Category: 1996-29-8

Synthetic Route of 1996-29-8, 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. 1996-29-8 name is 1-Bromo-4-chloro-2-fluorobenzene, 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.

1. Preparation of 3-bromo-6-chloro-2-fluorophenol; A solution of 1-bromo-4-chloro-2-fluorobenzene (20.4 g, 0.100 mol) in tetrahydrofuran (THF; 50 mL) was slowly added to lithium diisopropyl amide (LDA; 0.125 mol) in THF (600 mL) at -50 C. After addition the solution was warmed to -20 C. and then cooled to -50 C. and a solution of trimethyl borate (13.5 g, 0.130 mol) in tetrahydrofuran (20 mL) was added slowly and the temperature was warmed to -20 C. The mixture was then cooled to -70 C. and solution of peracetic acid (32% in acetic acid, 0.150 mol) was slowly added and the mixture was warmed to ambient temperature. Water (250 mL) was added and solution extracted with ethyl acetate (2×200 mL). The combined organic phases were dried and concentrated. The black oil was purified by column chromatography (20% ethyl acetate in hexanes) to give 3-bromo-6-chloro-2-fluorophenol (14.1 g, 0.063 mol): 1H NMR (CDCl3): delta 7.05 (m, 2H), 5.5 (bs, 1H).

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

Reference:
Patent; Balko, Terry W.; Schmitzer, Paul R.; Daeuble, John F.; Yerkes, Carla N.; Siddall, Thomas L.; US2007/179060; (2007); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, A new synthetic method of this compound is introduced below., Recommanded Product: 1996-29-8

General Procedure: In a 2OmL tube equipped with a stir bar added l-bromo-4-chloro-2- fluorobenzene (Ig, 4.77mmol), ‘butyl- 1-piperazinecarboxylate (1.74g, 9.55mmol), palladium acetate (0.107g, 0.48mmol), 2-ditbutylphosphenylbiphenyl (0.143g, 0.48mmol), sodium tert- butoxide (0.688g, 7.16mmol) and toluene (10 mL). The reaction vessel was sealed and placed in a microwave oven at 15O0C for 15 min. The reaction mixture was filtered though Diatomaceous earth. The filtrate was diluted with ethyl acetate (50 mL), sequentially washed with water (3 x 5OmL) and brine (5OmL) in a separation funnel. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified on silica gel using hexanes: ethyl acetate= 93: 7 to hexanes: ethyl acetate= 95: 5 in a gradient fashion, to isolate the desired product as yellow oil (639mg, 43%). 1H NMR (300 MHz, CDCl3): delta 7.03 (m, 2H), 6.83(m, IH), 3.57 (t, 4H)5 2.95 (t, 4H), 1.46 (s, 9H).

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; ASTRAZENECA AB; NPS PHARMACEUTICALS, INC.; WO2007/87135; (2007); A2;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 1996-29-8, 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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of 1-bromo-4-chloro-2-fluorobenzene (5 g, 23.87mmol) in tetrahydrofuran (40 mL) was cooled to -78 C was added LDA, 2M inTHF/heptane/ethylbenzene (14.92 mL, 29.8 mmol) dropwise and the reaction mixture was stirred at this temperature for 30 mm. The solution was allowed to warm to -20 C and stirred for 30 mm. The reaction was cooled to -78 C and trimethyl borate (3.47 mL, 31.0 mmol) dissolved in THF (5 mL) was addeddropwise and the reaction mixture was warmed to -20 C and stirred for 1 h. The reaction mixture was cooled to -78 C and peracetic acid (16 mL, 84 mmol) was added dropwise and the mixture allowed to warm to rt and stirred for 12 h. The reaction mixture was cooled to 0 C and quenched with 5% aqueous ammonium chloride and extracted with ethyl acetate (2X50 mL). The combined organiclayers were washed with brine (50 mL). The organic layer was dried over sodium sulphate and concentrated under reduced pressure to yield 3-bromo-6-chloro-2- fluorophenol (4.99 g, 18.25 mmol, 76% yield) as yellow oil. LCMS (ESI) m/e 225.1 [(M+H), calcd for C6H4BrC1FO 224.9]; LC/MS retention time (method G): tR = 0.87 mm.

The synthetic route of 1-Bromo-4-chloro-2-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; VRUDHULA, Vivekananda M.; PAN, Senliang; RAJAMANI, Ramkumar; MACOR, John E.; BRONSON, Joanne J.; DZIERBA, Carolyn Diane; NARA, Susheel Jethanand; KARATHOLUVHU, Maheswaran Sivasamban; WO2015/38112; (2015); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Electric Literature of 1996-29-8,Some common heterocyclic compound, 1996-29-8, name is 1-Bromo-4-chloro-2-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.

1-bromo-4-chloro-2-fluorobenzene (61 g, 291 mmoles), 2,6-dimethoxyphenylboronic acid (50.4 g, 277 mmoles), K2 CO3 (60.4 g, 437 mmoles) and Pd (PPh3) 4 (10.1 g, 8.7 mmoles)Put in a round bottom flask,And then dissolved in 500 ml of THF and 200 ml of distilled water,And the solution was refluxed and stirred at 60 C for 12 hours.When the reaction is complete,The aqueous layer was removed and passed through column chromatography (hexane: DCM 20%)Process the remainder to obtain 38 grams of intermediate 1(51%).

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-4-chloro-2-fluorobenzene, its application will become more common.

Reference:
Patent; SAMSUNG SDI CO., LTD.; Kang, Dong Min; Kim, Jun Seok; Lui, Jinhyun; Lee, Byoungkwan; Lee, Sangshin; Won, Jonswoo; Lee, Namheon; Jung, Sung Hyun; Jung, Ho Kuk; (107 pag.)TW2019/43698; (2019); A;,
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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Safety of 1-Bromo-4-chloro-2-fluorobenzene

Carbazole (20.0 g, 119.6 mmol) and KF-alumina (30.0 g, 179.4 mmol) under a stream of nitrogenAnd 18-crown-6 (6.3 g) was placed in 120 mL of dimethyl sulfoxide (DMSO; Dimethylsulfoxide) solvent and stirred with heating.1-Bromo-4-chloro-2-fluorobenzene (25.1 g, 119.6 mmol) was added under reflux.After stirring for 8 hours, it was cooled to normal temperature, and the resulting solid was filtered to obtain a compound of the formula 2-2-A (35.1 g, yield 83%).

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 1996-29-8.

Reference:
Patent; Co., Ltd. LG Chemical; Han Meilian; Li Dongxun; Xu Jingwu; Zhang Fenzai; Xu Dongxu; Zheng Minyou; (51 pag.)CN108218802; (2018); A;,
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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 1-Bromo-4-chloro-2-fluorobenzene

General procedure: (2-Bromo-5-chloro-phenyl)hydrazine (6) A 250 mLround-bottom flask was charged with 1-bromo-4-chloro-2-fluoro-benzene (8.5 mL,68.0 mmol), hydrazine monohydrate (13 mL, 270 mmol) and dimethylsulfoxide (25mL) and the solution was stirred at 70 C for 3 days. The reaction was then cooled to room temperature and water (200 mL) was added. The precipitate was collected by filtration and dried under vacuum for 16 hours to give (2-bromo-5-chloro-phenyl)hydrazine (14.5g, 65 mmol, 96% yield) as a white solid. LCMS ES+ m/z = 221.0 [M+H]+.

According to the analysis of related databases, 1996-29-8, the application of this compound in the production field has become more and more popular.

Reference:
Article; Rene, Olivier; Fauber, Benjamin P.; Tetrahedron Letters; vol. 55; 4; (2014); p. 830 – 833;,
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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 1-Bromo-4-chloro-2-fluorobenzene

To a stirred solution of 1-bromo-4-chloro-2-fluorobenzene (5 g, 23.87 mmol) in tetrahydrofuran (40 mL) cooled to -78 C was added LDA (14.92 mL, 29.8 mmol) dropwise. The reaction mixture was stirred at this temperature for 30 min. thenallowed to warm to -20 C and stirred for 30 min. The reaction was then cooled to -78 C and trimethyl borate (3.47 mL, 31.0 mmol) dissolved in THF (5 mL) was added dropwise. The reaction mixture was warmed to -20C and stirred for 1 h. The reaction mixture was then cooled to -78 C and peracetic acid (16 mL, 84 mmol) as slowly added dropwise. The mixture was allowed to warm to rt and stirred for 12 h. The reaction mixture was again cooled to 0 C and quenched with 5% ammonium chloride The solution was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-bromo-6-chloro-2-fluorophenol (4.99 g, 18.25 mmol, 76 % crude yield) as ayellow oil. The material was carried forward without further purification.

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 1996-29-8.

Reference:
Patent; Bristol – Myers Squibb Company; Vivekanand, M.Burda; Pan, Senrian; Ramkumar, Rajamani; Sushil, Jetanand Nara; Maheswaran, Shibasanban Calatrava; Tarun Kumar, Meishar; Jonathan, L. Ditta; Carolyn, Diane Jiaba; John, J. Bronson; John, E. Maco; (232 pag.)JP2015/528018; (2015); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Reference of 1996-29-8, 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. 1996-29-8, name is 1-Bromo-4-chloro-2-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.

N. 2-CHLORO-5-CYCLOPROPYL-6-FLUOROANILINE The preparation is an adaptation of a method described in Tetrahedron Lett, Vol. 37, p. 6551 (1996). A solution of lithium DIIOSOPROPYL amide is generated by adding n-BuLi (360 mL of 2 M solution in THF) to diisopropylamine (73 g, 0.722 mol) in 500 mL of anhydrous THF while a reaction temperature OF-60C is maintained by cooling in dry-ice acetone bath. After stirring for 30 minutes, 1-bromo-4-chloro-2-fluorobenzene (75 g, 0.36 mol) is added and stirring maintained AT-70C for 2 hours. The cold solution is then transferred, via a canula, under an inert atmosphere to a suspension of solid C02 (100 g, excess) in anhydrous ET2O. The mixture is allowed to warm to room temperature with stirring and then the solvent removed by rotary evaporator. The residual solid is treated with 1 N HCI solution until PH = 3.0 and the mixture is filtered. The white solid that is obtained is suspended in 1000 mL of 2 N HCI solution and stirred for an additional 1 hour. The suspension is filtered to collect a white solid which is air dried, suspended in 100 mL of hexanes and collected to give 2-CHLORO-5-BROMO-6-FLUOROBENZOIC acid. 2-Chloro-5-bromo-6-fluorobenzoic acid (91 g, 0.36 mol) is suspended in CH2CI2 (200 mL) and treated with oxalyl chloride (51 g, 0.40 mol) by dropwise addition, immediately followed by the addition of several drops (0.1 mL) of DMF. The mixture is stirred at room temperature for 3 hours during which time the solid completely dissolves and a clear solution is obtained. The solvent is removed by rotary evaporator and the residue is added to 1000 mL of ammonium hydroxide while stirring at 0C. The product is collected by filtration and washed with water to give 2-chloro-5-bromo-6-fluorobenzamide as a white solid. A solution of sodium methoxide is generated by treating metallic sodium (18 g, 0.78 mol) with 1000 mL of anhydrous methanol by dropwise addition under an inert atmosphere. After the metal is completely consumed the solution is heated at reflux temperature for 30 minutes and then cooled to room temperature. 2-Chloro-5-bromo-6-fluorobenzamide (65 g, 0.26 mol) is added and stirring continued for an additional 30 minutes at room temperature. N-BROMOSUCCINIMIDE (92 g, 0.52 mol) is then slowly added via a powder addition funnel. The reaction mixture is warmed to 60C for 30 minutes during which time foaming is observed. The reaction mixture is cooled to room temperature and most of the solvent is removed by rotary evaporator. The residue is partitioned between EtOAc (1000 mL) and water (1000 mL). The organic layer is separated and washed with water (5 x 500 mL) and then brine (2 x 500 mL). The organic layer is dried (MGS04), filtered and concentrated by rotary evaporator to GIVE N- (2-CHLORO-5-BROMO-6-FLUOROPHENYL)-CARBAMIC acid methyl ester as a light yellow solid (m. p. 107-112C). N-(2-chloro-5-bromo-6-fluorophenyl)-carbamic ester methyl ester (8.65 g, 30.6 MMOL), cyclopropylboronic acid (3.16 g, 36.7 MMOL), potassium phosphate (22.8 g, 107 MMOL), palladium acetate (343 mg, 1.53 MMOL) and tricyclohexylphosphine (858 mg, 3.06 MMOL) are combined and stirred in a two-phase solution comprised of toluene (350 mL) and water (75 mL). The mixture is degassed by repeated alternating application of vacuum and positive nitrogen pressure (10 x). The mixture is heated to 95C for 4 days and then cooled to room temperature. The reaction mixture is partitioned between EtOAc (500 mL) and water (500 mL). The organic phase is washed with water (2 x 250 mL), brine (500 mL) and then dried (MGS04) and concentrated by rotary evaporator. The crude product is purified using flash chromatography (7-14% EtOAc/hexanes). After evaporation of the appropriate fractions the product is further purified by treating a solution in ET20 (100 mL) with charcoal, followed by filtration through Celite and evaporation. N- (2-chloro-5- cyclopropyl-6-fluorophenyl)-carbamic acid methyl ester is obtained as a white crystalline solid (m. p. 100-102C). N-(2-CHLORO-5-CYCLOPROPYL-6-FLUOROPHENYL)-CARBAMIC acid methyl ester (2.3 g, 9.4 MMOL) is dissolved in MeOH (50 mL), water (50 mL) and 30% NAOH solution (50 mL). The reaction mixture is heated to reflux temperature for 3 days and then cooled to room temperature. The reaction is concentrated by rotary evaporator to remove most of the methanol and then partitioned between ET20 (250 mL) and water (250 mL). The aqueous phase is extracted again with ET20 (150 mL) and the-combined organic layers washed with brine (250 mL), dried and concentrated by rotary evaporator. The crude product is purified by bulb-to-bulb distillation. 2-Chloro-5-cyclopropyl-6-fluoroaniline is isolated as a colorless oil (b. p. 120-135C at-20 mm of Hg).

The synthetic route of 1-Bromo-4-chloro-2-fluorobenzene has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2004/48314; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Application of 1996-29-8,Some common heterocyclic compound, 1996-29-8, name is 1-Bromo-4-chloro-2-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.

Under a nitrogen atmosphere, 104.7 g of 2-fluoro-4-chlorobromobenzene, 400 ml of THF and 67.3 g of potassium t-butoxide were added to a 1 L three-necked flask.After cooling to -60 C, 300 mL of n-butyl lithium solution (2 mol / L) was added dropwise, and the addition was completed -50 to -60 CAfter heat preservation for 1 h, the temperature was raised to -30 C, and then 172.6 g of tributyl borate was added dropwise.After the completion of the dropwise addition, the temperature was naturally raised to room temperature for 2 hours.The reaction solution is acidified with hydrochloric acid, extracted with petroleum ether, and washed with water.Concentrated to a white solid a-1, 75.1 g, Y = 86.1%,LC = 98.15%. 2) Synthesis of a-2: under nitrogen protection,Add a-1 41.9g to a 250ml three-necked bottle.4-bromo resorcinol37.8g, potassium carbonate 27.6g,TBAB 2.0g, Pd(0) 0.5g, ethanol 100mL, water 50mL,After stirring at reflux for 3 h, the reaction solution was acidified with dilute hydrochloric acid.Extracted with ethyl acetate and concentrated.Recrystallization from 2 times ethanol gave a white solid a-2.38.5 g, Y = 80.7%, GC = 98.78%. 3) Synthesis of a-3: under nitrogen protection,Add a-223.9g to a 100ml three-necked bottle.DMF 70mL, 60% sodium hydride 8.0g,Reflow reaction for 0.5 h,The reaction solution was poured into ice water, neutralized with dilute hydrochloric acid, and extracted with ethyl acetate, and evaporated to give a yellow solid a-3, 20.9 g,GC=98.61% 4) Synthesis of a-4: A-320.9 g was sequentially added to a 100 ml three-necked flask.60 mL of dichloromethane,21.7 g of trimethylchlorosilane, reacted at room temperature for 0.5 h, concentrated,A yellow solid a-4, 27.8 g, Y = 100%, GC = 98.65%. 5) Synthesis of a-5: under nitrogen protection,Add a-423.3g to a 250 mL three-necked flask.THF 100ml, potassium t-butoxide 10.8g, after cooling to -50 C,60 mL of n-butyllithium solution (2 mol/L) was added dropwise.After the addition is completed, the temperature is kept at -50 to -40 C for 1 h.After heating to -30 C, 27.6 g of tributyl borate was added dropwise.After the completion of the dropwise addition, the temperature was naturally raised to room temperature for 2 hours. The reaction mixture was acidified with hydrochloric acid, extracted with EtOAc EtOAc.Y = 74.2%, LC = 98.66%. 6) Synthesis of a-6: Under nitrogen protection, 4-bromo resorcinol 9.5 g, a-5 17.8 g, potassium carbonate 13.8 g, TBAB 1.0 g were sequentially added to a 100 ml three-necked flask.Pd(0)0.2g, ethanol 50mL, water 20mL, reflux and stirring for 5h,The reaction solution was acidified with dilute hydrochloric acid, extracted with toluene, and concentrated.Recrystallization from 2 times ethanol gave a pale yellow solid a-6.13.1 g, Y = 71.9%, GC = 99.18%. 7) Synthesis of a-7: A-6 10.9 g was added to a 100 ml three-necked bottle in turn.50mL of dichloromethane, 9.4g of tetrabutylammonium fluoride,The reaction was refluxed for 1 h, washed with water and concentrated to give a pale yellow solid a-7.8.1 g, Y = 92.0%, LC = 98.76%. 8) Synthesis of a: under nitrogen protection,Add a-75.8g to a 100ml three-necked bottle.50 mL of dichloromethane and 9.1 g of triethylamine.The polymerization inhibitor is 0.01 g of hydroquinone, and a mixed solution of 7.5 g of methacryloyl chloride and 15 mL of dichloromethane is added dropwise in an ice water bath, and the mixture is naturally added to room temperature and stirred for 0.5 h after the dropwise addition.The reaction solution is acidified with dilute hydrochloric acid, washed with water and concentrated.Recrystallization from 1x ethanol and 2 times n-heptane mixed solvent,Purified by silica gel column to obtain product a, 5.2g, Y=52.5%,LC = 99.90%.

The synthetic route of 1996-29-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Xi’an Ruili Electronic Materials Co., Ltd.; Li Chao; Zhao Wen; Zhang Yanli; Jin Linuo; (35 pag.)CN109503534; (2019); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Some common heterocyclic compound, 1996-29-8, name is 1-Bromo-4-chloro-2-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. SDS of cas: 1996-29-8

Under an argon atmosphere,9H-carbazole (9.3 g), 1-bromo-4-chloro-2-fluorobenzene (23.3 g), cesium carbonate (36.2 g) and DMF (222 mL) were stirred at 150 C. for 7 hours. Water was added at room temperature, and the resulting mixture was extracted with ethyl acetate. The organic layer was purified by silica gel chromatography, and the solvent was removed to obtain 9- (2-bromo-5-chlorophenyl) carbazole as a white solid (11.4 g, yield 58%).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1996-29-8, its application will become more common.

Reference:
Patent; IDEMITSU KOSAN COMPANY LIMITED; HAKETA, TASUKU; ITO, HIROKATSU; KUDO, YU; (149 pag.)JP2018/108939; (2018); A;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics