), 3.95 (s,2H, NH2), 1.40 (s, 18H, CH3).

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; Pan, Huijie; Zhu, Liang; Li, Jiewei; Zang, Dandan; Fu, Zhisheng; Fan, Zhiqiang; Journal of Molecular Catalysis A: Chemical; vol. 390; (2014); p. 76 – 82;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 327-52-6

EXAMPLE H 3-Bromo-2,5,6-trifluorobenzaldehyde To a solution of 1-bromo-2,4,5-trifluoro benzene (25 g, 0.12 mol) in THF (200 mL) at -78 C. was added LDA (80 mL, 1.5 M) dropwise. The mixture was stirred at -78 C. for 1 hour, then N-formylpiperidine (16 g, 0.144 mol) was added in one portion and stirring continued for 2 hours. An additional 15 g of N-formylpiperidine was then added every 0.5 hour in 5 g portions. The reaction was quenched with 3N HCl (pH 3) at -78 C. The reaction was warmed to 0 C. and partitioned between H2 O and ether. The ether layer was dried and concentrated and the residue was distilled to provide 13 g (45%) of the desired aldehyde; bp 63-65 C. (0.2 mm).

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, 327-52-6, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Warner-Lambert Company; US5047538; (1991); A;,
Bromide – Wikipedia,
bromide – Wiktionary

38573-88-5, 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. 38573-88-5, name is 1-Bromo-2,3-difluorobenzene belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

Example 2Preparation of (4-bromo-2,3-difluorophenyl)trimethylsilaneDiisopropylamine (7.86 grams (g), 78 mmol) was dissolved in tetrahydrofuran (THF; 104 mL) and cooled to -75¡ã C. utilizing a dry ice/acetone bath.A solution of n-BuLi (2.5 M in hexanes; 22.80 mL, 57.0 mmol) was added dropwise, and the solution was again cooled to -75¡ã C. 1-Bromo-2,3-difluorobenzene (10 g, 51.8 mmol) was dissolved in THF (25.9 mL), and the solution was added dropwise keeping the temperature below -60¡ã C.The reaction mixture was then allowed to warm to -15¡ã C. before cooling again to -75¡ã C. TMSCl (7.29 mL, 57.0 mmol) was then added dropwise, and the reaction mixture was allowed to warm to 25¡ã C. and then concentrated under vacuum.The residue was partitioned between ethyl acetate (EtOAc) and H2O.The organic phase was washed twice more with H2O and concentrated.Kugelrohr distillation at 88¡ã C. provided the product in greater purity but an impurity was distilling at that temperature.Kugelrohr distillation of that purified distillate at 75¡ã C. led to purer product but some product was left in the pot.This process yielded the title compound as a clear oil (3.0 g, 21.83percent, 90percent purity): 1H NMR (300 MHz, CDCl3) delta 7.28 (ddd, J=7.8, 5.2, 1.3 Hz, 1H), 6.98 (ddd, J=8.0, 4.8, 1.9 Hz, 1H), 0.32 (s, 9H); EIMS m/z 264, 266.

The synthetic route of 38573-88-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Epp, Jeffrey B.; Lowe, Christian T.; Renga, James M.; Schmitzer, Paul R.; Eckelbarger, Joseph D.; Guenthenspberger, Katherine A.; Siddall, Thomas L.; Yerkes, Carla N.; Fischer, Lindsey G.; Giampietro, Natalie C.; Kister, Jeremy; Roth, Joshua; US2013/5574; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary