Category: 64248-56-2

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 64248-56-2 as follows. COA of Formula: C6H3BrF2

Preparation 105 Preparation of tert-Butyl 9-(2,6-difluorophenyl)-1,4,5,6-tetrahydroazepino-[4,5-b]indole-3(2H)-carboxylate. A solution of 1-bromo-2,6-difluorobenzene (0.28 g, 1.5 mmol) in dioxane (12 mL) was added to a flask charged with 3-(tert-butyloxycarbonyl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.50 g, 1.2 mmol), Pd2(dba)3 (0.11 g, 0.12 mmol) and potassium phosphate(0.59 g, 2.8 mmol). Next, trimethylphosphite (0.045 mL, 0.38 mmol) was added and the mixture was heated to 95 C. After 28.5 h, the reaction was cooled to rt, diluted with H2O, and extracted with EtOAc (3*50 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40M, SIM) with heptane/EtOAc (4:1) to give 0.38 g (80%) of a pale yellow solid: mp 225.5-226 C.; % water (KF): 0.10; melt solvate: 1.46% CH2Cl2; 0.19% EtOAc; Anal. Calcd for C23H24F2N2O2-0.10% H2O·1.46% CH2Cl2·0.19% EtOAc: C, 68.34; H, 6.19; N, 6.91; found: C, 68.34; H, 6.19; N, 6.81.

According to the analysis of related databases, 64248-56-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Frank, Kristine E.; Acker, Brad A.; Ennis, Michael D.; Fisher, Jed F.; Fu, Jian-min; Jacobsen, Eric Jon; McWhorter JR., William W.; Morris, Jeanette K.; Rogier, Donald Joseph; US2002/77318; (2002); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 64248-56-2, A common heterocyclic compound, 64248-56-2, name is 2-Bromo-1,3-difluorobenzene, molecular formula is C6H3BrF2, 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.

To a stirred solution of 2-bromo-l,3-diflurobenzene (CAS 64248-56-2, 10.0 g, 51.8 mmol) in H2SO4 (30 mL) at 0 C under nitrogen atmosphere was added HNO3 (65%, 25 mL) in dropwise. The resulting mixture was warmed to room temperature and stirred for 1 hour. After that, the reaction mixture was poured onto ice and vigorously stirred for 5 minutes. The resulting suspension was extracted with CH2CI2 (4 x 125 mL), washed with brine (200 mL), dried over Na2S04 and concentrated in vacuo to get compound XIa (crude). The obtained crude product was taken for the next step without any further purification. Yield: 9.00 g, 72.99%. -1H NMR (400 MHz, DMSO-d6): 8.34- 8.29 (m, 1H), 7.56 – 7.51 (m, 1H).

The synthetic route of 64248-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BUGWORKS RESEARCH INDIA PVT LTD; PEER MOHAMED, Shahul Hameed; BHARATHAM, Nagakumar; KATAGIHALLIMATH, Nainesh; SHARMA, Sreevalli; NANDISHAIAH, Radha; RAMACHANDRAN, Vasanthi; VENKATARAMAN, Balasubramanian; (221 pag.)WO2018/225097; (2018); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

64248-56-2, name is 2-Bromo-1,3-difluorobenzene, belongs to bromides-buliding-blocks compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: 2-Bromo-1,3-difluorobenzene

Preparation of 2-bromo-1,3-difluoro-4-nitrobenzene [(35), G= NO2; L’ = Br; R3,R6 = F; R4,R5 = H]; To a stirred, ice-cooled, solution of 1,3-difluoro-2-bromobenzene (1.74 g, 9.0 mmol) in 96% sulphuric acid (2 mL), a mixture of 96% sulphuric acid (0.6 mL) and fuming nitric acid (0.6 mL) was slowly added, keeping the temperature below 55 0C. After addition, the reaction mixture was stirred at room temperature for 2 h, then poured onto ice. The precipitate was filtered, washed with water and dried. The title compound was obtained as a yellowish solid (1.7 g, 80%).HPLC (254 nm): Rt: 6.26 min. 1H-NMR (401 MHz, DMSO-d6) delta = 8.1 (m, 1 H) 7.1 (m, 1 H).

The synthetic route of 64248-56-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NERVIANO MEDICAL SCIENCES S.R.L.; PULICI, Maurizio; ZUCCOTTO, Fabio; BADARI, Alessandra; NUVOLONI, Stefano; CERVI, Giovanni; TRAQUANDI, Gabriella; BIONDARO, Sonia; TRIFIRO’, Paolo; MARCHIONNI, Chiara; MODUGNO, Michele; WO2010/10154; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 64248-56-2, 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. 64248-56-2 name is 2-Bromo-1,3-difluorobenzene, 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.

A mixture of 2, 6-difluorobromobenzene (125.5 g, 650 mmol) in 98% sulphuric acid (250 ml) was cooled in an ice-water bath and then treated with a 1: 1 mixture of 98% sulphuric acid and fuming nitric acid (100 ml) added at such a rate that the internal temperature never exceeded 35C. Once addition was complete the reaction was stirred at ambient temperature for 3 h then poured onto ice. This mixture was diluted with water (final volume 5 1), the resulting solid collected by filtration, washed with water, then dried under vacuum over phosphorus pentoxide, to afford 2-bromo-1, 3-difluoro-4-nitrobenzene as a cream-coloured solid (145 g, 94%) : 1H NMR (360 MHz, CDCl3) 8 7.10-7. 15 (1H, m), 8.09-8. 16 (1H, m).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Bromo-1,3-difluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME LIMITED; WO2003/93272; (2003); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 64248-56-2, A common heterocyclic compound, 64248-56-2, name is 2-Bromo-1,3-difluorobenzene, molecular formula is C6H3BrF2, 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.

Example A-22 4-(2,6-Difluoro-phenyl)-1H-indole To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (11.34 g, 46.6 mmol), and 1-bromo-2,6-difluorobenzene (9 g, 46.6 mmol) in 1,2-dimethoxyethane (204 mL) were added Palladium catalyst Pd(PPh3)4 (1.62 g, 1.4 mmol) and the freshly prepared sodium carbonate solution (15.19 g in 66 mL of water). The system was degassed and then charged with nitrogen. The degas procedure was repeated for three times. The mixture was stirred under nitrogen at 110 C. oil bath for overnight. TLC showed the completion of the coupling reaction. The mixture was cooled to room temperature, diluted with ethyl acetate, and separated from water layer. The ethyl acetate solution was washed with brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was purified by a silica gel column to give 9.77 g (91%) of 4-(2,6-difluoro-phenyl)-1H-indole.

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; Sugen, Inc.; US2003/69297; (2003); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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 64248-56-2 as follows. Recommanded Product: 2-Bromo-1,3-difluorobenzene

Preparation 105 Preparation of tert-Butyl 9-(2,6-difluorophenyl)-1,4,5,6-tetrahydroazepino-[4,5-b]indole-3(2H)-carboxylate. A solution of 1-bromo-2,6-difluorobenzene (0.28 g, 1.5 mmol) in dioxane (12 mL) was added to a flask charged with 3-(tert-butyloxycarbonyl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.50 g, 1.2 mmol), Pd2(dba)3 (0.11 g, 0.12 mmol) and potassium phosphate(0.59 g, 2.8 mmol). Next, trimethylphosphite (0.045 mL, 0.38 mmol) was added and the mixture was heated to 95 C. After 28.5 h, the reaction was cooled to rt, diluted with H2O, and extracted with EtOAc (3*50 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40M, SIM) with heptane/EtOAc (4:1) to give 0.38 g (80%) of a pale yellow solid: mp 225.5-226 C.; % water (KF): 0.10; melt solvate: 1.46% CH2Cl2; 0.19% EtOAc; Anal. Calcd for C23H24F2N2O2-0.10% H2O·1.46% CH2Cl2·0.19% EtOAc: C, 68.34; H, 6.19; N, 6.91; found: C, 68.34; H, 6.19; N, 6.81.

According to the analysis of related databases, 64248-56-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Frank, Kristine E.; Acker, Brad A.; Ennis, Michael D.; Fisher, Jed F.; Fu, Jian-min; Jacobsen, Eric Jon; McWhorter JR., William W.; Morris, Jeanette K.; Rogier, Donald Joseph; US2002/77318; (2002); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 64248-56-2, name is 2-Bromo-1,3-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. Computed Properties of C6H3BrF2

A solution of 2-bromo-1,3-difluorobenzene (25.0 g, 130 mmol) in concentrated H2SO4 (52 mL, 98%) was vigorously stirred at room temperature. Then, concentrated nitric acid (9 mL, 70%) was added dropwise to the solution, and the internal temperature was maintained to be lower than 55C. After the addition, the mixture was further stirred for 30 minutes, and poured on ice. CH2Cl2 (200 mL x 2) was added to the mixture for extraction of the desired compound. The combined organic layer was washed with saturated Na2CO3 and brine, dried over Na2SO4, and concentrated to give 2-bromo-1,3-difluoro-4-nitrobenzene as yellow solid (23.0 g, yield 74%). 1H-NMR Spectrum (300MHz, CDCl3):delta (ppm): 7.10-7.16 (m, 1H), 8.09-8.16 (m, 1H)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 64248-56-2, its application will become more common.

Reference:
Patent; Juntendo Educational Foundation; HIRAMATSU Keiichi; MORIMOTO Yuh; BABA Tadashi; HAYAKAWA Isao; (76 pag.)EP2987787; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary