Author: Jessica.F

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 203302-95-8 as follows. Recommanded Product: 203302-95-8

Intermediate H5,7-difluoro-quinoline-6-carbaldehyde 2 1 DnM”BFuLi i ii intermediate H 5,7-difluoro-phenylamine (10.0 g, 77.5 mmol) was dissolved in DMF (100 ml_). NBS (13.9 g, 78.0 mmol) was then added portionwise at room temperature. After stirring overnight at room temperature, the reaction mixture was diluted with Et2O and washed with brine. The separated organic phase was dried (Na2SO4) and concentrated to give an oil which is purified by column chromatography to give 4-bromo-3,5-difluoro-phenylamine (i) (12.9 g, 80.2%)A mixture of 4-bromo-3,5-difluoro-phenylamine (i) (6.0 g, 28.8 mmole), 1.82 g ferrous sulfate, 8.6 ml. glycerol, 1.79 ml. nitrobenzene , and 5.0 ml. concentrated sulfuric acid was heated gently. After the first vigorous reaction, the mixture was boiled for five hours. Nitrobenzene was removed by distillation in vacuo. The aqueous solution was acidified with glacial acetic acid, and dark brown precipitate separated, which was purified by flash chromatography (silica gel, petroleum/ethyl acetate= 12/1 ) to give 6-bromo-5,7-difluoroquinoline (ii) as a white solid (3.5 g, 49.8%).To a solution of 6-bromo-5,7-difluoroquinoline (ii) (250 g, 1.02 mol) in anhydrous THF (2200 ml.) at -780C, was added a solution of n-BuLi in hexane ( 2.5 M, 408 ml ,1.02 mol) dropwis. The resulting mixture was stirred for additional 30 min at -780C. Then, a solution of DMF (79 ml_, 1.02 mol) in anhydrous THF (200 ml.) was added while the temperature was kept lower than -700C, and the mixture was stirred at the same temperature for 30 mins. The reaction mixture was warmed slowly to room temperature and diluted with aqueous saturated solution of NH4CI (1000 ml.) and water (800 ml_). The mixture was extracted with ethyl acetate twice, the combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated to give brown oil, which was purified by column chromatography on silica gel eluted with petroleum and ethyl acetate (10:1 ) to give 5,7-difluoro-quinoline-6- carbaldehyde (intemediate H) as a yellow soild (100 g, 50%). 1H NMR (DMSO, 300MH) delta(ppm): 10.38(s, 1 H), 9.10~9.12(m, 1 H), 8.62~8.66(m,1 H),7.68~7.78(m,2H)

According to the analysis of related databases, 203302-95-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; FU, Xingnian; HE, Feng; LI, Yue; LIU, Lei; MI, Yuan; XU, Yao-chang; XUN, Guoliang; YU, Zhengtian; ZHANG, Ji Yue (Jeff); DAI, Miao; WO2011/18454; (2011); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 38573-88-5, name is 1-Bromo-2,3-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 38573-88-5, Recommanded Product: 1-Bromo-2,3-difluorobenzene

Example A-26 4-(2,3-Difluoro-phenyl)-1H-indole To a mixture of 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole (3.78 g, 15.5 mmol), and 1-bromo-2,3-difluorobenzene (3 g, 15.5 mmol) in THF (55 mL) were added Palladium catalyst Pd(PPh3)4 (0.54 g, 0.47 mmol) and the freshly prepared sodium hydroxide solution (1.865 g, 47 mmol in 22 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 75° 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 2.92 g (82percent) of 4-(2,3-difluoro-phenyl)-1H-indole.

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

Reference:
Patent; Sugen, Inc.; US2003/69297; (2003); 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. 52548-00-2, name is 1-Bromo-4-fluoro-2,3-dimethylbenzene belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. Formula: C8H8BrF

To a 250 ml-round bottle flask equipped with magnetic stir bar were added 1- Boc-piperizine (2.5 g, 13.42 mmol), 1-bromo-4-fluoro-2,3-dimethylbenzene (3.27 g, 16.11 mmol), Cs2CO3 (13.12 g, 40.3 mmol), and RuPhos Pd G2 (1.043 g, 1.342 mmol). To the mixture was charged dioxane (67.1 ml) at RT under N2. The mixture was stirred at RT while flushed with N2 for about 5 min and then warmed up to 90 C. The mixture was stirred at 90 C overnight. The mixture was cooled to RT, and partitioned between EtOAc and water (100 ml x 50 ml). The aqueous was extracted with EtOAc for three times (100 ml x 3). Organic phases were combined and washed with sat. NaCl, separated and dried over Na2SO4, filtered, concentrated, and followed by normal phase purfication (Isco system, 120 g Isco, RediSep gold column, 0-100% EtOAc / hexane as eluting solvent) to afford the title compound as a solid. LCMS m/z (M+H): 309.67

The synthetic route of 52548-00-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; CLAUSEN, Dane; CHEN, Ping; FRADERA, Xavier; GUO, Liangqin; HAN, Yongxin; HE, Shuwen; HUANG, Xianhai; KOZLOWSKI, Joseph; LI, Guoqing; MARTINOT, Theodore, A.; PASTERNAK, Alexander; VERRAS, Andreas; XIAO, Li; YU, Wensheng; ZHANG, Rui; (267 pag.)WO2020/112581; (2020); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 59734-92-8,Some common heterocyclic compound, 59734-92-8, name is 1-Bromo-2-cyclohexylbenzene, molecular formula is C12H15Br, 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 CuI (19 mg, 0.10 mmol) and NaI (0.6 g, 4.0 mmol) in pentanol (3 niL) was added (18 mg, 0.2 mmol) and l-bromo-2- cyclohexylbenzene (0.48 g, 2.0 mmol). The mixture was purged for 5 min with argon and heated overnight at reflux. The resulting mixture was purified by silica gel chromatography using hexanes to afford the title compound as clear oil (0.51 g, 90%).[0132] 1H NMR (500 MHz, CDCl3): delta 1.21-1.30 (m, IH), 1.33-1.53 (m, 4H), 1.76-1.90 (m, 5H), 2.77 (tt, J = 11.7, 3.1 Hz, IH), 6.86 (td, J = 7.7, 1.6 Hz, IH), 7.20 (dd, J= 7.8, 1.6 Hz, IH), 7.27 (q, J = 7.5 Hz, IH), 7.81 (d, J = 7.9 Hz, IH)

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-cyclohexylbenzene, its application will become more common.

Reference:
Patent; TARGEGEN INC.; WO2009/55674; (2009); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 201138-91-2,Some common heterocyclic compound, 201138-91-2, name is 4,6-Dibromodibenzo[b,d]furan, molecular formula is C12H6Br2O, 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 an argon atmosphere, to a 1,000 ml Erlenmeyer flask, 4,6-dibromodibenzofuran (16.3 g, 50 mmol), phenylboronic acid (6.71 g, 55 mmol), K2CO3 (20.7 g, 150 mmol), Pd(PPh3)4(2.89 g, 2.5 mmol), 500 ml of a mixture solution of toluene/EtOH/H2O (4/2/1) were added in order, followed by heating and refluxing at a temperature of about 80 C. for about 5 hours. Then, the reaction mixture was cooled to room temperature, and toluene was added thereto. An aqueous layer was removed, and an organic layer was washed with a saline solution and dried with MgSO4. MgSO4 was filtered and separated, and an organic layer was concentrated. The crude product thus obtained was separated by silica gel column chromatography (using a mixture solvent of hexane/toluene) and recrystallized to obtain Intermediate A as a white solid (12.1 g, yield 75%). The structure of the product was identified using FAB-MS (m/z=323).

The synthetic route of 201138-91-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Samsung Display Co., Ltd.; UNO, Takuya; (209 pag.)US2019/165285; (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. 2550-36-9, name is (Bromomethyl)cyclohexane, This compound has unique chemical properties. The synthetic route is as follows., Formula: C7H13Br

[0307] A four-necked reactor equipped with a thermometer was charged with 3.00 g (18.2 mmol) of 2-hydrazinobenzothiazole and 30 ml of DMF under a nitrogen stream to prepare a homogeneous solution. After the addition of 7.55 g (54.6 mmol) of potassium carbonate and 3.86 g (21.8 mmol) of (bromomethyl)cyclohexane to the solution, the mixture was stirred at 80C for 9 hours. After completion of the reaction, the reaction mixture was cooled to 20C, added to 300 ml of water, and extracted with 500 ml of ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a yellow solid. The yellow solid was purified by silica gel column chromatography (n-hexane:ethyl acetate=85:15 (volume ratio)) to obtain 2.36 g of an intermediate S as a white solid (yield: 49.7%). [0308] The structure of the target product was identified by 1H-NMR. [0309] 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 7.58 (d, 1H, J=8.0 Hz), 7.51 (d, 1H, J=8.1 Hz), 7.26 (dd, 1H, J=7.0 Hz, 8.1 Hz), 7.04 (dd, 1H, J=7.0 Hz, 8.0 Hz), 4.24 (s, 2H), 3.59 (d, 2H, J=7.4 Hz), 1.84-1.92 (m, 1H), 1.67-1.77 (m, 5H), 1.16-1.29 (m, 3H), 1.02-1.13 (m, 2H).

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 2550-36-9.

Reference:
Patent; Zeon Corporation; SAKAMOTO Kei; OKUYAMA Kumi; EP2703385; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 445-02-3,Some common heterocyclic compound, 445-02-3, name is 4-Bromo-2-(trifluoromethyl)aniline, molecular formula is C7H5BrF3N, 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.

Isopentyl nitrite (0. 67ML) was added dropwise to a solution of 4-bromo-2- (trifluoromethyl) aniline (1.2g) and dimethyl sulfide (0. 45ML) in acetonitrile (12ML). The reaction was slowly heated to reflux and then refluxed until gas evolution ceased. The volatiles were evaporated, the residue absorbed onto silica and the product eluted off with isohexane. YIELD 0. 8G. 1H NMR DMSO-d6: 8 7.59 (dd, 2H), 7.23 (d, 1H), 2.51 (s, 3H)

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-(trifluoromethyl)aniline, its application will become more common.

Reference:
Patent; ASTRAZENECA AB; WO2004/89885; (2004); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 7745-91-7, 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. 7745-91-7 name is 3-Bromo-4-methylaniline, 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.

Method 8; JV-(3-Bromo-4-methylphenylV3-(trifluoromethyl>)benzaniide3-(Trifluoromethyl)benzoyl chloride (0.78 ml, 5.2 mmol) was added to a stirring solution of 3-bromo-4-methylaniline (0.74 g, 4.0 mmol) and triethylamine (1.65 ml, 12 mmol) in 15 ml DCM. The mixture was stirred at 25 0C for 4 h. The reaction mixture was washed with 1 N HCl, 10 % NaOH, water and brine. The combined organics were dried and concentrated under reduced pressure. The resulting residue was used without further purification; m/z 359

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 3-Bromo-4-methylaniline, and friends who are interested can also refer to it.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; WO2006/79791; (2006); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 7617-93-8, 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. 7617-93-8, name is 2-Bromo-1,4-bis(trifluoromethyl)benzene, This compound has unique chemical properties. The synthetic route is as follows.

Reference Example 30 1-[2,5-bis(trifluoromethyl)phenyl]pyrrolidin-3-ol; A solution of 2,5-bis(trifluoromethyl)phenyl bromide (4.45 g), 3-hydroxypyrrolidine (1.2 g), palladium(II) acetate (0.16 g), (+/-)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.87 g) and cesium carbonate (13.6 g) in toluene (74 mL) was stirred under an argon gas atmosphere at 80C for 16 hr. The reaction mixture was allowed to cool to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate 90:10 – 75:25) to give the title compound (3.79 g, yield 91%) as an orange oil. 1H-NMR (300 MHz, CDCl3)delta:1.72 (d, J = 4.9 Hz, 1 H), 1.95 – 2.10 (m, 1 H), 2.10 – 2.24 (m, 1 H), 3.21 – 3.43 (m, 2 H), 3.60 – 3.78 (m, 2 H), 4.48 – 4.65 (m, 1 H), 7.01 – 7.16 (m, 1 H), 7.16 – 7.23 (m, 1 H), 7.63 – 7.74 (m, 1 H).

The chemical industry reduces the impact on the environment during synthesis 2-Bromo-1,4-bis(trifluoromethyl)benzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; Takeda Pharmaceutical Company Limited; EP2295406; (2011); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 1435-51-4,Some common heterocyclic compound, 1435-51-4, name is 1,3-Dibromo-5-fluorobenzene, molecular formula is C6H3Br2F, 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.

Preparation 4.; (4- (3-bromo-5-fluoro-phenyl)-cyclohex-3-enyl)-dimethyl-amine (enantiomer 2); Dissolve 1, 3-dibromo-5-fluoro-benzene (19.8 g, 77.90 mmol) in dry diethyl ether (300 mL) and cool to-60C. Add 1.6M n-BuLi in hexanes (50.9 mL, 81.44 mmol) dropwise over 15 min. and stir an additional 15 min. Add a pre-cooled (-60C) solution of 4-dimethylamino-cyclohexanone (10.0 g, 70.8 mmol) in diethyl ether (200 mL) dropwise over 30 min. Stir at-60C to-20C for 2 hr. , then warm to ambient temperature and stir for 1 hr. Quench the reaction with water (200 mL) and extract with ethyl acetate (3 x 200 mL). Dry over sodium sulfate, filter and concentrate. Purify the residue by flash chromatography (15% 2M NH3/MeOH in DCM) to obtain 1- (3-Bromo-5- fluoro-phenyl) -4-dimethylamino-cyclohexanol as a white foam (14. 5 g, 64.8%). MS (ES) m/z = 316 (M-H)-, 318 (M+H) +, 1H NMR (CDC13) : 8 7.41 (d, 1H, J= 2 Hz), 7.15 (m, 2H), 2.3 (m, 8H), 1.78 (m, 8H). Combine 1- (3-bromo-5-fluoro-phenyl)-4-dimethylamino-cyclohexanol (14.5 g, 45.9 mmol), p-TsOH (21.8 g, 114.6 mmol) and toluene (200 mL) and heat to reflux for 3 hr. Cool to ambient temperature and partition between ethyl acetate (500 mL) and 1M NaOH solution (250 mL). Wash the organic layer with 1M NaOH solution (200 mL) and saturated aqueous NaCl (200 mL), dry over sodium sulfate, filter and concentrate. Purify the residue by chromatography (silica gel, 10% 2M NH3/MeOH in DCM) to obtain (4- (3- bromo-5-fluoro-phenyl) -cyclohex-3-enyl) -dimethyl-amine (10.8 g, 79%): MS (ES) m/z= 298 (M-H)’, 300 (M+H) ; 1H NMR (CDC13) : 8 7.25 (d, 1H, J= 2 Hz), 7.02 (dd, 1H, J= 8 Hz, J= 2 Hz), 6.9 (dd, 1H, J= 8 Hz, J= 2 Hz), 6.04 (m, 1H), 2. 38 (m, 4H), 2.27 (s, 6H), 2.09 (m, 2H), 1.48 (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 1,3-Dibromo-5-fluorobenzene, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; WO2005/61439; (2005); A1;,
Bromide – Wikipedia,
bromide – Wiktionary