Month: June 2021

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

Reference of 1337523-99-5, A common heterocyclic compound, 1337523-99-5, name is 6-Bromo-1,2,3,4-tetrahydronaphthalen-1-amine, molecular formula is C10H12BrN, 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.

In a 50-mL round-bottom flask, to a solution of 6-bromo-l ,2,3,4-tetrahydronaphthalen-l -amine (4.34 g, 19.17 mmol, 1.00 equiv) and TEA (3.07 g, 30.33 mmol, 1.58 equiv) in dichloromethane (80 mL) was added (Boc)20 (6.65 g, 30.47 mmol, 1.59 equiv) at 0 C. The resulting solution was stirred for 16 h at 25 C. After the reaction was done, it was quenched by the addition of water (10 mL) and the mixture was extracted with dichloromethane (3 x 20 mL). The combined organic layers were washed by brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified in a silica gel column eluting with dichloromethane in petroleum ether (5% to 20% gradient) to afford tert-butyl N-(6-bromo-l, 2,3,4- tetrahydronaphthalen-l -yl)carbamate as white oil (6.2g, 95% for two steps). MS: m/z = 269.9[M+H-56]-

The synthetic route of 1337523-99-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK PATENT GMBH; CALDWELL, Richard; LIU-BUJALSKI, Lesley; POTNICK, Justin; NEAGU, Constantin; KULKARNI, Shashank; JONES, Reinaldo; QIU, Hui; (238 pag.)WO2020/43638; (2020); 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. 1003-98-1, name is 2-Bromo-4-fluoroaniline, A new synthetic method of this compound is introduced below., Product Details of 1003-98-1

2-Bromo-4-fluoroaniline (0.54 g, 2.84 mmol) was dissolved in MeCN (14.21 ml). Ammonium thiocyanate (0.324 g, 4.26 mmol) was added to the reaction mixture followed by benzyltrimethylammonium tribromide (1.108 g, 2.84 mmol), and thereaction mixture was allowed to stir for 12 hours. The reaction mixture was diluted with saturated aqueous NaHCO3, and the solids were collected by suction filtration and washed with water to yield Intermediate 806A (0.700 g, 2.84 mmol, 100%). ?H NIVIR (4001V11{z, MeOH4) 7.41 (dd, J8.0, 2.5 Hz, 1H), 7.26 (dd, J8.9, 2.5 Hz, 1H). LC-MS. method H, RT = 0.81 mm, MS (ESI) m/z: 247/249 (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; BRISTOL-MYERS SQUIBB COMPANY; ZHANG, Xiaojun; PRIESTLEY, Eldon Scott; BATES, J. Alex; HALPERN, Oz Scott; REZNIK, Samuel Kaye; RICHTER, Jeremy M.; (1137 pag.)WO2018/13774; (2018); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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

Step A4-bromo-2-chloro-6-(trifluoromethyl)aniline[00296] 4-bromo-2-(trifluoromethyl)aniline (12.2 g, 50.8 mmol) was dissolved in acetonitrile (200 mL) before N-chlorosuccinimide (7.47 g, 55.9 mmol) was added and the mixture heated to 80 C. The reaction was stirred for 2 hours and allowed to cool to room temperature. The reaction mixture was quenched with water and extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The residue passed through a silica plug eluting with dichloromethane. The filtrate was concentrated to give the title compound (13.1 g, 94%) as a liquid. H NMR (400 MHz, DMSO- /6) delta ppm 7.78 (d, 1 H), 7.52 (d, 1 H), 5.92 (s, 2 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; GLAXOSMITHKLINE LLC; BANKA, Anna; CATALANO, John G; FANG, Jing; PEAT, Andrew James; TAI, Vincent; TURNER, Elizabeth; WO2011/97491; (2011); 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. 1435-51-4, name is 1,3-Dibromo-5-fluorobenzene, A new synthetic method of this compound is introduced below., Product Details of 1435-51-4

A solution of 28 (15.6 g, 0.05 mol) in Et2O (30 mL) was added dropwise at -78 C to a stirred solution of LDA, freshly prepared from diisopropylamine (5.5 g, 0.55 mol) and nBuLi (10 M, 5 mL, 0.05 mol) in THF (80 mL). After ca 30 min stirring at ca -78 C chlorodimethylsilane (5.0 g, 0.053 mol) was added slowly. The mixture was stirred for 30 min at -78 C and then was allowed to warm warm to ca. -50 C. 1 M aqueous H2SO4 (30 mL) was added with stirring. The organic phase was separated. The water phase was washed with Et2O (2 × 30 mL). The combined organic phase was dried over anhydrous MgSO4. It was filtered and evaporated under reduced pressure and the residue was subjected to a fractional distillation under reduced pressure. The crude product was obtained as a colorless liquid, b.p. 95-103 C (1 Tr). It tends to solidify partly when stored for a longer time at room temperature. Subsequent crystallization of this material from cold methanol (50 mL, -30 C) afforded pure product as a white solid, m.p. 28-30 C. Yield 13.5 g (73%). 1H NMR (400 MHz, CDCl3): delta 7.59 (s, 1H, Ph), 4.80-4.63 (m, 2H, SiH), 0.44 (dd, J = 3.9, 1.9 Hz, 12H, SiMe2) ppm. 13C NMR (101 MHz, CDCl3): delta 170.85 (d, J = 244.5 Hz), 132.84 (d, J = 3.5 Hz), 132.18 (d, J = 14.4 Hz), 124.42 (d, J = 38.8 Hz), -3.23 (d, J = 4.4 Hz) ppm. 19F NMR (376 MHz, CDCl3): delta -77.55 (m) ppm. Anal. Calcd for C10H15Br2FSi2 (370.20): C, 32.44; H, 4.08. Found: C, 32.23; H, 3.93.

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:
Article; Durka, Krzysztof; Laudy, Agnieszka E.; Charzewski, ?ukasz; Urban, Mateusz; St?pie?, Karolina; Tyski, Stefan; Krzy?ko, Krystiana A.; Luli?ski, Sergiusz; European Journal of Medicinal Chemistry; vol. 171; (2019); p. 11 – 24;,
Bromide – Wikipedia,
bromide – Wiktionary

Related Products of 556-96-7, 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. 556-96-7 name is 1-Bromo-3,5-dimethylbenzene, 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.

I.2 Synthesis Methods and Characterization of the CompoundsI2.1 Bis(3,5-Dimethylphenyl)Phosphinic Acid 1-Bromo-3,5-dimethylbenzene (13.63 g, 71.44 mmol, 97%) is added dropwise at room temperature to magnesium turnings (1.74 g, 71.44 mmol) in anhydrous THF (80 mL). Once the magnesium has dissolved completely, a solution of N,N-dimethylphosphoryl dichloride N(Me)2P(O)Cl2 (4.33 mL, 35.72 mmol) in anhydrous THF (10 mL) is added dropwise. To remove the salt formed in the reaction, the reaction mixture, after two hours, is added to an ice-cooled ammonium chloride solution (30 g in 500 mL of water). In a distillation apparatus, the THF is subsequently removed and the residue is boiled with concentrated HCl (75 mL) at 80 C. The resulting white solid is dissolved in aqueous NaOH (5.4 g, 300 mL of water) and the aqueous phase is extracted twice with diethyl ether. The clear aqueous phase is acidified again by adding concentrated HCl, in order to precipitate the phosphinic acid as a white solid in 70% yield (6.81 g).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-3,5-dimethylbenzene, and friends who are interested can also refer to it.

Reference:
Patent; BASF SE; KONINKLIJKE PHILIPS ELECTRONICS N.V.; OSRAM OPTO SEMICONDUCTORS GMBH; US2011/172423; (2011); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Related Products of 129316-09-2,Some common heterocyclic compound, 129316-09-2, name is 1,3-Dibromo-5-(tert-butyl)benzene, molecular formula is C10H12Br2, 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.

Preparative Example P23Step 1 : 2-(3-Bromo-5-(tert-butyl)phenyl)propan-2-ol (P23a) To a solution of 1 ,3-dibromo-5-ferr-butylbenzene (404 mg) in dry THF (10 mL) was added n- BuLi (0.84 mL) at -78C and after 20 min, acetone was added dropwise to the above solution at -78C and the mixture was stirred at this temperature for 30 min and at rt for 1 h, diluted with sat. NH4CI and extracted with EA (3 x 30 mL). The organic layer was dried over Na2S04, evaporated and purified by CC to give compound P23a (380 mg, 70%) as a white solid.

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-(tert-butyl)benzene, its application will become more common.

Reference:
Patent; PHENEX PHARMACEUTICALS AG; STEENECK, Christoph; KINZEL, Olaf; GEGE, Christian; KLEYMANN, Gerald; HOFFMANN, Thomas; WO2012/139775; (2012); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 33070-32-5, A common heterocyclic compound, 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, molecular formula is C7H3BrF2O2, 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 cold solution of 5-bromo-2,2-difluorobenzo[(f] [l ,3]dioxole (5.75 mL, 42.2 mmol) in tetrahydrofuran (80 mL) was added a 2.0 M solution of isopropylmagnesium chloride in tetrahydrofuran (28.1 mL, 56.1 mmol) within 5- 10 minutes while maintaining the temperature in the range of 10-20 C. The reaction mixture was stirred at the same temperature for another 15 minutes and then allowed to attain room temperature with continued overnight stirring. The reaction mixture was cooled with an ice bath, triisopropyl borate (12.74 mL, 54.9 mmol) was added dropwise over 2 minutes, and stirring at room temperature was continued for 30 minutes. The reaction mixture was cooled to 10 C and 10% H2SO4 solution (50 mL) was added slowly which resulted in a slight exotherm to 20 C. After stirring for 15 minutes, the mixture was partitioned between water and ethyl acetate, and the combined organic extracts were washed with saturated NaHCC>3 solution. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in 100 mL of teri-butyl methyl ether and cooled to 0 C. 30% Hydrogen peroxide solution in water (5.39 mL, 52.7 mmol) was added slowly, followed by water (60 mL), and the mixture was stirred overnight while warming up to ambient temperature. The reaction mixture was diluted with ethyl acetate and washed twice with sodium thiosulfate solution and brine. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified on silica gel(0-50% ethyl acetate in heptane) to give 6.43 g of the title compound as an amber oil.JH NMR (400 MHz, DMSO- ) delta ppm 9.75 (s, 1H), 7.12 (d, / = 8.7 Hz, 1H), 6.75 (d, / = 2.4 Hz, 1H), 6.52 (dd, / = 8.7, 2.5 Hz, 1H). MS (ESI-) mJz 173.1 (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; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; PLIUSHCHEV, Marina, A.; FROST, Jennifer, M.; TONG, Yunsong; BLACK, Lawrence, A.; XU, Xiangdong; SHI, Lei; ZHANG, Qingwei, I.; CHUNG, Seungwon; XIONG, Zhaoming; SWEIS, Ramzi, Farah; DART, Michael, J.; BROWN, Brian, S.; MURAUSKI, Kathleen; (673 pag.)WO2019/90069; (2019); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 51554-93-9, 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 51554-93-9 as follows.

General procedure: A 3-neck round-bottomed flask equipped with a thermometer and a condenser was flame-dried and flushed with Ar. The flask was then charged with Mg0 (1.1 eq.), a single I2 crystal and another vacuum/Ar cycle was performed. Et2O (C=0.65M) was added resulting in a bright orange suspension of Mg0 pellets. Phenyl octyl bromide (1.0 eq.) was then added in one portion and the suspension was heated via a heatgun until the internal temperature reached 32C and stabilized for 5-10s, indicating that the Grignard formation had started. The reaction was stirred at rt until disappearance of the starting material by 1H NMR analysis (e.g.?1h). (0031) The Grignard solution (3.0 eq., C=0.65M) was then syringed to another flask containing substrate (1.0. eq.) in dry Et2O (C=0.05M). The solution was stirred at rt until disappearance of the starting material by TLC analysis. Saturated aqueous NH4Cl solution was added and the aqueous layer was extracted x2 with EtOAc. The organic layers were collected, washed x1 brine, dried over Na2SO4, filtered, concentrated in vacuo.

According to the analysis of related databases, 51554-93-9, the application of this compound in the production field has become more and more popular.

Reference:
Article; Garsi, Jean-Baptiste; Sernissi, Lorenzo; Vece, Vito; Hanessian, Stephen; McCracken, Alison N.; Simitian, Grigor; Edinger, Aimee L.; European Journal of Medicinal Chemistry; vol. 159; (2018); p. 217 – 242;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 1003-98-1, A common heterocyclic compound, 1003-98-1, name is 2-Bromo-4-fluoroaniline, molecular formula is C6H5BrFN, 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.

General procedure: o-Bromaniline (1a, 0.2 mmol), benzoyl chloride (2a, 1.2 eq), Cu NPs (1.3 mg, 10 mol%), 1,10-phen(4.0 mg, 10 mol%), K2CO3 (2.0 equiv), and 1.5 mL of MeCN were added into a 5-mL sealed tubeunder N2. The mixture was stirred at 90 for 1 hour. Then, the reaction was stopped, and the reactionmixture was purified by flash column chromatography on silica gel (hexanes/EtOAc 15:1). Compound4a was obtained in >99 % of yield.

The synthetic route of 1003-98-1 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Wang, Yong; Wu, Chaolong; Nie, Shoujie; Xu, Dingjian; Yu, Min; Yao, Xiaoquan; Tetrahedron Letters; vol. 56; 49; (2015); p. 6827 – 6832;,
Bromide – Wikipedia,
bromide – Wiktionary