Category: 450-88-4

450-88-4, These common heterocyclic compound, 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, 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.

A total of 1.64 ml of diisopropylamine was dissolved in 27 ml of tetrahydrofuran, 6.8 ml of a 1.57 M solution of n-butyllithium in hexane was added at -50C under stirring, and the mixture was stirred at -30C for 30 minutes. After cooling to -60C, 2 g of 1-bromo-4-fluoro-2-methoxy-benzene obtained in Production Example II-1-a was added and the mixture was stirred at -60C for 1 hour. Then, 1.55 ml of 3-fluoro-benzaldehyde was added, followed by stirring for 1 hour. Saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with diethyl ether. The resulting organic layer was washed with brine, dried over magnesium sulfate and the solvent was evaporated, to give 2.4 g of the title compound as a yellow-brown oil.1H-NMR ( 400 MHz, CDCl3 ) d 3.52 ( 3H, s ), 3.56 ( 1H, d, J = 10.4 Hz ), 6.16 ( 1H, d, J=11.6Hz ), 6.86 ( 1H, t, J = 8.8 Hz ), 6.92 – 6.99 ( 1H, m ), 7.07 – 7.16 ( 2H, m ), 7.30 ( 1H, td, J = 8.0, 6.0 Hz ), 7.51 ( 1H, dd, J = 8.8, 6.0 Hz )

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 450-88-4.

Reference:
Patent; Eisai Co., Ltd.; EP1380576; (2004); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 450-88-4, name is 1-Bromo-4-fluoro-2-methoxybenzene, A new synthetic method of this compound is introduced below., 450-88-4

Tris-(2-methoxy-4-fluorophenyl)phosphine (L4) preparation. Charge magnesium (Mg) turnings (1.18 g, 48.8 mmol) and five (5) mL THF under nitrogen into a 3-neck round-bottom flask equipped with a reflux condenser and heat the flask contents to 500C with a heating mantle. Add dropwise a solution of 2-bromo-5- fluoroanisol (5.00 g, 24.39 mmol) and 1 ,2-dibromoethane (0.51 g, 2.7 mmol) in THF (total volume of 15 mL) with stirring. Remove the heating mantle five (5) minutes after commencing the addition as the reaction heat becomes sufficient to maintain the reaction temperature. After completing the addition in about 50 minutes to yield a first mixture, reflux the first mixture for an additional 30 minutes to yield a brown solution. After allowing the brown solution to cool to room temperature, separate the brown solution from the unreacted Mg turnings by transferring the brown solution via a cannula into a 100 mL round-bottom flask under nitrogen. Cool the brown solution to -700C and add dropwise a solution Of PCl3 (1.038 g, 7.56 mmol) in seven (7) mL THF with stirring over a period of 30 minutes to yield a second mixture. Heat the second mixture to 500C and stir the second mixture for two (2) hours at 500C. After cooling flask contents to room temperature and transferring the flask into a glovebox, filter the second mixture and wash the filter with diethyl ether (20 mL) to obtain a filtrate. Remove volatiles from the filtrate under vacuum to yield a light brown solid. Dissolve this light brown solid in benzene under an inert nitrogen atmosphere to obtain a benzene solution and wash the benzene solution with deionized water (3 x 20 mL). Dry the organic layer over MgSO4 and then filter it to obtain a dry benzene solution. Remove benzene under vacuum to isolate an off-white solid, which is further purified by recrystallization from acetonitrile (1.60 g, 52.1 % yield). 1H NMR (C6D6): delta 2.99 (s, 3 H), 6.30-6.33 (m, IH), 6.49-6.52 (t of d, 3/HH = 8.2, 2.3, IH), 6.82-6.86 (m, IH). 31P NMR (C6D6, externally referenced using H3PO4): delta -38.9. 19F NMR (C6D6): -110.8 to -110.90 (m, IF).

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; DOW GLOBAL TECHNOLOGIES INC.; BRIGGS, John; PATTON, Jasson; VERMAIRE-LOUW, Sonet; MARGL, Peter; HAGEN, Henk; BEIGZADEH, Daryoosh; WO2010/19360; (2010); A2;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

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. 450-88-4 name is 1-Bromo-4-fluoro-2-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. 450-88-4

Intermediate Example Int20.014-(4-bromo-3-methoxyphenoxy)-1 -methylpiperidine To a stirred suspension of sodium hydride (1.76 g; 60% w/w sodium hydride in oil) in DMF (55 mL) was added 1 -methylpiperidin-4-ol (3.37 g) at 0 C. The mixture was stirred at room temperature for 30 minutes. 1 -bromo-4-fluoro-2- methoxybenzene (3.0 g) was added and the mixture was stirred at 100 C for 1 h. Water was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Aminophase-silica- gel chromatography gave 3.65 g of the title compound.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-4-fluoro-2-methoxybenzene, and friends who are interested can also refer to it.

Reference:
Patent; BAYER PHARMA AKTIENGESELLSCHAFT; SCHULZE, Volker; KOSEMUND, Dirk; SCHIROK, Hartmut; BADER, Benjamin; LIENAU, Philip; WENGNER, Antje Margret; BRIEM, Hans; HOLTON, Simon; SIEMEISTER, Gerhard; PRECHTL, Stefan; KOPPITZ, Marcus; STOeCKIGT, Detlef; PRIEN, Olaf; WO2011/157688; (2011); A1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem