Category: 142808-15-9

Synthetic Route of 142808-15-9,Some common heterocyclic compound, 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, molecular formula is C7H3BrF4, 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 cyclopropylmethanol (2.22 g, 31 mmol) in THF (100 mL) at 0C was added sodium hydride (60% dispersion in oil, 2.06 g, 51 mmol) in portions and stirred at room temperature for 30 minutes, followed by addition of 4-bromo-2-fluoro-l-(trifluoromethyl)benzeneare (295A) (5.0 g, 20.5 mmol). The mixture was stirred at room temperature for 16 hours, quenched with water (50 mL), and extracted with EtOAc (50 mL x 3). The combined organic phases was washed with brine (50 mL), dried over sodium sulphate, concentrated, and purified by column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to furnish Compound 295B. LC-MS (ESI) m/z: non-ionizable compound under routine conditions used;1H-NMR (CDCb, 400 MHz): d (ppm) 0.39 (q, J= 4.9 Hz, 2H), 0.64 (q, J= 5.9 Hz, 2H), 0.81 – 0.91 (m, 1H), 3.91 (t, j= 8.1 Hz, 2H), 7.03 – 7.18 (m, 2H), 7.41 (d, J = 8.2 Hz, 1H).

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-fluorobenzotrifluoride, its application will become more common.

Reference:
Patent; BIOMARIN PHARMACEUTICAL INC.; WANG, Bing; CHAO, Qi; (737 pag.)WO2019/133770; (2019); A2;,
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. 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 4-Bromo-2-fluorobenzotrifluoride

5-[4-Fluoro-3-(trifluoromethyl)phenyl]spiro[cyclohexane-1,3-[3H]indol]-2(1H)-one was prepared from (2′-oxo-2,3-dihydrospiro[cyclohexane-1,3′-[3H]indol]-5′-yl)boronic acid (2.5 g, 10 mmol) and 5-bromo-2-fluoro-trifluoromethylbenzene (2 g, 8 mmol) as described for Example 5, to afford the title compound (0.87 g, 30%) as a solid: mp. 222 C.; 1H NMR (DMSO-d6) delta 1.5-1.8 (m, 8 H), 1.8-2.0 (m, 2 H), 6.92 (d, 1 H, J=8.13 Hz), 7.51 (dd, 1 H, J=8.13, 1.76 Hz), 7.55 (dd, 1 H, J=10.54, 9.01 Hz) 7.72 (d, 1 H, J=1.76 Hz), 7.90 (dd, 1 H, J=7.03, 2.20 Hz), 7.98 (m, 1 H) and 10.39 (s, 1 H); MS (EI) m/z 363 (M+).

According to the analysis of related databases, 142808-15-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; American Home Products Corporation; Ligand Pharmaceuticals, Inc.; US6355648; (2002); B1;,
Bromide – Wikipedia,
bromide – Wiktionary

142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, 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. Formula: C7H3BrF4

Example 26 Synthesis of TRV 1 158[00166] TRV 1158 – phenyl(4-(3-(pyrrolidin- l -yl)-4-(trifluoromethy])phenyl)piperazin- l – yl)methanone[00167] Scheme for TRV 1 158DIPEA / N P[00168] A mixture of 4-bromo-2-fluorobenzotrifluoride ( l .5 l l g, 6.2 mmol), pyrrolidine (0.62 mL, 7.46 mmol), DIPEA ( 1.6 mL, 9.33 mmol) and NMP (8 mL) were sealed in a tube and heated to 120 C overnight. The solution was cooled to room temperature and diluted with water and EtOAc. The layers were separated and the aqueous layer was back-extracted with EtOAc (3x). The combined organic layers were then washed successively with H2O, IN HCl(aq), saturated NaHC03(aq), H2O, and brine before drying with Na2SC>4. The mixture was filtered and concentrated to give a crude oil, which was purified via flash chromatography (5 % EtOAc / hexane) to give 0.9667 g (53 % yield) of desired product. This bromo-intermediate (0.5312 g, 1.8 mmol), benzoylpiperazine hydrochloride (0.4987 g, 2.2 mmol) and NaO/Bu (0.5189 g, 5.4 mmol) were charged to a flask which was subsequently purged and evacuated with argon (3 cycles). Toluene (5.4 mL) and NMP (3.2 mL) were then added and the solution was degassed for 30 minutes before added Pd2(dba)3 (0.033 g, 0.036 mmol) and BINAP (0.045 g, 0.072 mmol) all at once. The flask was then heated to 100 C overnight under argon. The mixture was cooled to room temperature and diluted with EtOAC before filtering through Celite. The organic layer was then washed successively with H20, IN HCl(aq), saturated NaHC03(aq), H2O, and brine before drying with Na2S04. The mixture was filtered and concentrated to give 0.5081 g of crude oil. The oil was purified via flash chromatography (45 % EtOAc / hexane) to give another crude oil that was slightly impure. This oil was crystallized from EtOAc (solvent) and hexane (anti-solvent) to give 0.101 g of white crystals of TRV 1158, phenyl(4-(3-(pyrrolidin-l -yl)-4- (trifluoromethyl)phenyl)piperazin- l-yl)methanone. NMR (500 MHz, DMSO) delta = 7.47-7.41 (m, 5H), 7.35 (d, J = 8.5 Hz, 1 H), 6.49 (dd, J = 8.5, 1.5 Hz, 1 H), 6.46 (m, 1 H), 3.72 (br s, 2H), 3.45 (br s, 2H), 3.30 (br s, 4H), 3.23-3.20 (m, 4H), 1.88- 1.83 (m, 4H).

The synthetic route of 142808-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; TREVENTIS CORPORATION; REED, Mark, A.; YADAV, Arun; BANFIELD, Scott, C.; BARDEN, Christopher, J.; WO2012/119035; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 142808-15-9, 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. 142808-15-9 name is 4-Bromo-2-fluorobenzotrifluoride, 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.

Into a 50 mL dry, round bottom flask fitted with a magnetic stirring bar, a dropping funnel (25 mL) and a refluxing condenser was placed magnesium turnings (129 mg, 5.3 mmol) and anhydrous diethyl ether (4 mL). Anhydrous diethyl ether (16 mL) was added to the dropping funnel followed by 4-bromo- 2-fluoro-1-(trifluoromethyl)benzene (1.17 g, 4.8 mmol). A portion of the 4- bromo-2-fluoro-1-(trifluoromethyl)benzene solution (2 mL) as well as iodine (5 mg) was added to the flask which was then heated to reflux and stirred. Heating was stopped and the remainder of the 4-bromo-2-fluoro-1- (trifluoromethyl)benzene solution was added dropwise to the flask at such a rate that the solvent refluxed gently (about 10 minutes). After the addition was complete, the reaction was heated to reflux for 2 hours. The mixture was cooled to -78 C and a solution of 2-(2,6,6-trimethylcyclohex-1- enyl)acetaldehyde (200 mg, 1.2 mmol) in diethyl ether (3 mL) was added dropwise via syringe. The reaction was allowed to warm to room temperature and stirred for 4 hours. The reaction was quenched by addition of saturated aqueous ammonium chloride (10 mL). The mixture was diluted with water (20 mL) and the organics were extracted with diethyl ether (30 mL x 2). The combined organic phase was washed with brine (60 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleumether/ethyl acetate = 100/1 ) to afford the title compound as a yellow oil (138 mg, Yield: 35%). Rf = 0.6 (10:1 petroleum ether/ethyl acetate); 1H NMR (400 MHz, CDCI3) delta 7.57 (t, J = 7.6 Hz, 1 H), 7.30-7.23 (m, 2H), 4.89 (t, J = 7.4 Hz, 1 H), 2.48-2.46 (m, 2H), 2.22 (d, J = 1 .2 Hz, 1 H), 2.12-1.96 (m, 2H), 1.68 (s, 3H), 1 .68-1 .62 (m, 2H), 1 .51 -1 .48 (m, 2H), 1 .07 (s, 3H), 1.06 (s, 3H) ppm; Mass spectrum (ESI +ve) m/z 331 (M + H+).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 4-Bromo-2-fluorobenzotrifluoride, and friends who are interested can also refer to it.

Reference:
Patent; BIKAM PHARMACEUTICALS, INC.; QUACH, Tan; BERMAN, Judd; GARVEY, David, S.; WO2013/81642; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 142808-15-9, These common heterocyclic compound, 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, 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.

Place 4-bromo-2-fluorotrifluorotoluene (29.2 g, 120 mmol, 1 eq.) In a dropping funnel and set aside. Diisopropylamine (14.6g, 144mmol, 1.2eq.) And 220ml of tetrahydrofuran were added to the reaction flask, cooled to -78 C, and n-butyllithium (52.8ml, 132mmol, 1.1eq.) Was added dropwise under the protection of nitrogen. After the dropwise addition, the mixture was stirred at 25 C for 1 hour. Recool to -78 C and add 4-bromo-2-fluorotrifluorotoluene dropwise. After the dropwise addition, the mixture was stirred at -78 C for 2 hours. Iodomethane (18.7g, 132mmol, 1.1eq.) Was added dropwise, and the temperature was gradually raised to 25 C for 16 hours.[0058]After the reaction was completed, it was cooled in an ice water bath, and 150 ml of saturated ammonium chloride solution was added dropwise for quenching. It was extracted with ethyl acetate, and the organic phase was concentrated to obtain 26.8 g of yellow oily 1-bromo-3-fluoro-2-methyl-4- (trifluoromethyl) benzene in 87% yield. Used directly in the next step.

Statistics shows that 4-Bromo-2-fluorobenzotrifluoride is playing an increasingly important role. we look forward to future research findings about 142808-15-9.

Reference:
Patent; Ali Biological New Materials (Changzhou) Co., Ltd.; Shi Jianyun; Xu Yibo; Shi Hongliang; Dai Hongsheng; Zhang Jun; (6 pag.)CN110885290; (2020); A;,
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. 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride belongs to bromides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below. name: 4-Bromo-2-fluorobenzotrifluoride

0.4 g of t-butoxysodium, 13.7 mg of Pd2(dba)3, and 17.7 mg of 2-(dicyclohexylphosphino)-2′-(N,N-dimethylamino)biphenyl were added to 11 ml of toluene solution containing 1 g of the free form of the compound (F) obtained above and 0.73 g of 4-bromo-2-fluorobenzotrifluoride and the entire mixture was refluxed overnight under nitrogen atmosphere. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. After being washed with water and dried with anhydrous magnesium sulfate, the organic layer was filtered and then vacuum-concentrated. The residue was purified by column chromatography (developing solution: mixed solvent of n-hexane and ethyl acetate) to obtain 0.54 g of the target compound. Viscous oil 1H-NMR(CDCl3, deltappm):1.08(t, 3H), 1.81-1.97(m, 4H), 2.04-2.23(m, 4H), 2.45(q, 2H), 3.97(t, 2H), 4.19(brs, 2H), 4.57(brt, 1H), 6.44-6.51(m, 2H), 6.76(d, 1H), 7.13(s, 1H), 7.16(d, 1H), 7.38(t, 1H)

The synthetic route of 142808-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NIPPON SODA CO., LTD.; HAMAMOTO, Isami; TAKAHASHI, Jun; YANO, Makio; KAWAGUCHI, Masahiro; HANAI, Daisuke; IWASA, Takao; EP1932844; (2015); B1;,
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. 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, A new synthetic method of this compound is introduced below., Product Details of 142808-15-9

Into a 10000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed tetrahydrofuran (5000 mL), NH(i-Pr)2 (249 g, 1.20 equiv). This was followed by the addition of n-BuLi (905 mL, 1.10 equiv) dropwise with stirring in 30 min at -70C. The resulting solution was stirred for 0.5 hr at -30C. To this was added 4-bromo-2-fluoro- l-(trifluoromethyl)benzene (500 g, 2.06 mol, 1.00 equiv) dropwise with stirring at -78C in 2 hr. The resulting solution was stirred for 2 hr at -78C. The reaction was then poured into 1000 g of C02(s) at -70C. The pH value of the solution was adjusted to 3 with hydrogen chloride (2N) (1.5 mol/L). The resulting solution was extracted with 3×2000 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 301 g (50%) of 6-bromo-2-fluoro-3-(trifluoromethyl)benzoic acid as a white solid.

The synthetic route of 142808-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; MANDAL, Mihir; TANG, Haifeng; XIAO, Li; SU, Jing; LI, Guoqing; YANG, Shu-Wei; PAN, Weidong; TANG, Haiqun; DEJESUS, Reynalda; HICKS, Jacqueline; LOMBARDO, Matthew; CHU, Hong; HAGMANN, William; PASTERNAK, Alex; GU, Xin; JIANG, Jinlong; DONG, Shuzhi; DING, Fa-Xiang; LONDON, Clare; BISWAS, Dipshikha; YOUNG, Katherine; HUNTER, David, N.; ZHAO, Zhiqiang; YANG, Dexi; WO2015/112441; (2015); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, 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: 4-Bromo-2-fluorobenzotrifluoride

step 2: To a solution of 4-bromo-2-fluoro-l-(trifluoromethyl)benzene (4.854 g, 19.98 mmol) and ether (50 mL) cooled to -78 C was added butyl lithium (7.990 mL, 19.98 mmol) slowly over 10 min. The reaction was transferred via cannula to a solution of 74 (4.30 g, 16.65 mmol) in THF (50 mL) cooled to -78 C. The reaction was stirred for 10 min after all aryl lithium was added. The reaction was quenched with water and extracted with DCM. The organic layer was concentrated and the crude product purified by Si02 chromatography eluting with an EtOAc/hexane (1 to 5% EtOAc). A close running impurity was not removed by this purification. A Si02 column was run eluting with an Et20/hexane gradient (1 to 3% Et20). The impurity was still present and the compound was finally purified on a SP4 reverse phase column chromatography eluting with MeCN/water gradient (65 to 100% MeCN) to afford 2.105 g (33.2%) of (R)-tert-butyl 2-(3-fluoro-4-(trifluoromethyl)benzoyl)-pyrrolidine-l-carboxylate (76).

The synthetic route of 142808-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ARRAY BIOPHARMA INC.; GENENTECH, INC.; BLAKE, James F.; CHEN, Huifen; CHICARELLI, Mark Joseph; DEMEESE, Jason; GARREY, Rustam; GAUDINO, John J.; KAUS, Robert J.; KOLAKOWSKI, Gabrielle R.; MARLOW, Allison L.; MOHR, Peter J.; REN, Li; SCHWARZ, Jacob; SIEDEM, Christopher S.; THOMAS, Allen A.; WALLACE, Eli; WENGLOWSKY, Steven Mark; WO2012/118850; (2012); 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. 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, A new synthetic method of this compound is introduced below., Recommanded Product: 142808-15-9

A) ethyl 2-((diphenylmethylene)amino)-2-(3-fluoro-4-(trifluoromethyl)phenyl)acetate A mixture of ethyl 2-((diphenylmethylene)amino)acetate (2.94 g), 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (2.43 g) and tripotassium phosphate (6.37 g) in toluene (30 mL) was argon-substituted, and bis(tri-tert-butylphosphine)palladium (0) (0.256 g) was added at room temperature. The reaction mixture was stirred at 80 C. for 21 hr, bis(tri-tert-butylphosphine)palladium (0) (0.256 g) was added, and the mixture was stirred at 100 C. for 16 hr. To the reaction mixture were added water and ethyl acetate, and the insoluble material was filtered off. The organic layer of the filtrate was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (3.02 g). MS (API+): [M+H]+430.1.

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; TAKEDA PHARMACEUTICAL COMPANY LIMITED; Kawasaki, Masanori; Mikami, Satoshi; Nakamura, Shinji; Negoro, Nobuyuki; Ikeda, Shuhei; Nomura, Izumi; Ashizawa, Tomoko; Imaeda, Toshihiro; Seto, Masaki; Sasaki, Shigekazu; Marui, Shogo; Taniguchi, Takahiko; (130 pag.)US2016/159808; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 142808-15-9, These common heterocyclic compound, 142808-15-9, name is 4-Bromo-2-fluorobenzotrifluoride, 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 80A2-[3-Fluoro-4-(trifluoromethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane A mixture of 25 g (99.8 mmol) of 4-bromo-2-fluoro-1-(trifluoromethyl)benzene in 500 ml of dioxane was admixed under argon at RT with 27.8 g (109.8 mmol) of 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bis-1,3,2-dioxaborolane, 2.91 g (3.99 mmol) of 1,1-bis(diphenylphosphine)-ferrocenedichloropalladium(II) dichlormethane complex and with 29.38 g (299.4 mmol) of potassium acetate. The reaction mixture was stirred below 100 C. for several hours until conversion was substantially complete. The mixture was filtered through Celite and admixed with water. After addition of ethyl acetate and phase separation, the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by flash chromatography (silica gel-60, eluent: cyclohexane/ethyl acetate 3:1). This gave 18.22 g of crude product in 73% purity (LC-MS), which was reacted without any further purification steps.1H NMR (400 MHz, DMSO-d6): delta=7.82 (dd, 1H), 7.67 (d, 1H), 7.59 (d, 1H), 1.32 (s, 12H).

The synthetic route of 142808-15-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BAYER SCHERING PHARMA AKTIENGESELLSCHAFT; US2011/21489; (2011); A1;,
Bromide – Wikipedia,
bromide – Wiktionary