Category: 399-94-0

Electric Literature of 399-94-0, These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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.

Method B:To a solution of 1-bromo-2,5-difluorobenzene (42.2 g, 0.218 mol) in toluene (85 mL) at -10 to -5 C. was added iPrMgCl/LiCl solution (1.0 M in THF, 240 mL, 0.24 mol) dropwise over 1.5 h. The reaction solution was then aged for 30 min at -10 to -5 C.In a separate vessel, Weinreb amide 4 (28 g, 0.109 mol) was dissolved in THF (112 mL), cooled to 15 C. and then charged to the above Grignard solution over about 30 min, while the internal temperature was maintained at -10 to -5 C. The reaction mixture was then warmed to 20 C. over 1 h, and aged for additional 1 h at 20 C. for complete reaction. The reaction mixture was quenched with an aqueous HCl solution (32.5 g of concentrated hydrochloric acid in 110 mL of water) at 0 to 10 C. over 30 min. The organic phase was washed with 10% NaCl solution (200 mL×2). The organic phase was solvent switched to iPrOH (final volume about 270 mL) and water (380 mL) was added over 1 h at 20 C. Solids were filtered and washed with 40% iPrOH in water (60 mL×2). The wet cake was dried under vacuum at 45 C.1H-NMR (500 MHz, CDCl3): delta 7.56 (m, 1H), 7.25 (m, 1H); 7.15 (m, 1H), 5.67 (d, J=7.3 Hz, 1H), 5.24 (m, 1H), 2.91 (m, 1H), 2.68 (m, 1H), 2.00 (t, J=2.43, 1H), 1.45 (s, 9H). 13C-NMR (125 MHz, CDCl3): delta 159.03 (dd, J=245.5, 1.8 Hz), 157.4 (d, J=248.0 Hz), 124.6 (dd, J=15.4, 6.2 Hz), 122.2 (dd, J=24.6, 9.8 Hz), 118.4 (dd, J=27.1, 8.0 Hz), 117.6 (DD, J=25.2, 3.7 Hz), 80.4, 78.4, 72.1, 57.9 (d, J=7.5 Hz), 28.5, 22.3.

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

Reference:
Patent; Xu, Feng; Kim, Mary M.; Kohmura, Yoshinori; Sladicka, Tricia; Rosen, Jonathan D.; Zacuto, Michael J.; US2009/187028; (2009); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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. 399-94-0, name is 1-Bromo-2,5-difluorobenzene belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. HPLC of Formula: C6H3BrF2

2-bromo-l,4-difluorobenzene (1.5 eq.) was dissolved in 4 volumes of THF (based on weight of tert-butyl2-oxopyrrolidine-l-carboxylate) and cooled to about 5 Celsius. A solution of 2.0 M iPrMgCl in THF (1.4 eq.) was added over 2 hours to the mixture while maintaining a reaction temperature below 25 Celsius. The solution was allowed to cool to about 5 Celsius and stirred for 1 hour (GC analysis confirmed Grignard formation). A solution of tert-butyl 2-oxopyrrolidine-l-carboxylate (1.0 eq.) in 1 volume of THF was added over about 30 min while maintaining a reaction temperature below 25 Celsius. The reaction was stirred at about 5Celsius for 90 min (tert-butyl 2-oxopyrrolidine-l-carboxylate was confirmed to be less than 0.5 area % by HPLC). The reaction was quenched with 5 volumes of 2M aqueous HC1 while maintaining a reaction temperature below 45 Celsius. The reaction was then transferred to a reparatory funnel adding 10 volumes of heptane and removing the aqueous layer. The organic layer was washed with 4 volumes of saturated aqueous NaCl followed by addition of 2×1 volume of saturated aqueous NaCl. The organic layer was solvent-switched to heptane (<1% wt THF confirmed by GC) at a distillation temperature of 35-55 Celsius and distillation pressure of 100-200 mm Hg for 2x4 volumes of heptane being added with a minimum distillation volume of about 7 volumes. The mixture wasthen diluted to 10 volumes with heptane while heating to about 55 Celsius yielded a denser solid with the mixture being allowed to cool to room temperature overnight. The slurry was cooled to less than 5 Celsius and filtered through polypropylene filter cloth. The wet cake was washed with 2x2 volumes of heptane. The solids were dried under vacuum at 55 Celsius until the weight was constant, yielding tert-butyl (4-(2,5-difluorophe-nyl)-4-oxobutyl)-carbamate as a white solid at about 75% to 85% theoretical yield. The synthetic route of 399-94-0 has been constantly updated, and we look forward to future research findings. Reference:
Patent; Array BioPharma, Inc.; Arrigo, Alisha B.; Juengst, Derrick; Shah, Khalid; (70 pag.)US2016/137654; (2016); 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, Product Details of 399-94-0

To a solution of 2-bromo-1,4-difluorobenzene (1 g, 5.18 mmol) in THF (25 mL) was added LDA solution (2 M in THF, 2.9 mL, 5.8 mmol) dropwise at -78 C. After stirring for 1 h at -78 C., DMF (0.441 mL, 6.03 mmol) was added dropwise and the resulting reaction mixture was stirred at -78 C. for additional 30 min. The reaction was quenched by sat. NH4Cl solution (40 mL) carefully and the mixture was extracted with EtOAc (80 mL*2). The combined organic phase was washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 2-bromo-3,6-difluorobenzaldehyde as light brown solid (1.05 g, 92%, crude yield) which was used in next step without further purification.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2,5-difluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Merck Patent GmbH; SHERER, Brian A.; (167 pag.)US2016/75711; (2016); 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.

2-Bromo-l,4-difluorobenzene(53.6 g, 277.74 mmol) in THF cooled to -50C was added to isopropyl magnesium chloride (2M in THF)( 133mL, 266 mmol). The reaction mixture thus obtained was warmed to 0C and stirred for lh. The reaction mixture was cooled again to -50C. 4-chloro-N-methoxy-N-methylbutanamide (40 g, 241.52 mmol) in THF (200mL) was added dropwise to this reaction mixture with stirring and the stirring was continued at 0C for lh. The reaction mixture was quenched with saturated aqueous NH4C1 solution, extracted with ethylacetate. The organic layer collected was washed with water (500 mL) and then with brine solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford a crude liquid residue. The residue thus obtained was purified by column chromatography (using 60-120 silica gel and 5% EtOAc in Hexane as eluent) to afford 35 g of the title compound as a colourless liquid. 1H NMR (300MHz, CDC13) delta ppm 7.6-7.53(lH, m), 7.26-7.09(2H, m), 3.7(2H, t) 3.22- 3.14(2H, m), 2.28-2.16(2H, m).

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; 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

Application 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.

At -40C,Add 2.0 M isopropyl chloride to a solution of 2-bromo-1,4-difluorobenzene (186 g) in THF (1.0 L)Magnesium in THF (482 mL),And continue stirring at 5 C for 1 h.At -40C,A solution of tert-butyl 2-oxopyrrolidine-1-carboxylate (215.5 g) in THF (250 mL) was added dropwise to the above reaction mixture.And continue stirring at 10 C for 2 h.The reaction mixture was quenched with saturated ammonium chloride solution,Extract with ethyl acetate,Dry with anhydrous sodium sulfatefilter,And concentrate the filtrate under reduced pressure,The crude title compound was obtained (323.4 g),It is used directly in the 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; Zhengda Tianqing Pharmaceutical Group Co., Ltd.; Beijing Sai Lintai Pharmaceutical Co., Ltd.; Lianyungang Runzhong Pharmaceutical Co., Ltd.; Zhu Li; Hu Yuandong; Dai Liguang; Yang Yanqing; Duan Xiaowei; Yang Zhao; Wu Wei; Sun Yinghui; Han Yongxin; Peng Yong; Luo Huiyan; Luo Hong; Yang Ling; Xu Hongjiang; Guo Meng; Zhong Zhaobo; Wang Shanchun; (102 pag.)CN108003161; (2018); A;,
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., HPLC of Formula: C6H3BrF2

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

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.

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, HPLC 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. SDS of cas: 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

Related Products of 399-94-0, These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, 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.

A solution of tert-butyl pyrrolidine- 1-carboxylate (20 g, 116.8 mmol) and (- )sparteine (32.9, 140 mmol) in MTBE (360 mL) was cooled to -78 0C, and sec-BuLi (10OmL, 140 mmol, 1.4 M in cyclohexane) was introduced drop-wise via cannula, keeping the internal temperature under -70 0C. The resulting solution was stirred for 3 hours at -78 0C, followed by addition of a solution of ZnCl2 (93.4 mL, 93.4 mmol, IM in Et2O) drop-wise with rapid stirring, keeping the internal temperature below -65 0C. The resulting light suspension was stirred at -78 0C for 30 minutes and then warmed to ambient temperature. The resulting mixture was charged with 2-bromo-l,4-difluorobenzene (14.5 mL, 128 mmol), followed by Pd(OAc)2 (1.31 g, 5.8mmol) and ^-Bu3P-HBF4 (2.03 g, 7.0 mmol) in one portion. After stirring overnight at ambient temperature, 10.5 mL Of NH4OH solution was added and the reaction was stirred for another hour. The resulting slurry was filtered through CELITE and washed with Et2O (1 L). The filtrate was washed with HCl (0.5 L, IM aq.) and brine. The organic layer was filtered and concentrated, and the crude product was purified by silica column chromatography, eluting with 5-10% EtO Ac/hex anes to give product (R)-tert-butyl 2- (2,5-difluorophenyl)pyrrolidine- 1-carboxylate as yellow oil (23.9 g, 72% yield).

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

Reference:
Patent; ARRAY BIOPHARMA INC.; ANDREWS, Steven, W.; HAAS, Julia; JIANG, Yutong; ZHANG, Gan; WO2010/33941; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary