Category: 446-59-3

Electric Literature of 446-59-3, 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. 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows.

Synthesis of 3-Bromo-2-fluoro-4-methoxy-benzaldehyde In a 3-neck 250 mL round bottomed flask equipped with nitrogen lines and a stir bar was placed 2-bromo-1-fluoro-3-methoxy-benzene (2.0 g, 9.75 mmol) and dichloromethane (48 mL). The solution was cooled in an ice water bath for 15 minutes and then titanium tetrachloride (5.02 mL, 45.8 mmol) and dichloromethyl methyl ether (1.32 mL, 14.6 mmol) were added and the reaction mixture was allowed to warm to room temperature and react for 2 hours. The reaction mixture was slowly added to ice water (250 mL) and extracted with dichloromethane (2*100 mL). The organic portions were combined, washed with a saturated sodium bicarbonate solution (75 mL), water (75 mL) and brine (75 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 1.67 g of Int-4 as an off-white solid in 74% yield. MS (ESI+): 233.2 (M+) Int-17Synthesis of 3-Bromo-2-fluoro-4-methoxy-benzaldehyde using titanium(IV)chlorideA solution of 2-bromo-3-fluoroanisol (5.00 g, 24.3 mmol) in dichloromethane (120 mL) was cooled to 0 C. in a salt-ice bath and purged with nitrogen. The reaction was allowed to stir 15 min under nitrogen. To the reaction was added titanium(IV)chloride (23.1 g, 122 mmol), followed by a,a-dichloromethyl-methylether (4.21 g, 36.6 mmol) at 0 C. under nitrogen. The reaction was allowed to warm to room temperature and stirred for 22 h. The red solution was poured into ice water (600 mL), and extracted into dichloromethane (3×200 mL). The organic extracts were combined, washed with saturated aqueous sodium bicarbonate (2×400 mL), water (2×400 mL), and brine (400 mL), dried over sodium sulfate, filtered, and the solvent removed under vacuum to give wet product. The product was dried in a vacuum oven at 80 C. overnight to give Int-17 (5.75 g, quantitative yield).1H NMR (400 MHz CDCl3) delta 10.22 (s, 1H), 7.86 (dd, J=8.8 Hz, 7.6 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 4.01 (s, 3H). Synthesis of 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30). In a 3-necked 250 mL round-bottomed flask equipped with nitrogen lines and a stir bar was placed 2-bromo-1-fluoro-3-methoxy-benzene (I-29, 2.0 g, 9.75 mmol) and dichloromethane (48 mL). The solution was cooled in an ice water bath for 15 minutes and then titanium tetrachloride (5.02 mL, 45.8 mmol) and dichloromethyl methyl ether (1.32 mL, 14.6 mmol) were added and the reaction mixture was allowed to warm to room temperature and react for 2 hours. The reaction mixture was slowly added to ice water (250 mL) and extracted with dichloromethane (2×100 mL). The organic portions were combined, washed with a saturated sodium bicarbonate solution (75 mL), water (75 mL) and brine (75 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 1.67 g of 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30) as an off-white solid in 74% yield. MS (ESI+): 233.2 (M+).

The chemical industry reduces the impact on the environment during synthesis 2-Bromo-1-fluoro-3-methoxybenzene. I believe this compound will play a more active role in future production and life.

Reference:
Patent; DECODE GENETICS EHF; US2009/136473; (2009); A1;,
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Adding a certain compound to certain chemical reactions, such as: 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, belongs to ethers-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 446-59-3, COA of Formula: C7H6BrFO

A flame dried round bottle (evacuated under vacuum and filled with N2 ) was fitted with mechanical stirring, and charged with tert-butyl (S)-4-(6-chloro-8- fluoroquinazolin-4-yl)-3-methylpiperazine-1-carboxylate (685 mg, 1.80 mmol, 1.0 eq.) solution in dry THF. Bis(2,2,6,6-tetramethylpiperidinyl)zinc, lithium chloride, magnesium chloride complex ((TMP)2Zn?2 MgCl2?2 LiCl) (0.35 M solution in THF/toluene, 1.0 eq. ) was dropwise added. The reaction was allowed to stir for 45 min at RT and then degassed by bubbling nitrogen through the solution for 15 min. Solid 2- bromo-1-fluoro-3-methoxybenzene (1.0 eq.) and CPhos 3rd generation precatalyst (0.1 eq.) were added, and the resulting mixture was stirred at 40 C for 16 h. The reaction mixture was concentrated in vacuo, dissolved in ethyl acetate, cooled in an ice bath, and quenched with a 1:1 solution of saturated ammonium chloride and H2O. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (stepwise gradient of 20%-30% EtOAc in hexanes) to afford the desired product (504 mg, 56% yield).

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

Reference:
Patent; ARAXES PHARMA LLC; LI, Liansheng; FENG, Jun; LONG, Yun Oliver; LIU, Yuan; WU, Tao; REN, Pingda; LIU, Yi; (335 pag.)WO2016/164675; (2016); A1;,
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Related Products of 446-59-3, A common heterocyclic compound, 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, molecular formula is C7H6BrFO, 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 the dried reaction flask was added magnesium dust (600 mg, 24.9 mmol), a small portion of iodine and anhydrous tetrahydrofuran (10 mL), and the reflux condenser was charged and protected with nitrogen. -methoxybenzene (0.5 g) followed by the addition of 2-bromo-1-fluoro-3-methoxybenzene (2.5 g, 12.2 mmol) and freshly distilled 1,3-cyclopentadiene (1.05 g, 17.56 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) and placed in a constant pressure dropping funnel to slowly dropwise and the reaction system was kept slightly refluxed. After completion of the dropwise addition, the reaction system was heated to reflux for 1 hour. The reaction was quenched with saturated aqueous ammonium chloride (10 mL) and extracted with ethyl acetate (60 mL x 2). The organic phase was washed with saturated brine (30 mL) and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the crude product was purified by silica gel column chromatography (eluted with petroleum ether) to give the title compound (1.43 g, 56%) as a colorless liquid

The synthetic route of 446-59-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Guangdong Dongyangguang Pharmaceutical Co., Ltd.; Dongguan Dongyangguang Pharmaceutical Research And Development Co., Ltd.; Zhou Pingjian; Wang Xiaojun; Yang Chuanwen; Lin Jihua; Cao Shengtian; Yang Xinye; Zhang Yingjun; (34 pag.)CN106916091; (2017); A;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Application of 446-59-3, A common heterocyclic compound, 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, molecular formula is C7H6BrFO, 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.

Intermediate 1-40fluoro-phenol (1-40)To a solution of 2-bromo-3-fluoroanisole [C.A.S. 935285-66-8] (1 g, 4.48) in DCM (2 mL), BBr3 (17.93 mL, 17.93 mmol) was added dropwise at 0C. The reaction was stirred 2 h at r.t. Then the excess of BBr3 was quenched dropwise with water at 0C, the organic layer was separated, dried (Na2S04), filtered and the solvent evaporated in vacuo to yield intermediate 1-40 (0.94 g, quant, yield) that was used as such in the next reaction step

The synthetic route of 446-59-3 has been constantly updated, and we look forward to future research findings.

Electric Literature of 446-59-3, 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. 446-59-3 name is 2-Bromo-1-fluoro-3-methoxybenzene, 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-bromo-3-fluoroanisole (25 g), hexamethylenetetramine (34.2 g), and trifluoroacetic acid (150 mL) was stirred at 90C for 27 hours. The reaction mixture was allowed to cool to room temperature, and then 1 M hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, and then the organic layer was concentrated to about half of its volume. To the concentrated organic layer was added aqueous sodium hydroxide, and then the organic layer was separated from the mixture and washed with brine. The organic layer was dried over anhydrous sodium sulfate, and filtrated, and the solvent was removed. The obtained crude product was purified by silica gel column chromatography (heptane : ethyl acetate = 94 : 6 to 73 : 27) to afford the title compound as a white solid (22.3 g).1H-NMR (CDCl3) delta: 4.01 (3H, s), 6.82 (1H, d, J = 8.8 Hz), 7.85 (1H, dd, J = 8.8, 7.7 Hz), 10.22 (1H, d, J = 0.7 Hz).

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

Reference:
Patent; OTSUKA PHARMACEUTICAL CO., LTD.; KATOH, Takahiro; IIDA, Masatoshi; TERAUCHI, Yuki; YAMAGUCHI, Kazuya; HIROSE, Toshiyuki; YOKOYAMA, Fumiharu; NISHIMORI, Hikaru; OBUCHI, Yutaka; NABESHIMA, Hiroshi; TAKAKI, Emiri; (250 pag.)WO2017/150654; (2017); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Some common heterocyclic compound, 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, molecular formula is C7H6BrFO, 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. Recommanded Product: 446-59-3

2-Bromo-3-fluoro anisole (10 g, 48.77 mmol) was dissolved in DCM (200 mL) and cooled to about -78 C. To the solution was added BBr3 (11.53 mL, 121.9 mmol) in one portion. The mixture was warmed to r.t. and stirred overnight. The mixture was partitioned between water and DCM (50 mL), and the aqueous layer was back extracted with DCM (200 mL). The combined organics were dried (NaSO4), filtered and concentrated to give about 9.32 g of the product as a dark oil. MS found 188.9 (M-1)

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 446-59-3, its application will become more common.

Reference:
Patent; Briner, Karin; Doecke, Christopher William; Mancuso, Vincent; Martinelli, Michael John; Richardson, Timothy Ivo; Rothhaar, Roger Ryan; Shi, Qing; Xie, Chaoyu; US2004/82590; (2004); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Adding a certain compound to certain chemical reactions, such as: 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, belongs to ethers-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 446-59-3, Computed Properties of C7H6BrFO

To a solution of the above compound (58mg, 0. 224MMOL) in CH, CI (LML) cooled over dry ice/acetone bath was added boron TRIBROMIDE (224UL, 0. 224MMOL) and stirred over night at room temperature. After this time, the mixture was treated with methanol (3X5ML) and concentrated in vacuo to give 2-(1,1-dioxido-1, 2-thiazinan-2-yl) -3-fluorophenol. Low resolution mass spectrometry: (M+H+)= 246.16. 1H NMR (400MHZ, CDC13) 8 7.19 (dd, 1H, J=8.4 and 15HZ), 6.81 (d, 1H, J=8.4Hz), 6.70 (t, 1H, lOHz), 3.82-3. 90 (M, 1H), 3.60-3. 68 (m, 1H), 3.34-3. 43 (M, 1H), 3.26-3. 34 (M, 1H), 2.34-2. 43 (m, 2H), 1.94-2. 08 (M, 1H) and 1.77-1. 89 (M, 1H) ppm.

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, 2-Bromo-1-fluoro-3-methoxybenzene, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; MERCK & CO., INC.; WO2005/16886; (2005); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

446-59-3, A common heterocyclic compound, 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, molecular formula is C7H6BrFO, 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: The 2-bromo-1-ethoxy-4-fluoro-benzene (0.1 mol) was dissolved in THF (25 ml). The solution was cooled to -75 C and a solution of n-BuLi (9.73 ml, 2.4 M in hexane) was added slowly. The mixture was stirred for 30 min at -75 C. Trimethylborate (0.1 mol) was added within 5 min. Acetic acid (0.1 mol) and a 30% solution of H2O2 (0.1 mol) were added sequentially. The mixture was stirred for 30 min at 0 C and for 3 h at room temperature. Water was added and the mixture was extracted with ethyl acetate. The crude product was purified by column chromatography to yield the objected compound.

The synthetic route of 446-59-3 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Heng; Xu, Xiangqing; Chen, Yin; Qiu, Yinli; Liu, Xin; Liu, Bi-Feng; Zhang, Guisen; European Journal of Medicinal Chemistry; vol. 89; (2015); p. 524 – 539;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem