Category: 627526-90-3

627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, 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. category: bromides-buliding-blocks

(A) To a solution of 3-bromo-5-fluorobenzaldehyde (15 g, 73.89 mmol, 1 eq) in DCM (150 ml) was addedDAST (39 ml, 295.5 mmol 4 eq) dropwise at -78C and the mixture was stirred at RT for 16 h. Aftercompletion of the reaction, the mixture was poured into ice-cold water and basified with sat. NaHCO3solution. The mixture was then extracted with DCM (3 x 200 ml), washed with water (200 ml) and brine (200 ml), dried (Na2SQ4), and concentrated in vacuum to give the crude product, which was purified by flash chromatography to afford 1 -bromo-3-(difluoromethyl)-5-fluorobenzene (10 g, 60%).

The synthetic route of 627526-90-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; GRUeNENTHAL GMBH; SCHUNK, Stefan; REICH, Melanie; JAKOB, Florian; DAMANN, Nils; HAURAND, Michael; KLESS, Achim; ROGERS, Marc; SUTTON, Kathy; WO2015/158427; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 627526-90-3, 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. 627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows.

steps 3-5; – /?-Methoxybenzyl alcohol (36.8 g, 266.7 mmol) was added slowly to a mixture of potassium t-butoxide (28.7 g, 255.5 mol) and THF (250 mL). After stirring for about 15 min, 30 (50.O g, 222.2 mmol) was added and the reaction mixture heated to about 65 C. After stirring at 65 C for 2 h, the reaction is analyzed by HPLC. After cooling to RT, a mixture of saturated NaHCO3 solution (150 mL) and water (150 mL) was added. Toluene (300 mL) was added, the organic phase separated and washed with a mixture of saturated NaHCO3 solution (75 mL) and water (75 mL). Polish filtration and concentration in vacuo provided 83.9 g of crude 32 as an oil which is used without further purification.To a solution of crude 32 in NMP (180 ml) was added potassium ferrocyanide(31.1 g, 84.44 mmol) and Na2CO3 (23.55 g, 222.2 mmol). The resulting slurry was degassed thoroughly via repeated evacuation and purging with nitrogen. The slurry was heated to about 100 C and a solution of Pd(OAc)2 (150 mg, 0.67 mmol) and DPPF (505 mg, 0.91 mmol) in degassed NMP (20 mL) added. The mixture was heated to ca. 130 C for about 3 h. HPLC analysis indicated ca. 5% starting material remained. Additional Pd(OAc)2 (50 mg, 0.22 mmol) is added and heating at 130 C was continued for 1.5 h when HPLC analysis showed complete conversion.After cooling toluene (400 mL) and saturated sodium sulfite solution (10 mL) are added and mixture heated at ca. 40 C for about 1 h. Solka-floc (10 g) was added and the mixture was filtered through a bed of Solka-floc and the cake was washed with toluene {ca. 100 mL total). The filtrate was washed successively with dilute sodium sulfite solution (1 x 400 mL) and water (2 x 200 mL). The combined aqueous phases are extracted with toluene (1 x 100 mL) and the toluene back extracted with water (2 x 50 mL). The combined organic phases are polish filtered, and concentrated in vacuo to obtain 70.4 g of 34 as a dark-colored oil (70.4 g) which was used in the next step without further purification.To the solution of crude 36 in toluene (190 mL) and anisole (65 mL) is added TFA (25.3 g, 222.2 mmol). The reaction was heated to ca. 65 C and stirred for about 2 h until the reaction was complete by HPLC. The mixture was distilled in vacuo to remove most of the TFA. After cooling, the mixture is extracted twice with ca. 10% Na2CO3 solution (300 mL then 150 mL). The combined aqueous phases were acidified to a pH of 5.5 with con HCl and extracted with EtOAc (2 x 200 mL). The combined organic phases were washed with water (1 x 150 ml), polish filtered and the solvent replaced with toluene by vacuum distillation. The solution was concentrated to ca. 200 mL, then heptane (200 mL) was slowly added and the mixture heated to 80 C. The mixture was cooled to RT, aged overnight, filtered, and washed with 50% heptane in toluene {ca. 30 mL). The isolated product was dried in vacuo at ca. 60 C to afford 29.0 g (77.2% yield over 3 steps)of 36.

The chemical industry reduces the impact on the environment during synthesis 1-Bromo-3-(difluoromethyl)-5-fluorobenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; F. HOFFMANN-LA ROCHE AG; WO2008/145563; (2008); A2;,
Bromide – Wikipedia,
bromide – Wiktionary

Adding a certain compound to certain chemical reactions, such as: 627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, 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 627526-90-3, HPLC of Formula: C7H4BrF3

A mixture of 1-bromo-3-(difluoromethyl)-5-fluoro-benzene (ig, 4.44 mmol) and 1- cyclopropylpiperazine (2.80 g, 22.22 mmol) was microwaved at 200 C for 1 h. Pumped down solvent and purified the crude mixture by ISCO purification (40g silica; 0 % to 5% to 30% of MeOH in DCM) to provide 1-[3-bromo-5-(difluoromethyl)phenyl]piperazine (920 mg, 89%). ?H NMR (300 MHz, CD3OD) oe 7.20 (s, 1H), 7.09 (s, 1H), 7.05 (d, J = 1.0 Hz, 1H), 6.66 (t, J = 56.1 Hz, 1H), 3.20 (dd, J = 6.2, 4.0 Hz, 4H), 2.98 (dd, J = 6.2, 4.1 Hz, 4H) ppm. ESI-MS m/z calc. 290.02, found 291.19 (M+1)+; Retention time: 0.63 minutes.

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-3-(difluoromethyl)-5-fluorobenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; DAVIES, Robert, J.; CAO, Jingrong; COCKERILL, Meghan, Elise; COLLIER, Philip, Noel; DENINNO, Michael, Paul; DOYLE, Elisabeth; FRANTZ, James, Daniel; GAO, Huai; GOLDMAN, Brian, Anthony; GREY, Ronald, Lee; GRILLOT, Anne-laure; GU, Wenxin; HENDERSON, James, A.; IRARRAZAVAL, Raul Eduardo, Krauss; KOLPAK, Adrianne, Lynn; LIAO, Yusheng; MAGAVI, Sanjay Shivayogi; MALTAIS, Francois; MESSERSMITH, David; PIERCE, Albert, Charles; PEROLA, Emanuele; RYU, Elizabeth Jin-Sun; SYKEN, Joshua; WANG, Jian; (706 pag.)WO2016/197009; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, 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. Computed Properties of C7H4BrF3

A solution of 64c (41.6 g, 0.182 mol), Pd[P(Ph)3]4(0) (15 g, 13 mmol), and zinc cyanide (12.82 g, 0.109 mol) in dry DMF (400 mL) under nitrogen was heated to 80 C. for 5.5 h. The reaction mixture was cooled to RT, the yellow solid filtered and the filtrate added to water (500 mL). The filtrate was thrice extracted with Et2O and the combined extracts washed twice with water, dried (MgSO4), filtered and evaporated at 30 C. The crude was purified by SiO2 chromatography eluting with a hexane/EtOAc gradient (100:0 to 95:5 to 90:10) to provide 26.3 g of 66 as a colorless oil which partially crystallizes

The synthetic route of 627526-90-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Roche Palo Alto LLC; US2005/239881; (2005); 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. 627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C7H4BrF3

(B) To a solution of 1-bromo-3-(difluoromethyl)-5-fluorobenzene (8.6 g, 38.56 mmol, I eq) and DIPEA(13.44 ml, 77.12 mmol, 2 eq) in 1,4-dioxane (150 ml) was added PMB-SH (5.89 ml, 42.42 mmol, 1.1 eq).The mixture was degassed for 10 mm, and Xantphos (1.56 g, 2.69 mmol, 0.07 eq), followed by Pd2(dba)3 (1.0 g, 1.15 mmol, 0.03 eq) were added. The mixture was again degassed for 10 mm. The resulting RM was heated to 90 C and stirred for 2 h under Ar. The RM was filtered through celite and the filtrate concentrated to yield the crude product, which upon flash chromatography afforded 1 -bromo-3-(difluoro-methyl)-5-fluorobenzene (10 g, 87%).

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 627526-90-3.

Reference:
Patent; GRUeNENTHAL GMBH; SCHUNK, Stefan; REICH, Melanie; JAKOB, Florian; DAMANN, Nils; HAURAND, Michael; KLESS, Achim; ROGERS, Marc; SUTTON, Kathy; WO2015/158427; (2015); 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. 627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, A new synthetic method of this compound is introduced below., Computed Properties of C7H4BrF3

To a solution of magnesium (165 mg, 6.81 mmol) and lithium chloride (144 mg, 3.40 mmol) in THF (6.0 mL) was added DIBAL-H (27.2 muL, 0.027 mmol). After 5 minutes at room temperature, the reaction mixture was cooled to 0 C, and 1-bromo-3-(difluoromethyl)-5- fluorobenzene (612 mg, 2.72 mmol) was added at 0 C. The resulting mixture was stirred at 0 C for 1 hour, and then the mixture was added to a solution of (2S,3S,4R,5R)-5-(4-chloro-7H- pyrrolo[2,3-d]pyrimidin-7-yl)-2-(methoxy(methyl)carbamoyl)-3-methyltetrahydrofuran-3,4-diyl diacetate (200 mg, 0.454 mmol) in THF (3.0 mL) at 0 C. The resulting mixture was stirred for 10 minutes at 0 C. The reaction was quenched with acetic acid (390 muL, 6.81 mmol), and the resulting mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and then washed with 1 N citric acid. The organic layer was dried over Na2SO4, and the organic solvent was removed under reduced pressure. The crude material was then purified by flash column chromatography (EtOAc/EtOH (3:1) in hexanes, 5 to 100%) to yield (2S,3S,4R,5R)-5-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(3-(difluoromethyl)-5- fluorobenzoyl)-3-methyltetrahydrofuran-3,4-diyl diacetate as a solid. MS: 526 [M+H]+.

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; MERCK SHARP & DOHME CORP.; MACHACEK, Michelle; WITTER, David; HUANG, Chunhui; KAWAMURA, Shuhei; SCHNEIDER, Sebastian; WAN, Murray; (117 pag.)WO2020/33285; (2020); 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. 627526-90-3, name is 1-Bromo-3-(difluoromethyl)-5-fluorobenzene, This compound has unique chemical properties. The synthetic route is as follows., HPLC of Formula: C7H4BrF3

Intermediate CZ: 2-(3-(difluoromethyl)-5-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane A solution of PdCl2(dppf)-DCM adduct (0.399 g, 0.489 mmol), bis(pinacolato) diboron (2.73 g, 10.76 mmol), 1-bromo-3-(difluoromethyl)-5-fluorobenzene (Oakwood Chemicals, 2.200 g, 9.78 mmol) and potassium acetate (3.84 g, 39.1 mmol) in 35 mL DMF was heated to 100 C. overnight. The reaction mixture was then diluted with DCM and was washed with water. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by silica gel column chromatography (0-70% EtOAc/heptane) gave 2-(3-(difluoromethyl)-5-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.64 g, 6.03 mmol, 61.6% yield) as a yellow oil. 1H NMR (Acetone) ?: 7.72-7.78 (m, 1H), 7.44-7.58 (m, 2H), 6.99 (s, 1H), 1.32-1.43 (m, 12H).

According to the analysis of related databases, 627526-90-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Amgen Inc.; Weiss, Matthew; Boezio, Alessandro; Boezio, Christiane; Butler, John R.; Chu-Moyer, Margaret Yuhua; Dimauro, Erin F.; Dineen, Thomas; Graceffa, Russell; Guzman-Perez, Angel; Huang, Hongbing; Kreiman, Charles; La, Daniel; Marx, Isaac E.; Milgrim, Benjamin Charles; Nguyen, Hanh Nho; Peterson, Emily; Romero, Karina; Sparling, Brian; US9212182; (2015); B2;,
Bromide – Wikipedia,
bromide – Wiktionary