Month: July 2021

Electric Literature of 108649-59-8, 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. 108649-59-8 name is 1-(2-Bromoethyl)-2,4-dichlorobenzene, 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.

General procedure: Magnesium turnings (13.2 g, 0.55 mol) were placed in dry THF (25 mL) undernitrogen. A small amount (10 mL) of (2-bromoethyl)benzene (92.5 g, 0.50 mol) dissolvedin dry THF (300 mL), added to the magnesium slurry and stirred for a few minutes withwarming until the reaction commenced. The remainder of the (2-bromoethyl)benzenesolution was added dropwise to maintain reflux over an hour, then the reaction mixturewas aged at reflux for an additional an hour. The reaction mixture was cooled to 25 C. In a separate flask, diethyl oxalate (88.2 g, 0.6 mol) was dissolved in dry THF (100mL) and cooled to -10 C. The supernatant solution of (2-phenylethyl)magnesiumbromide was sucked under nitrogen through a sintered-glass filter into a dropping funnel.The reaction temperature was held at -10 C as the solution of Grignard reagent wasadded dropwise over an hour to the diethyl oxalate. The sintered-glass funnel anddropping funnel were then rinsed with dry THF (100 mL), and the rinse was added to thebatch. The reaction mixture was allowed to stand for 30 min and then quenched byaddition of 3 M HCl (145 mL).Hexane (500 mL) was added, and the aqueous layer was discarded. The organicphase was washed with brine (100 mL) and saturated NaHCO3 (100 mL), until theaqueous layer measured to pH 5.0. The organic phase was dried with anhydrous Na2SO4.Filtered and washed with hexane, and the combined layers were concentrated to an oil invacuum. The crude keto ester (103.0 g) was vacuum distilled at 105-110 C (0.2-0.3 mmHg) to afford a colourless oil 90.0 g with 60% yield.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-(2-Bromoethyl)-2,4-dichlorobenzene, and friends who are interested can also refer to it.

Reference:
Article; Zhu, Lufeng; Chen, Houhe; Meng, Qinghua; Fan, Weizheng; Xie, Xiaomin; Zhang, Zhaoguo; Tetrahedron; vol. 67; 34; (2011); p. 6186 – 6190;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 468075-00-5,Some common heterocyclic compound, 468075-00-5, name is 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, molecular formula is C7H3BrClF3O, 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 mixture of 2-bromo-l-chloro-4-(trifluoromethoxy)benzene (5.00 g, 18.15 mmol), Pd(dppf)Cl2.CH2Cl2 (1.48 g, 1.82 mmol) and Et3N (5.51 g, 54.45 mmol) in EtOH (30 mL) was degassed, and refilled with CO. The reaction was stirred under CO (50 psi) for 16 hours at 80 C, at which point the desired product was observed by LCMS. The reaction mixture was diluted with EtOH (20 mL), and filtered through a Celite pad. The filtrate was concentrated. The residue was purified by flash chromatography on silica gel (EtOAc in PE = 0% 5%) to afford compound 12-b (2.40 g, 8.93 mmol) as an oil. 1H NMR (400MHz, CDC13) deltaH = 7.66 – 7.59 (m, 1H), 7.42 (d, 1H), 7.24 – 7.19 (m, 1H), 4.36 (q, 2H), 1.35 (t, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, its application will become more common.

Reference:
Patent; PRAXIS PRECISION MEDICINES , INC.; REDDY, Kiran; MARTINEZ BOTELLA, Gabriel; GRIFFIN, Andrew, Mark; MARRON, Brian, Edward; (244 pag.)WO2018/148745; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 13918-92-8, A common heterocyclic compound, 13918-92-8, name is 2,4-Difluorobenzene-1-sulfonyl chloride, molecular formula is C6H3ClF2O2S, 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.

Reference Example 143; tert-butyl ({5- (2-cyanopyridin-3-yl) -l-[ (2,4- difluorophenyl) sulfonyl] -lH-pyrrol-3-yl}methyl)methylcarbamate; To a suspension of sodium hydride (60% in oil, 26.0 mg) in tetrahydrofuran (3 mL) was added tert-butyl {[5- (2- cyanopyridin-3-yl) -lH-pyrrol-3-yl]methyl Jmethylcarbamate (156 mg) at room temperature, and the mixture was stirred for 15 min. After stirring, 15-crown-5 (143 mg) and 2,4- difluorobenzenesulfonyl chloride (159 mg) were added dropwise and the mixture was further stirred at room temperature for 1 hr. Saturated aqueous ammonium chloride solution was added, and the mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9: 1-*2: 1) to give the title compound as a colorless oil (yield 208 mg, 85%).1H-NMR (CDCl3) delta: 1.48(9H,s), 2.85 (3H,brs) , 4.29 (2H,brs) , 6.46(lH,brs) , 6.80-6.88 (IH,m) , 6.93 (lH,ddd, J=IO.2, 8.1, 2.4Hz) , 7.20(lH,ddd, J=8.8, 8.0, 5.8Hz) , 7.46 (IH, s) , 7.55(lH,dd, J=7.9,4.7Hz) , 7.93 (IH, dd, J=8.0, 1.6Hz) , 8.69(lH,dd, J=4.7,1.7Hz) .

The synthetic route of 13918-92-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; WO2008/108380; (2008); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 7006-52-2, name is N-Methyl-3-chloroaniline, This compound has unique chemical properties. The synthetic route is as follows., COA of Formula: C7H8ClN

General procedure: Bi(NO3)3.5H2O (2 equiv, 0.6 mmol), Pd(OAc)2 (0.015 mmol, 5 mol percent) were added into a 25mL oven-dried Schlenk tube, the tube was evacuated and backfilled with Ar (repeated three times in 30 min). Under a counter flow of Ar, N-substituted aniline (1 equiv, 0.3 mmol) was added by syringe firstly, 1.5 mL TFE and 0.5 mL TFA were then added by disposable medical syringes. The flask was sealed and the mixture was stirred firstly at room temperature for15 min, then allowed to stir in a preheated oil bath at 90 °C for 24 h.The mixture was cooled to room temperature when the reaction was completed. Next, the solution was diluted by 10 mL ethyl acetate and filtered the insoluble matters, washed the organic phases by 5percent NaHCO3 solution after the extraction, and extracted the aqueous phases by ethyl acetate (3×15 mL) to collect organic phases. All the organic solutions were washed by brine, dried 30 min with anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude products were purified by chromatography on silica gel, eluting with ethyl acetate/petroleum ether(5/1-2/1).

According to the analysis of related databases, 7006-52-2, the application of this compound in the production field has become more and more popular.

Reference:
Article; Feng, Yi-Si; Mao, Long; Bu, Xiao-Song; Dai, Jian-Jun; Xu, Hua-Jian; Tetrahedron; vol. 71; 23; (2015); p. 3827 – 3832;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 445-13-6, 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. 445-13-6, name is 3-Chloro-4-(trifluoromethyl)aniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a solution of triphosgene (609 mg, 2.14 mmol) in toluene (5 mL) was added dropwise a solution of 3-chloro-4-(trifluoromethyl)aniline (100 mg, 0.51 mmol) and refluxed at 80 C for 0.5 h. Then the mixture was concentrated to give crude 2-chloro-4- isocyanato-l-(trifluoromethyl)benzene used in the next step without purification. To the solution of 2-chloro-4-isocyanato-l-(trifluoromethyl)benzene in THF was added (S)-3-(5- (aminomethyl)-l-oxoisoindolin-2-yl)azepane-2,7-dione (TFA salt) (59.1 mg, 0.21 mmol), followed by TEA (42 mg, 0.42 mmol). The mixture was stirred at RT for 2 h. The mixture was concentrated and purified by silica gel chromatography eluting with MeOH/DCM from 0% to 8% to give Compound 12 (29.4 mg, 28%) as a white solid. MS (ESI) m/z 509.0 [M+H]+. MR (400 MHz, DMSO-d6) delta 10.72 (s, 1 H), 9.36 (s, 1 H), 7.91 (s, 1 H), 7.70- 7.68 (m, 2 H), 7.54 (s, 1 H), 7.45-7.41 (m, 2 H), 7.06 (t, J =14 Hz, 1 H), 5.23 (dd, J =7.6, 12.8 Hz, 1 H), 4.52 (s, 2 H), 4.43 (d, J =6.0 Hz, 2 H), 3.12-3.04 (m, 1 H), 2.61-2.55 (m, 1 H), 2.28-2.22 (m, 1 H), 2.12-1.96 (m, 2 H), 1.84-1.76 (m, 1 H).

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, 3-Chloro-4-(trifluoromethyl)aniline, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; BIOTHERYX, INC.; MERCURIO, Frank; CHAN, Kyle, W.H.; SULLIVAN, Robert; ERDMAN, Paul, E.; FUNG, Leah; (105 pag.)WO2018/169777; (2018); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Synthetic Route of 108-41-8, These common heterocyclic compound, 108-41-8, name is 1-Chloro-3-methylbenzene, 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: A dried round bottomed flask equipped with a magnetic stir bar was charged with 15 mg Polymer anchored-Pd(II) C catalyst (PS-8-AQ-Pd), 2-phenyl pyridine (0.5 mmol), benzyl alcohol (1.0 mmol)and TBHP (2.0 mmol) were added to a reaction vessel. The mixture was stirred at 110 C for 8 h, then cooled to room temperature and catalyst was filtered, the filtrate was extracted with ethyl acetate(3 10 mL). The combined organic layers were extracted with water, and dried over anhydrous Na2SO4. The organic layers were evaporated under reduced pressure and the resulting crude product was purified by column chromatography by using ethylacetate/hexane (1:4) as eluent to give the corresponding ortho acylation products. The products were characterized by 1H NMR,13C NMR and HRMS.

The synthetic route of 108-41-8 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Perumgani, C. Pullaiah; Parvathaneni, Sai Prathima; Kodicherla, Balaswamy; Keesara, Srinivas; Mandapati, Mohan Rao; Inorganica Chimica Acta; vol. 455; (2017); p. 105 – 111;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 4584-46-7, These common heterocyclic compound, 4584-46-7, name is 2-Chloro-N,N-dimethylethanamine hydrochloride, 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.

2-Dimethylaminoethyl chloride hydrochloride (0.97 g, 6.70 mmol) was added to a mixture of 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (1 .00 g, 5.15 mmol) and caesiumcarbonate (5.54 g, 17.01 mmol) in dry N,N-dimethylformamide (20 mL) at 0C. After stirring for30 mm the ice-water bath was removed. The reaction mixture was stirred at room temperaturefor three days. The reaction mixture was diluted with ethyl acetate (150 mL) and washed with brine (3×100 mL). The organic layer was dried with sodium sulfate and concentrated in vacuo to afford 1 .00 g (3.41 mmol; 66% of theory) of the title compound.GO-MS (Method L9): R1 = 4.48 mm; (no mass detected)1 H NMR (300 MHz, Chloroform-d, Method M2) 6 7.78 (s, 1 H), 7.74 (s, 1 H), 4.23 (t, J = 6.8 Hz,2H), 2.76 (t, J = 6.8 Hz, 2H), 2.26 (s, 6H), 1.31 (s, 12H).

The synthetic route of 4584-46-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER ANIMAL HEALTH GMBH; KOeHLER, Adeline; WELZ, Claudia; BOeRNGEN, Kirsten; KULKE, Daniel; ILG, Thomas; KOeBBERLING, Johannes; HUeBSCH, Walter; SCHWARZ, Hans-Georg; GOeRGENS, Ulrich; EBBINGHAUS-KINTSCHER, Ulrich; HINK, Maike; NENNSTIEL, Dirk; RAMING, Klaus; ADAMCZEWSKI, Martin; BOeHM, Claudia; (269 pag.)WO2017/178416; (2017); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 13526-66-4, name is 3-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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. COA of Formula: C6H3BrClN3

In an inert atmosphere, 3.0 g (12.9 mmol) of 3-bromo-6-chloroimidazo[1 ,2-b]- pyridazine, 6.85 g (16.8 mmol) of the crude 2-stannylfuro[3,2-b]pyridine, 246 mg (1 .29 mmol) copper (I) iodide and 453 mg (0.645 mmol) bis(triphenylphosphine) palladium(ll)chloride in 100 mL of THF was stirred over night at 85C in a sealed pressure tube. The solvent was evaporated, the obtained solid was digested in dichloromethane/methanol and filtered off. The solid was washed with methanol and hexane to give 2 g of the title compound as solid material.

The synthetic route of 3-Bromo-6-chloroimidazo[1,2-b]pyridazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; EIS, Knut; PUeHLER, Florian; ZORN, Ludwig; SCHULZE, Volker; SUeLZLE, Detlev; LIENAU, Philip; HAeGEBARTH, Andrea; PETERSEN, Kirstin; BOeMER, Ulf; WO2013/149909; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 87851-77-2, 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. 87851-77-2, name is O-(3-Chloroallyl)hydroxylamine belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

The cyclohexanone derivatization method is described immediately below. Weigh about 2.00 g of sample in a vial containing 2.20 g of cyclohexanone; Add 50percent sodium hydroxide if necessary to bring pH to above 9. Stir the mixture in the capped vial at 50° C. for 2 hours. After cooling, add 8.0 g of dichloromethane and shake for one minute. Settle the mixture for 5 minutes. Take the organic phase for gas chromatographic (GC) analysis. CPHA purity and impurity profile are directly based on GC area. Hydroxylamine content is calculated based on the integration area of cyclohexanone oxime (cyclohexanoxime) peak and O-(chloro-2-propenyl)cyclohexanoxime peak.

The synthetic route of O-(3-Chloroallyl)hydroxylamine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Honeywell Corporation; US2005/85645; (2005); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 3843-97-8, name is 5-Chloro-2-ethylaniline, belongs to chlorides-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 3843-97-8, Quality Control of 5-Chloro-2-ethylaniline

A mixture of 5-chloro-2-ethylaniline (3.35 g, 21.5 mmol), p-toluensulfonic acid (12.29 g, 64.6 mmol) and water (2.15 mL) were ground in a mortar for few minutes, to obtain a homogeneous paste to which solid sodium nitrite (3.71 g, 53.8 mmol) was added and the paste ground for 10 min. Solid potassium iodide (8.94 g, 53.8 mmol) was added and the paste ground for 20 min. The paste was then dissolved in water (50 mL) and treated with sodium sulfite (10% aq. sol.), before being extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over sodium sulfate and the crude was purified by flash chromatography (hexane) to obtain the title compound as a light-yellow oil (4.35 g, 76%).1H NMR (400 MHz, DMSO-d6) delta ppm 1.12 (t, J=7.51 Hz, 3 H), 2.66 (q, J=7.53 Hz, 2 H), 7.29 – 7.35 (m, 1 H), 7.42 (dd, J=8.30, 2.20 Hz, 1 H), 7.87 (d, J=2.20 Hz, 1 H).

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; NERVIANO MEDICAL SCIENCES S.R.L.; BRASCA, Maria, Gabriella; BERTRAND, Jay, Aaron; GNOCCHI, Paola; MOTTO, Ilaria; NESI, Marcella; PANZERI, Achille; VIANELLO, Paola; WO2013/14039; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics