Category: 399-94-0

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. 399-94-0, name is 1-Bromo-2,5-difluorobenzene, A new synthetic method of this compound is introduced below., category: bromides-buliding-blocks

2.0 M Isopropyl magnesium chloride solution in THF (163mL, 324.3 mmol) was added to a solution of 2-bromo-l,4-difluorobenzene (62.5 g, 324.3 mmol) in THF (350mL) at -40C and stirring was continued at 5C for 1 h. tert- utyl 2- oxopyrrolidine-l-carboxylate(Step-l)(73 g, 392 mmol) in THF(150mL) was added dropwise to above reaction mixture at -40C and stirring was continued at 10C for 2 h. Reaction mixture was quenched with saturated NH4CI solution, extracted with EtOAc, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford 76 g of the title compound.

The synthetic route of 399-94-0 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DR. REDDY’S LABORATORIES LTD.; SASMAL, Pradip Kumar; AHMED, Shahadat; TEHIM, Ashok; PRADKAR, Vidyadhar; DATTATREYA, Prasanna M.; MAVINAHALLI, Nanjegowda Jagadeesh; WO2013/88256; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 399-94-0,Some common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, molecular formula is C6H3BrF2, 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 the protection of nitrogen, 2,5-difluorobromobenzene (15.05g, 78mmol) is dissolved in dry toluene (50 ml), lowering the temperature to ice salt bath -10 C following, dropwise adding isopropyl magnesium chloride/tetrahydrofuran solution of lithium chloride (66 ml, 1.3 mol/L), maintained at about -10 C stirring 1 hour. the1D (10g, 39mmol) dissolved in dry tetrahydrofuran (100 ml) in, is dropped is added to the reaction solution, maintaining the temperature -10 C, canada finishes, to react at room temperature for 4 hours. The temperature dropped to about -10 C, dropwise adding saturated ammonium chloride solution (40 ml), stirring 10 minutes, for 3 mol/L hydrochloric acid solution to adjust pH value to 5 – 6, layered, 3rd phase for methyl tert-butyl ether (50mL × 2) extraction, the combined organic phase, saturated sodium chloride solution (30mL × 2) washing, drying of the organic phase by adding anhydrous sodium sulfate, filtered, concentrated, column chromatography (petroleum ether/ethyl acetate=50:1 – 8:1 (v/v)), get the yellow solid1E(10.1g, 83.5% yield).

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-2,5-difluorobenzene, its application will become more common.

Reference:
Patent; SICHUAN HAISCO PHARMACEUTICAL CO., LTD; ZHANG, CHEN; FAN, JIANG; LI, CAI-HU; WEI, YONG-GANG; (99 pag.)TW2017/8222; (2017); A;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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 399-94-0, COA of Formula: C6H3BrF2

Step 1 : tert-Butyi 4-(2,5-difluorophenyl)piperazine-l-carboxylate (0991) [00346] To a solution of A19-1 (500 mg, 2.59 mmol, 1.0 eq), A19-1A (579 mg, 3.11 mmol, 1.2 eq), BINAP (161 mg, 0.259 mmol, 0.1 eq), f-BuONa (498 mg, 5. 18 mmol, 2.0 eq) and Pdi(dba)3 (119 mg, 0.130 mmol, 0.05 eq) in toluene (5 mL). The reaction mixture was stirred at 110 C for 16 hours. The reaction mixture was concentrated under reduced pressure. The mixture was diluted with water (10 mL) and the resultant mixture was extracted with DCM (30 mL * 3). The combined organic layers were dried over NaiSOzt, filtered and concentrated to dryness under reduced pressure. The residue was purified by column chromatography over silica gel (petroleum ether: ethyl acetate = 1 : 0 to 10: 1) to afford the title compound (400 mg, 52% yield) as a yellow solid. NMR (400MHz, COC -d) delta 7.01 – 6.90 (m, 1H), 6.66 – 6.56 (m, 2H), 3.65 – 3.53 (m, 4H), 3.07 – 2.93 (m, 4H), 1.48 (s, 9H).

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-2,5-difluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; VIVACE THERAPEUTICS, INC.; LIN, Tracy Tzu-Ling Tang; KONRADI, Andrei W.; VACCA, Joseph; SHEN, Wang; COBURN, Craig; (231 pag.)WO2017/58716; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, molecular formula is C6H3BrF2, 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. Product Details of 399-94-0

A solution of isopropylmagnesium chloride in THF (2M, 604 mL) was added dropwise to a solution of 2-bromo-1,4-difluorobenzene (244.7 g) in THF (1 L) that had been cooled to -50C. After completion of the dropwise addition, the temperature was warmed to 0C while stirring for 1 h. The reaction mixture was cooled to -50C again. To the reaction mixture was added a solution of 4-chloro-N-methoxy-N-methylbutyramide (100 g) in THF (200 mL) dropwise under stirring, and gradually warmed to 30C and then continuously stirred at 30C for 3h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The collected organic phase was washed with water and then a saturated saline solution. The organic layer was separated, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to afford the title compound (101 g). 1H NMR (400 MHz, CDCl3) delta 7.59-7.55 (m, 1H), 7.26-7.20 (m, 1H), 7.17-7.11 (m, 1H), 3.68-3.65 (m, 2H), 3.20-3.16 (m, 2H), 2.25-2.19 (m, 2H). m/z=219[M+1]+.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 399-94-0, its application will become more common.

Reference:
Patent; Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Centaurus BioPharma Co., Ltd.; Lianyungang Runzhong Pharmaceutical Co., Ltd.; ZHU, Li; HU, Yuandong; WU, Wei; DAI, Liguang; DUAN, Xiaowei; YANG, Yanqing; SUN, Yinghui; HAN, Yongxin; PENG, Yong; KONG, Fansheng; LUO, Hong; YANG, Ling; XU, Hongjiang; GUO, Meng; ZHONG, Zhaobai; WANG, Shanchun; (80 pag.)EP3533796; (2019); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 399-94-0, name is 1-Bromo-2,5-difluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 399-94-0

A tetrahydrofuran (30 ml) solution of 1-bromo-2,5-difluorobenzene (1.08 ml, 9.60 mmol) was stirred at -78C, followed by the addition of a hexane solution (7.32 ml, 11.5 mmol) of n-butyl lithium. To the reaction mixture was added a tetrahydrofuran (10 ml) solution of 4-pyridinecarboxyaldehyde(0.764 ml, 8.00 mmol) at -78C. The resulting mixture was stirred at the same temperature for 30 minutes. After the temperature of the reaction mixture was raised to room temperature, diethyl ether was added thereto. The resulting mixture was washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel chromatography. The fraction obtained from the hexane:ethyl acetate=7:3 eluate was concentrated under reduced pressure. The solid thus obtained was washed with diisopropyl ether and then collected by filtration to give the title compound (1.15 g, 5.20 mmol, 65%) as a white powder. 1H-NMR (400MHz, CDCl3) delta: 4.25 (1H,brs), 6.09 (1H,s), 6.89-7.05(2H,m), 7.14-7.23 (1H,m), 7.34 (2H,d, J=5.4Hz), 8.44(2H,d,J=5.4Hz).

According to the analysis of related databases, 399-94-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1640366; (2006); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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 399-94-0, Formula: C6H3BrF2

2-Bromo-3,6-difluorobenzaldehyde (C2.1) (0506) To a solution of 2-bromo-1,4-difluorobenzene (16 g, 83 mol) in 200 mL THF under N2 atmosphere at -78 C. was added LDA (54 mL, 108 mmol) dropwise. After stirring at -78 C. for 45 min, DMF (18.2 g, 249 mmol) was added. The mixture was stirred for another 2 h at -78 C. The reaction mixture was warmed up to 0 C., added 200 mL and sat. NH4Cl was added. The resulting mixture was extracted with EtOAc (200 mL×2). The combined organic layer was washed with brine (400 mL×1), dried over anhydrous Na2SO4, filtered and concentrated under vacuum to give crude product. The crude product was purified by column chromatography (silica, EtOAc/PE=1/30) to give the title compound (11 g, 60%) as a yellow solid. 1H NMR (500 MHz, CDCl3) delta ppm 7.57-7.34 (m, 2H), 10.20 (dd, 1H).

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-2,5-difluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Novartis AG; CHAN, Ho Man; GU, Xiang-Ju Justin; HUANG, Ying; LI, Ling; MI, Yuan; QI, Wei; SENDZIK, Martin; SUN, Yongfeng; WANG, Long; YU, Zhengtian; ZHANG, Hailong; ZHANG, Ji Yue (Jeff); ZHANG, Man; ZHANG, Qiong; ZHAO, Kehao; (134 pag.)US2016/176882; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 399-94-0, name is 1-Bromo-2,5-difluorobenzene, A new synthetic method of this compound is introduced below., Safety of 1-Bromo-2,5-difluorobenzene

THF (25 mL) was added to Magnesium metal (2.55g, 105 mmol), and then 2-bromo-1,4-difluorobenzene (19.70g, 100mmol) was addedslowly to prepare a Grignard reagent. To separately prepared THF (10mL)solution of diethyl oxalate (15.34g, 105mmol), Grignard reagent preparedearlier was added dropwise at -40 below. After completion of the addition, it was stirred for 1 hour at thereaction temperature of 0 . saturated aqueous solution of ammonium chlorideand water (200 mL) were added to the reaction solution, and extracted with ethyl acetate (200mL ×2). The organic layer was dried over magnesium sulfate, filtered, and thesolvent was evaporatedunder reduced pressure, and by distillation under reducedpressure, colorless liquid of 2- (2,5-difluorophenyl) -2- oxo-ethyl acetate(14.82g, yield: 62%)

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; SAGAMI CHEMICAL RESEARCH INSTITUTE; KAKEN PHARMACEUTICAL COMPANY LIMITED; KOBAYASHI, OSAMU; TAKATSUNA, REIKO; NIIKURA, NAOKO; MATSUKAWA, TOMOKO; NAKAMURA, SHINJI; HIRAI, KENJI; KOCHI, SHINICHIRO; KAWANISHI, NAOKI; YAMADA, OSAMU; (75 pag.)JP2016/56157; (2016); A;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 399-94-0, name is 1-Bromo-2,5-difluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 1-Bromo-2,5-difluorobenzene

Concentrated sulfuric acid (57 mL) was cooled inan ice bath, and 69% nitric acid (25.5 g, 279 mmol) was added dropwise over 25minutes to prepare a mixed acid. To this mixed acid, under ice-cooling, dichloroethane(125mL) solution of 2-bromo-1,4-difluoro-benzene (50g, 254mmol) was droppedslowly over a period of 1.5 hours. After completion of the dropwise addition,the reaction solution was further stirred for 2 hours at room temperature.After completion of the reaction, the reaction solution was added in portionsto ice-water (500 g), then extracted with ether (300mL × 2). The organic layerwas washed successively with water (300mL), saturated aqueous sodium hydrogencarbonate solution (300mL), saturated brine (300mL), and then dried overanhydrous magnesium sulfate, and the solvent was evaporated under reducedpressure. The resulting crude product was purified by silica gel chromatography(hexane: chloroform = 4/1) to give a pale yellow solid of 1-bromo-2,5-difluoro-4-nitrobenzene(56 g, yield: 93% ).

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 399-94-0.

Reference:
Patent; SAGAMI CHEMICAL RESEARCH INSTITUTE; KAKEN PHARMACEUTICAL COMPANY LIMITED; KOBAYASHI, OSAMU; TAKATSUNA, REIKO; NIIKURA, NAOKO; MATSUKAWA, TOMOKO; NAKAMURA, SHINJI; HIRAI, KENJI; KOCHI, SHINICHIRO; KAWANISHI, NAOKI; YAMADA, OSAMU; (75 pag.)JP2016/56157; (2016); A;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 399-94-0,Some common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, molecular formula is C6H3BrF2, 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 2-bromo-1,4-difluorobenzene (186 g) in THF (1.0 L) was added 2.0M isopropylmagnesium chloride solution in THF (482 mL) at -40C, and continuously stirred at 5C for 1 h. To the above reaction mixture was added a solution of tert-butyl 2-oxopyrrolidine-1-carboxylate (215.5 g) in THF (250 mL) dropwise, and continuously stirred at 10C for 2h. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to afford a crude product of the title compound (323.4 g), which was used in a next step without purification.

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-2,5-difluorobenzene, its application will become more common.

Reference:
Patent; Chia Tai Tianqing Pharmaceutical Group Co., Ltd.; Centaurus BioPharma Co., Ltd.; Lianyungang Runzhong Pharmaceutical Co., Ltd.; ZHU, Li; HU, Yuandong; WU, Wei; DAI, Liguang; DUAN, Xiaowei; YANG, Yanqing; SUN, Yinghui; HAN, Yongxin; PENG, Yong; KONG, Fansheng; LUO, Hong; YANG, Ling; XU, Hongjiang; GUO, Meng; ZHONG, Zhaobai; WANG, Shanchun; (80 pag.)EP3533796; (2019); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 399-94-0, name is 1-Bromo-2,5-difluorobenzene, A new synthetic method of this compound is introduced below., COA of Formula: C6H3BrF2

Under N2 protection, 2,5-difluorobromobenzene (15.05 g, 78 mmol) was dissolved in dry toluene (50 ml), cooledto -10C or lower in an ice salt bath, and a solution of isopropyl magnesium chloride/lithium chloride in tetrahydrofuran(66 ml, 1.3 mol/l) was added dropwise, followed by stirring at about -10C for 1 hour. 1D (10 g, 39 mmol) was dissolvedin dry tetrahydrofuran (100 ml), and added dropwise to the reaction solution while the temperature was maintained at-10C. When the addition was complete, the reaction was allowed to proceed at room temperature for 4 hours. Thetemperature was lowered to about -10C, and a saturated ammonium chloride solution (40 ml) was added dropwise,followed by stirring for 10 min. The pH was adjusted to 5 to 6 with a 3 mol/l hydrochloric acid solution, to allow settlingand partitioning. The aqueous phase was extracted with methyl t-butyl ether (50 ml32). The organic phases werecombined, washed with a saturated sodium chloride solution (30 ml32), dried by addition of anhydrous sodium sulfatethereto, filtered, concentrated, and separated by column chromatography (petroleum ether/ethyl acetate (v/v) = 50:1 to8:1), to obtain a light yellow solid 1E (10.1 g, yield 83.5%).MS m/z (ESI): 210.1 [M-99].

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; Sichuan Haisco Pharmaceutical Co., Ltd.; ZHANG, Chen; WANG, Jianmin; LI, Caihu; WEI, Yonggang; (64 pag.)EP3159344; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary