Category: 33070-32-5

Reference of 33070-32-5, 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. 33070-32-5 name is 5-Bromo-2,2-difluorobenzodioxole, 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 250 mL round bottom flask with stir bar was charged with toluene (100 mL), and the solvent was sparged with N2 for one hour. Trisodium phosphate (20.75 g, 127 mmol) was added, followed by bis(dibenzylideneacetone)palladium (0.970 g, 1.68 8 mmol). A solution of tri-tert-butylphosphine (0.683 g, 3.38 mmol) was added over 10 minutes via syringe, and the suspension was stirred for 50 minutes at 25C. 5-Bromo-2,2-difluorobenzo[dj[1,3jdioxole (10 g, 42.2 mmol) was added, and after stirring for 50 minutes at 25 C, ethyl 2-cyanoacetate (9.55 g, 84 mmol) was added over 5 minutes, followed by the addition of 1.5 mL of water. The reaction was heated at 75 C for 12 hours. Three additional vials were set up as described above. After completion of the reaction, all four reaction mixtures were combined. The reaction was cooled to 25 C and filtered over diatomaceous earth. The filtrate was concentrated, and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5/1) to provide the title compound (24.5 g, 48.5 % yield). ?H NMR (400 MHz, DMSO-d6) 6 ppm 1.15 – 1.23 (m, 3 H) 4.13 – 4.29 (m, 2 H) 7.30 (dd, J=8.38, 1.76 Hz, 1 H) 7.46 – 7.55 (m, 2 H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 5-Bromo-2,2-difluorobenzodioxole, and friends who are interested can also refer to it.

Reference:
Patent; ABBVIE S.A.R.L.; GALAPAGOS NV; CHAN, Vincent S.; KYM, Philip R.; SHEKHAR, Shashank; WANG, Xueqing; (89 pag.)WO2018/116185; (2018); 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

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. 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, A new synthetic method of this compound is introduced below., COA of Formula: C7H3BrF2O2

Example 1A 2,2-difluoro-2H-1,3-benzodioxol-5-ol To a mixture of 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (10 g, 42.2 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (2.028 g, 4.22 mmol) and potassium hydroxide (4.74 g, 84 mmol) was added degassed water (10 mL). The reaction mixture was sparged with a nitrogen stream for 5 minutes. To the reaction mixture was added a degassed solution of tris(dibenzylideneacetone)dipalladium(0) (0.773 g, 0.844 mmol) in dioxane (10 mL). The combined reaction mixture was sparged with nitrogen for 5-7 minutes. The reaction vial was capped and stirred at 100 C. overnight (16 hours). The reaction mixture was cooled to ambient temperature, and partitioned between ethyl acetate and 1 N HCl solution. The organic fractions were combined and washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo, maintaining a bath temp at or below 25 C. The residue was purified by flash chromatography using a 220 g silica gel cartridge, eluting with 25-75% dichloromethane/heptanes to afford 6.02 g of the title compound (82% yield). 1H NMR (400 MHz, CDCl3) delta ppm 5.51 (s, 1H), 6.50 (dd, J=8.6, 2.5 Hz, 1H), 6.63 (d, J=2.4 Hz, 1H), 6.90 (dd, J=8.7, 1.4 Hz, 1H); MS (ESI-) m/z 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; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Cowart, Marlon D.; Esmieu, William Ramesh; Gfesser, Gregory A.; Greszler, Stephen N.; Koenig, John R.; Kym, Philip R.; Liu, Bo; Malagu, Karine Fabienne; Patel, Sachin V.; Scanio, Marc J.; Searle, Xenia B.; Voight, Eric; Wang, Xeuqing; Yeung, Ming C.; (202 pag.)US2017/15675; (2017); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

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 33070-32-5 as follows. name: 5-Bromo-2,2-difluorobenzodioxole

To the dry reaction tankIn sulfolane 940g,Lithium bromide 130g,130g of cuprous cyanide was stirred evenly so that lithium bromide and cuprous cyanide dissolved, and then added5-Bromo-2,2-difluoro pepper ring 237g,The reaction was incubated at 135 8h,After the reaction was cooled to 20 C, water 2.9kg,Steam distillation of solid products, after drying 167g,The content of 167 g of 5-cyano-2,2-difluoro pepper ring was 99.3%, yield 91.2%.

According to the analysis of related databases, 33070-32-5, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Fuxin Aoruikai New Materials Co., Ltd.; Liu Min; Yang Yinxing; Chen Li; Liu Chunyu; Liu Wei; Qin Wenyi; (5 pag.)CN105153106; (2017); B;,
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. 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, A new synthetic method of this compound is introduced below., name: 5-Bromo-2,2-difluorobenzodioxole

Step 1: (S)-Methyl2-(tert-butoxycarbonyl)-3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) propanoate To a 25 mL RBF was added zinc powder (1.03 g, 15.8 mmol) and iodine (0.0161 g, 0.0633 mmol). The mixture was heated with a heat gun for 5 minutes and the resulting mixture was then flushed with nitrogen 3 times and allowed to cool to rt. A solution of (R)-methyl2-(tert-butoxycarbonyl)-3-iodopropanoate (3.47 g, 10.5 mmol) in 5 mL of DMF was added dropwise to the mixture over 3 minutes and the resulting grey slurry was stirred at 0 C. for 20 minutes before being warmed to rt. After stirring at rt for 30 minutes, 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (2.50 g, 10.5 mmol), Pd2(dba)3 (0.193 g, 0.211 mmol) and S(Phos) (0.346 g, 0.844 mmol) were added and the reaction mixture was heated to 40 C. for 2 hours. The resulting mixture was cooled to rt and partitioned between ethyl acetate (50 mL) and a solution of ~9:1 saturated ammonium chloride/ammonium hydroxide pH=9 (250 mL). The aqueous layer was extracted with ethyl acetate (3*100 mL) and the combined organic layers were washed with water, brine, and dried over sodium sulfate. Concentration of the filtered solvents and purification of resulting crude material by silica gel chromatography provided (S)-methyl 2-(tert-butoxycarbonyl)-3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propanoate (1.89 g, 49.9% yield) as a slightly brown oil.

The synthetic route of 33070-32-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Amgen Inc.; US2010/120774; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 33070-32-5, These common heterocyclic compound, 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, 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 89E 2.2-difluoro-1,3-benzodioxol-5-ylboronic acid A solution of 5-bromo-2,2-difluorobenzodioxole (1.18 g, 4.97 mmol) in anhydrous diethyl ether (8 mL) at -78 C. was treated with 2.5M n-BuLi in hexane (2.4 mL, 5.97 mmol), stirred for 1 hour, and treated with triisopropyl borate (1.5 mL, 6.46 mmol). The mixture was slowly warmed to room temperature and stirred for about 18 hours. The reaction was quenched with saturated NH4Cl/10% HCl and extracted with ethyl acetate. The combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was used directly without further purification. 1H NMR (CD3OD) delta 7.26-7.11 (m, 3H).

Statistics shows that 5-Bromo-2,2-difluorobenzodioxole is playing an increasingly important role. we look forward to future research findings about 33070-32-5.

Reference:
Patent; Claiborne, Akiyo K.; Gwaltney, II, Stephen L.; Hasvold, Lisa A.; Li, Qun; Li, Tongmei; Lin, Nan-Horng; Mantei, Robert A.; Rockway, Todd W.; Sham, Hing L.; Sullivan, Gerard M.; Tong, Yunsong; Wang, Gary; Wang, Le; Wang, Xilu; Wang, Wei-Bo; US2002/115640; (2002); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Synthetic Route of 33070-32-5, These common heterocyclic compound, 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, 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.

(0104) Firstly, 18.96 g (0.08 mol) of Compound 1 (5-Bromo-2,2-difluorobenzodioxol), 1.52 g (0.008 mol) of CuI, 26.88 g (0.48 mol) of KOH, 200 mL of polyethylene glycol (PEG 400), and 50 mL of water were added into a reaction bottle. Then, the mixture in the reaction bottle was heated to reflux under nitrogen for 48 hours. After the reaction completed, an extraction was performed by using ethyl acetate (EA)/sodium chloride aqueous solution. The organic phase of the extraction solution was collected and concentrated. A column chromatography was performed by using hexane/EA (hexane: EA=8:2) as a mobile phase. The mobile phase after column chromatography was concentrated by the rotary concentrator, and Compound 2 (light yellow liquid) was obtained. The reaction is as follows:

The synthetic route of 33070-32-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; DAXIN MATERIALS CORPORATION; LO, CHIH-YUAN; LIU, HSIN-CHENG; LAN, GUO-YU; WANG, CHUN-CHIH; (27 pag.)US2016/222295; (2016); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Reference of 33070-32-5, These common heterocyclic compound, 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, 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.

Preparation 67 2-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane To a solution of 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (1.5 g, 6.3 mmol) in N,N-dimethylformamide (12.7 mL) was added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.6 g, 6.3 mmol), potassium acetate (1.9 g, 19.0 mmol), and (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (0.3 g, 0.32 mmol). The reaction mixture was heated at 80 C. for 18 h, then the reaction mixture was diluted with Et2O and washed with water. The organic layers were separated, dried with Na2SO4, filtered, concentrated in vacuo, and purified by silica gel chromatography eluting with 0-100% acetone in hexanes to yield a brown oil (0.9 g, 50%): 1H NMR (400 MHz, DMSO-d6) delta 7.55 (d, J=8.0 Hz, 1H), 7.53 (s, 1H), 7.43 (d, J=8.0 Hz, 1H), 1.30 (s, 12H); 19F NMR (376 MHz, DMSO-d6) delta -49.26 (s); EIMS m/z 284.

The synthetic route of 33070-32-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Dow AgroSciences LLC; Eckelbarger, Joseph D.; Epp, Jeffrey B.; Fischer, Lindsey G.; Lowe, Christian T.; Petkus, Jeff; Roth, Joshua; Satchivi, Norbert M.; Schmitzer, Paul R.; Siddall, Thomas L.; US2014/274701; (2014); 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. 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, A new synthetic method of this compound is introduced below., SDS of cas: 33070-32-5

40 g (0.169 mol) of the 5-bromo-2,2-difluorobenzodioxole prepared in Example 1 and 108 g (121.5 ml) of tetrahydrofuran were placed in a 1 L reaction flask, and the mixture was stirred under a nitrogen atmosphere to cool the system to -10 C, control system temperature -10 ~ 0 C, A solution of 104 g (0.202 mol) of 20% isopropylmagnesium chloride in tetrahydrofuran was added dropwise to the system to control the dropping rate, and the dropwise addition was completed in about 3 hours. After the completion of the dropwise addition, the reaction was kept for 2 hours. The temperature was further lowered to -25 C, and 18.5 g (0.253 mol) of N,N-dimethylformamide was added dropwise, and the mixture was kept for 2 hours. Quenched by adding 200 ml of saturated ammonium chloride solution, adding 15% hydrochloric acid to adjust the pH value of 5-6, adding 250 g of dichloromethane to extract, layering, transfer the lower organic phase to 500 ml reaction flask at 60 C, and concentrate under reduced pressure until no fraction was obtained to give the intermediate product 2,2-difluoro-1,3-benzodioxan-5-carbaldehyde 28.6 g (0.153 mol). The system was cooled to 20-30 C, and 180 g of absolute ethanol was added.Under nitrogen protection, stirring was started, and 2.55 g (0.067 mol) of sodium borohydride was slowly added to the system in portions, and the addition was completed in about 3 hours. After the addition of heat for 30 min, the reaction was quenched by adding 800 g of water, and then extracted with 205 g of dichloromethane, and the mixture was allowed to stand for separation. The lower organic layer was evaporated and concentrated at 60 C, -0.08Mpa (G) to no fraction, and obtain the 2,2-fluorobenzo[d][1,3]dioxo-5-yl)methanol 25.7g, The purity of the gas was determined by gas chromatography to be 96% (0.131 mol, yield 77.7%, based on 5-bromo-2,2-difluorobenzodioxole)

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; Fuxin Da Deli Chemical Co., Ltd.; Nie Qiang; Zhang Jinsheng; Jiang Shan; Jia Yitong; (9 pag.)CN109503544; (2019); A;,
Bromide – Wikipedia,
bromide – Wiktionary

Application 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.

a) 2,2-Difluoro-5-(3-fluoro-4-nitrophenyl)-1 ,3-benzodioxoleA slurry of 5-bromo-2,2-difluoro-1 ,3-benzodioxole (1.23 g, 5.2 mmol), 4-N- BOC-amino-3-fluorophenylboronic acid (1.58 g, 6.2 mmol), [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium (II) dichloromethane adduct (0.131 g, 0.16mmol), and 2M aqueous sodium carbonate solution (7.8 mL, 15.6 mmol) in 1 ,4-dioxane (25.0 mL) was heated at reflux for 2.5 hours then cooled to ambient temperature. The reaction was dried over sodium sulfate then filtered and evaporated under reduced pressure to a residue. Purification by column chromatography on silica (0-65% gradient of ethyl acetate in hexanes) gave 1 ,1- dimethylethyl [4-(2,2-difluoro-1 ,3-benzodioxol-5-yl)-2-fluorophenyl]carbamate as a waxy white solid (54%).A solution of 1 ,1-dimethylethyl [4-(2,2-difluoro-1 ,3-benzodioxol-5-yl)-2- fluorophenyl]carbamate (0.992 g, 2.70 mmol) in 1 :1 trifluoroacetic acid and dichloromethane (20 mL) was stirred at ambient temperature for 1.5 hours then EPO evaporated under reduced pressure. The resulting residue was treated with glacial acetic acid (20.0 ml_) and sodium perborate tetrahydrate (2.08 g, 13.5 mmol) then heated at 75 2C for 3 hours. The reaction was cooled to ambient temperature then poured onto ice (120 g). After 1 hour, the slurry was filtered and the collected solids were rinsed with water then suction dried. Purification of the solids by silica chromatography (0 to 50% gradient of ethyl acetate in hexanes) gave the title compound (0.249 g, 31%) as a yellow solid. MS (ES) m/e 298 (M + H)+.

The synthetic route of 33070-32-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2006/113432; (2006); A2;,
Bromide – Wikipedia,
bromide – Wiktionary