Month: October 2020

A common heterocyclic compound, 4863-91-6, name is 3-Chloro-5-fluoroaniline, molecular formula is C6H5ClFN, 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. 4863-91-6.

To a solution of compound 36.7 (1 eq) in toluene (50 eq) cooled in an ice water bath was added N,N,N’,N’-tetramethylethylenediamine (4 eq) and chlorotrimethylsilane (3 eq) the reaction mixture was allowed to come to rt for 30 min. Iodine (1.1 eq) was added portion wise at 10 C. After the addition of iodine was complete the reaction mixture stirred at RT for 3 h followed by diluting with EtOAc and washing with aq a2S204, dried over Na2SC>4 and concentrated in vacuo to afford to a residue. The crude iodo intermediate was dissolved in THF (19 eq) and added to a solution of 3-chloro-5-fluoroaniline (1 eq) in THF (40 eq) and sodium hydride (60% oil dispersion 1.2 eq). The reaction mixture was stirred at RT for 2 h followed by diluting with EtOAc and washing with 5% citric acid, dried over Na2SC>4 and the solvent removed in vacuo. The residue was purified by flash chromatography (10% EtOAc/Hexane to 100% EtOAc) to provide compound 36.8 (39% yield) as a white foam. EIMS (m/z): calcd. for C21H29CIFN3O4 (M++Na) 463.92, found 463.90.

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

Reference:
Patent; BIOGEN IDEC MA INC.; ERLANSON, Daniel, A.; MARCOTTE, Doug; KUMARAVEL, Gnanasambandam; FAN, Junfa; WANG, Deping; CUERVO, Julio, H.; SILVIAN, Laura; POWELL, Noel; BUI, Minna; HOPKINS, Brian, T.; TAVERAS, Art; GUAN, Bing; CONLON, Patrick; ZHONG, Min; JENKINS, Tracy, J.; SCOTT, Daniel; SUNESIS PHARMACEUTICALS, INC.; LUGOVSKOY, Alexey, A.; WO2011/29046; (2011); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

60811-21-4,Some common heterocyclic compound, 60811-21-4, name is 4-Bromo-2-chloro-1-fluorobenzene, molecular formula is C6H3BrClF, 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.

To a solution of dissoprppylamine (5.1 mL, 36.0 mmol, 1.5 eq.) in anhydrous THF (15 mL) was added n-BuLi (19.2 mL, 28.8 mmol, 1.2eq.) dropwise at -78C under N2 atmosphere, then was added the 4-bromo-2-chloro-l-fluorobenzene (5 g, 24.0 mmol, 1.0 eq.) at -78C 1 h later. The mixture was stirred at -78C for 45 minutes, then was added DMF (2.8 mL, 36.0 mmol, 1.5 eq. ), warmed to -30C until TLC showed that the reaction was completed. The reaction was quenched with H20 (100 mL), then adjusted to pH 2-3, extracted with EA (50 mLx3). The combined organic layers were washed with brine, dried over anhydrous Na2S04 and evaporated. The residue was purified by column chromatography (PE/EA=100: 1) to provide 5-bromo-3-chloro-2-fluoroben low solid.

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

Reference:
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; QIAN, Shawn; (297 pag.)WO2018/229543; (2018); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 108-70-3, name is 1,3,5-Trichlorobenzene, I believe this compound will play a more active role in future production and life. 108-70-3

Example 4; Preparation method of 1,3,5-trifluorobenzene; 500 g of 1,3,5-trichlorobenzene, 1180 ml of sulpholane, 10.7 g of 3-nitrodimethylbenzamide and 640 g of dry KF were initially charged in an autoclave, then 48 g of CNC catalyst were added and the autoclave was sealed. The mixture was heated to 220 C. for 48 h. During the reaction, a maximum total pressure of 8 bar arose. Subsequently, the mixture was cooled to 20 C. The product was distilled off initially at standard pressure, later under reduced pressure. 310 g of a colourless liquid having a proportion of 87% by weight of 1,3,5-trifluorobenzene (74% of theory) and 8.8% by weight of difluorochlorobenzene (6.7% by weight of theory) were obtained. 1,3,5-Trifluorobenzene and difluorochlorobenzene can be separated distillatively in a known manner.

The chemical industry reduces the impact on the environment during synthesis 108-70-3. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Pleschke, Axel; Marhold, Albrecht; US2006/9643; (2006); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding some certain compound to certain chemical reactions, such as: 96558-78-0, name is 3-Bromo-5-chlorophenylamine, 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 96558-78-0. 96558-78-0

To a solution of 3 -bromo-5-chloro- aniline (500 mg, 2.42 mmol) in l,4-dioxane (10 ml) and H20 (1 ml) was added 4, 4,5,5- tetramethyl-2-(2-methylprop- l-enyl)- 1 ,3,2-dioxaborolane (529 mg, 2.90 mmol), Pd(dppf)Cl2 (177 mg, 0.24 mmol) and Cs2C03 (2.37 g, 7.26 mmol). The RM was heated to 120 C for 12 h under N2. The solution was concentrated in vacuo. The residue was purified by FCC (25 % EtOAc in petroleum ether) to give the title compound as a green oil (Y = 41 %). ‘H NMR (400 MHz, DMSO-rf6) d ppm 6.42 (t, J= 2 Hz, 1H), 6.37 (s, 1H), 6.34 (s, 1H), 6.08 (s, 1H), 5.35 (s, 2H), 1.83 (s, 3H), 1.80 (s, 3H).

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 3-Bromo-5-chlorophenylamine.

Reference:
Patent; NODTHERA LIMITED; HARRISON, David; WATT, Alan Paul; BOCK, Mark G.; (334 pag.)WO2019/121691; (2019); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

The chemical industry reduces the impact on the environment during synthesis 126764-17-8, name is 1-Chloro-6,6-dimethylhept-2-en-4-yne, I believe this compound will play a more active role in future production and life. 126764-17-8

29 kg of N-methyl-1 -naphthalene methylamine hydrochloride was charged into a reactor containing 70.4 liters of dimethylformamide and 11 liters of water, under stirring. The contents were stirred for 15 minutes for clear dissolution and 11 kg of sodium carbonate was added to it. The reaction mass was cooled to 13 EPO C and 22 kg of 1-chloro-6,6-dimethyl-2-heptene-4-yne was added slowly at 11 to 14 C. The reaction mixture was stirred at 12 to 14 0C for 60 minutes and then heated to 55 0C. The reaction mass was maintained at 60 C for 5 hours and reaction completion was confirmed by thin layer chromatography. The reaction mass was cooled to room temperature and 99 liters of water was added. Reaction mass was extracted three times with a total of 75 liters of dichloromethane (3×25 liters). Total organic layer was washed twice with 88 liters of water (2×44 liters); 18 liters of water was charged to the final organic layer and was cooled to 13 0C. Reaction mass pH was adjusted to 0.2 by adding 15 liters of 36% aqueous hydrochloric acid and stirring for 30 minutes. The organic layer was separated and washed three times with a total of 267 liters of water (3chi89 liters). Final organic layer was transferred into a reactor and the solvent was distilled completely below 45 C. 11.8 liters of petroleum ether was charged and the solvent distilled completely at below 50 C. Again 68 liters of petroleum ether was charged and heated to reflux. The mass was stirred at reflux for 30 minutes and cooled to 50 C. The solid thus formed was allowed to settle for 60 minutes and the top petroleum ether layer was decanted. The decantation process was repeated two more times. Finally 44 liters of petroleum ether was charged, heated to reflux, maintained for 30 minutes at reflux and then cooled to 25 C. The contents were stirred for 60 minutes at 20 to 25 0C and centrifuged to recover the solid. The centrifuged solid was washed twice with petroleum ether (2×16 liters) and spin- dried for about 60 minutes to get 29.3 kg of crude terbinafine hydrochloride as a semi-dry solid.

The chemical industry reduces the impact on the environment during synthesis 126764-17-8. I believe this compound will play a more active role in future production and life.

Reference:
Patent; DR. REDDY’S LABORATORIES LTD.; DR. REDDY’S LABORATORIES, INC.; WO2007/44273; (2007); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

These common heterocyclic compound, 2613-34-5, name is 3-Chloro-2,4-difluoroaniline, 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. 2613-34-5

1,3 -dimethyl-4-(N-(3 -methyloxetan-3 -yl)sulfamoyl)- 1 H-pyrrole-2-carboxylic acid (500 mg, 1.73 mmol), 3-chloro-2,4-difluoroaniline (0.57 g, 3.47 mmol) and HATU (0.88 g, 2.31 mmol) were dissolved in DMF (2 mL) containing DIPEA (0.69 mL, 3.98 mmol). The reaction mixture wasstirred at 65C for 28 hours and at room temperature for 60 hours. The reaction mixture was purified using silica gel column chromatography (ethyl acetate in heptane from 10 to 70%). The desired fractions were combined and evaporated to afford a light brown oil which solidified while standing. The solid was recrystallized from ethanol (5 mL) to afford a white solid which was filtered and washed with ethanol (1 mL). The white solid was dried overnight in vacuo,resulting in compound 243 (318 mg) as off white solid. Method D: Rt: 1.73 mm mlz: 432.0 (MH) Exact mass: 433.1 .?H NMR (400 MHz, DMSO-d6) oe ppm 1.52 (s, 3 H), 2.37 (s, 3 H), 3.73(s, 3 H), 4.11 (d, J=6.4 Hz, 2 H), 4.61 (d, J=5.9 Hz, 2 H), 7.35 (td, J=9.0, 2.0 Hz, 1 H), 7.47 (s, 1H), 7.67 (td, J=8.7, 5.8 Hz, 1 H), 7.91 (br. s., 1 H), 10.03 (br. s., 1 H).

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 2613-34-5.

Reference:
Patent; JANSSEN R&D IRELAND; VANDYCK, Koen; HACHE, Geerwin, Yvonne, Paul; LAST, Stefaan, Julien; MC GOWAN, David, Craig; ROMBOUTS, Geert; VERSCHUEREN, Wim, Gaston; RABOISSON, Pierre, Jean-Marie, Bernard; WO2014/184350; (2014); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 6940-78-9 name is 1-Bromo-4-chlorobutane, 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. 6940-78-9

Methanol (149 L) , 7-hydroxy-lH-guinolin-2-one (14.87 kg), and potassium hydroxide (6.21 kg) were mixed in a reaction vessel, and the resulting mixture was stirred. After dissolution, l-bromo-4-chlorobutane (47.46 kg) was added thereto, and the resulting mixture was stirred under reflux for seven hours.Thereafter, the mixture was stirred at 10 C for one hour. The precipitated crystal was centrifuged and washed with methanol (15 L). The wet crystal was collected and placed in a tank. Water (149 L) was added thereto, followed by stirring at roomtemperature. After centrifugation, the result was washed with water (30 L). The wet crystal was collected and placed in a tank. After adding methanol (74 L), the mixture was stirred under reflux for one hour, cooled to 10 C, and then stirred. The precipitated crystal was centrifuged and washed with methanol (15 L). The separated crystal was dried at 60 C to obtain 7- (4- chlorobutoxy) -lH-quinolin-2-one (15.07 kg).

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

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; KANEKO, Daiki; MATSUDA, Takakuni; HOSHIKA, Yusuke; WO2013/162048; (2013); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

33863-76-2, 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 33863-76-2 as follows.

A solution of 1-bromo-3-chloro-5-fluorobenzene (50.0 g, 239 mmol) in DMF (300 ml.) was treated with sodium methoxide (15.5 g, 286 mmol) and the reaction was stirred overnight at rt. The mixture was diluted with ethyl acetate (500 mL) and washed with water (700 mL). The organic layer was isolated, washed with brine, dried over magnesium sulfate, filtered, and concentrated to give 51.0 g of the title compound which was used without purification. 1H NMR (DMSO-c/6) delta 7.23 (t, 1 H), 7.13 – 7.15 (m, 1 H), 7.05 (t, 1 H), 3.77 (s, 3 H).

According to the analysis of related databases, 1-Bromo-3-chloro-5-fluorobenzene, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2008/157273; (2008); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

433-94-3, 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. 433-94-3, name is 2-Chloro-6-(trifluoromethyl)aniline belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

A) 15 g of hydrochloric acid (0.15 mol) are added to the reaction apparatus,After cooling, 9.2 g (0.047 mol) of 2-chloro-6-trifluoromethylaniline was dropwise added to the system,Dropping added insulation reaction 60min,Then sodium nitrite solution 13.5g (0.09mol) was added dropwise to the system,Process temperature 3 ,Dropping added insulation reaction 2h; B) 32 g (0.32 mol) of hydrochloric acid was added to the above system,1.6 g (0.01 mol) of copper sulfate,Stirring until dissolved,Then 33.84 g (0.141 mol) of sodium bisulfite solution was added dropwise,After the addition was complete, the temperature was raised to 60 C. and incubated for 1.5 hours.The reaction is completed and extracted with methylene chloride, separated, the organic phase is dried, filtered, and the solvent is removed to give 2-chloro-6-trifluoromethylbenzenesulfonyl chloride;

The synthetic route of 433-94-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Yellow River Delta Jingbo Chemical Institute Co., Ltd.; Yu Long; Yao Gang; Chang Jinlei; Chen Zhimin; Liu Kefeng; Fan Qiyan; (6 pag.)CN106478464; (2017); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Adding some certain compound to certain chemical reactions, such as: 933190-51-3, name is 8-Bromo-6-chloroimidazo[1,2-b]pyridazine, 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 933190-51-3. 933190-51-3

[00350] To a 0C mixture of benzyl alcohol (0.3 mL, 2.98 mmol) in THF (40 mL) was added sodium hydride (0.25 g) in an ice-water bath under a N2 atmosphere. The reaction mixture was stirred for 30 minutes at 0C, and then a solution of 8-bromo-6-chloroimidazo[1,2-b]pyridazine (462 mg, 1.99 mmol) in THF (50 mL) was added in dropwise. The reaction mixture was warmed to rt slowly and stirred for 1 hour, then quenched with saturated aqueous sodium chloride solution (50 mL) and the resulting mixture was extracted with ethyl acetate (500 mL). The organic phase was washed with water (50 mL) and saturated aqueous sodium chloride solution (50 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v) = 1/2) to give the title compound as an oil (0.26 g, 50%). The compound was characterized by the following spectroscopic data:MS-ESI: (ESI, pos.ion)m/z: 260.1 [M+1].

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 8-Bromo-6-chloroimidazo[1,2-b]pyridazine.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; CHENG, Changchung; ZHANG, Yingjun; LIU, Bing; LONG, Bohua; CHEN, Yu; CHENG, Zhixin; (182 pag.)WO2016/8433; (2016); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics