Category: 33070-32-5

Application 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.

Step 1: A mixture of 5-bromo-2,2-difluoro-1,3-benzodioxole (15.0 g, 63.6 mmol), ethyl cyanoacetate (14.4 g, 127 mmol) and Na3PO4 (31.2 g, 191 mmol) in toluene (180 mL) was degassed three times and back filled with N2. Then Pd(dba)2 (1.46 g, 2.54 mmol) and PtBu3 (10% w/w in hexane, 10.3 g, 5.08 mmol) were added. H20 (0.9 mL) was added and the mixture was degassed three times and back filled with N2. The mixture was heated at 90C for 18 hours. The mixture was diluted with EtOAc (200 mL) and filtered. The filtrate was washed with H20 (100 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated to give 17 g of crude ethyl 2-cyano-2-(2,2-difluorobenzo[d][1,3]dioxol-5- yl)acetate as a black oil, which was used directly for the next step.

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; N30 PHARMACEUTICALS, INC.; SUN, Xicheng; QIU, Jian; STOUT, Adam; WO2014/186704; (2014); A2;,
Bromide – Wikipedia,
bromide – Wiktionary

33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, 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. Recommanded Product: 5-Bromo-2,2-difluorobenzodioxole

Preparation 33 5-Bromo-2,2-difluoro-4-methoxybenzo[d][1,3]dioxole A solution of LDA was prepared from diisopropylamine (4.2 g, 41 mmol) and n-BuLi (2.5 M; 15.4 mL, 38 mmol) in dry tetrahydrofuran (100 mL). The solution was cooled to -70 C. and treated in portions with 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (7.0 g, 30 mmol). After 2 h at -70 C., trimethylborate (4.3 g, 41 mmol) was added in portions, stirred at -70 C. for 1.5 h and then allowed to warm to ambient overnight. The mixture was cooled to -30 to -40 C. and treated carefully with 28% peracetic acid. The mixture was stirred for 30 min at -30 C., warmed to 5-10 C., treated with 10% NaHSO3 (100 mL) solution and stirred for 20 min. The mixture was acidified by addition of 6 M HCl and diluted with saturated NaCl solution (75 mL). The mixture was extracted ethyl acetate (2*100 mL) and the combined extracts were washed with saturated NaCl (50 mL), dried (Na2SO4) and rotary evaporated. The crude phenol was dissolved in dry DMSO (50 mL), treated with 95% NaH (750 mg, 30 mmol) and stirred for 30 min to produce a clear solution. Methyl iodide (5.0 g, 35 mmol) was added in portions, and the mixture was stirred for 20 h at 20 C. An additional 200 mg NaH were added and stirring was continued for 1 h more. The mixture was poured into water (100 mL) and extracted diethyl ether (2*75 mL). The combined extracts were washed with water (2*20 mL), with saturated NaCl (20 mL), dried (Na2SO4) and evaporated. The crude material was purified by chromatography on silica with a 0-20% ethyl acetate-hexane gradient to afford the title compound as a clear liquid (2.5 g, 31%): 1H NMR (400 MHz, CDCl3) delta 7.25 (d, J=8.5 Hz, 1H), 6.63 (d, J=8.5 Hz, 1H), 4.13 (s, 3H); 19F NMR (376 MHz, CDCl3) delta -49.66; EIMS m/z 266.

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

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. 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, This compound has unique chemical properties. The synthetic route is as follows., Quality Control of 5-Bromo-2,2-difluorobenzodioxole

General procedure: Method A. A solution of Pd(OAc)2 (25.2 mg, 0.112 mmol) and triphenylphosphine (147 mg, 0.560 mmol) in absolute ethanol (4 mL) and anhydrous toluene (4 mL) was stirred at RT under nitrogen for 10 min. After that period, commercially available 5-chloro-2-nitrotoluene 4 (646 mg, 3.76 mmol), 4 mL of 2M aqueous Na2CO3, and the appropriate boronic acid R1B(OH)2 (6.03 mmol) were sequentially added. The resulting mixture was heated at 100 C in a sealed vial under nitrogen overnight. After being cooled to RT, the mixture was diluted with water and extracted with EtOAc. The combined organic phase were dried and concentrated. The crude product was purified by flash chromatography over silica gel column using n-Hex/EtOAc or CHCl3/MeOH mixtures as the eluent.

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 33070-32-5.

Reference:
Article; Granchi, Carlotta; Roy, Sarabindu; De Simone, Alessio; Salvetti, Irene; Tuccinardi, Tiziano; Martinelli, Adriano; MacChia, Marco; Lanza, Mario; Betti, Laura; Giannaccini, Gino; Lucacchini, Antonio; Giovannetti, Elisa; Sciarrillo, Rocco; Peters, Godefridus J.; Minutolo, Filippo; European Journal of Medicinal Chemistry; vol. 46; 11; (2011); p. 5398 – 5407;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, molecular formula is C7H3BrF2O2, 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. Formula: C7H3BrF2O2

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 was stirred at 100 C. overnight (16 hours). The reaction mixture was cooled to ambient temperature, and partitioned between ethyl acetate and aqueous 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 temperature 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 provide the title compound. 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)-.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 33070-32-5, its application will become more common.

Reference:
Patent; AbbVie S.a.r.l.; Galapagos NV; Altenbach, Robert J.; Bogdan, Andrew; Desroy, Nicolas; Gfesser, Gregory A.; Greszler, Stephen N.; Kym, Philip R.; Liu, Bo; Malagu, Karine Fabienne; Merayo Merayo, Nuria; Pizzonero, Mathieu Rafael; Searle, Xenia B.; Van der Plas, Steven Emiel; Wang, Xueqing; Yeung, Ming C.; Zhao, Gang; (101 pag.)US2018/244640; (2018); A1;,
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. 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, This compound has unique chemical properties. The synthetic route is as follows., Recommanded Product: 33070-32-5

Example 35A ethyl 4-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)butanoate To a solution of 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (9.9 g, 41.8 mmol) in tetrahydrofuran (40 mL) was added 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos, 0.343 g, 0.835 mmol) and palladium(II) acetate (0.094 g, 0.418 mmol). A 0.5 M solution of 4-ethoxy-4-oxobutylzinc bromide in tetrahydrofuran (100 mL, 50.1 mmol) was added to the reaction mixture at ambient temperature under nitrogen over 15 minutes. A slight exotherm from 22 C. to 42 C. was noted. The reaction mixture was stirred at ambient temperature for 1 hour. The reaction mixture was partitioned between ethyl acetate and 1 N HCl solution. The organic fraction was separated, washed by brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using a 220 g silica gel cartridge eluted with 0-10% tert-butyl methyl ether/heptanes to give the title compound (8.96 g, 79% yield). 1H NMR (400 MHz, CDCl3) delta ppm 1.28 (t, J=7.1 Hz, 3H), 1.95 (p, J=7.5 Hz, 2H), 2.33 (t, J=7.4 Hz, 2H), 2.67 (t, J=7.6 Hz, 2H), 4.16 (q, J=7.1 Hz, 2H), 6.84-6.95 (m, 2H), 6.98 (d, J=8.1 Hz, 1H).

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 33070-32-5.

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

33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, 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: 5-Bromo-2,2-difluorobenzodioxole

Example 1 : 3-(2,2-Difluoro-benzo[1 ,31dioxol-5-ylmethyl)-piperidine-1 -carboxylic acid pyridin-3-ylannide.Step A: 3-(2,2-Difluoro-benzo[1.SIdioxol-delta-ylnnethvD-piperidine-i-carboxylic acid tert-butyl ester.; 1 -Boc-3-methylene piperidine (842 mg, 4.27 mmol) was degassed (neat) for 15 minutes and then treated with a THF solution of 9-BBN (0.5 M in THF, 8.6 ml_, 4.3 mmol). The reaction mixture was refluxed for 2 h, then cooled to rt. The reaction mixture was then added, via cannula, to a preformed solution of 5-bromo-2,2-difluoro-1 ,3-benzodioxole (1.00 g, 4.22 mmol), Pd(dppf)CI2?CH2CI2 (94 mg, 0.128 mmol), and potassium carbonate (746 mg, 5.40 mmol) in DMF/H2O (10 mL/1 ml_). The resultant mixture was heated at 60 0C for 18 h, cooled to rt, poured into water, basified to pH 11 with 1 N NaOH, and extracted with EtOAc (3x). The organic layers were combined, dried (Na2SO4), and concentrated. The crude residue was purified (FCC) to give 3-(2,2-difluoro-benzo[1 ,3]dioxol-5-ylmethyl)- piperidine-1 -carboxylic acid tert-butyl ester (1.00 g, 67%).

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

Reference:
Patent; JANSSEN PHARMACEUTICA NV; BREITENBUCHER, J., Guy; KEITH, John, M.; TICHENOR, Mark, S.; CHAMBERS, Alison, L.; JONES, William, M.; HAWRYLUK, Natalie, A.; TIMMONS, Amy, K.; MERIT, Jeffrey, E.; SEIERSTAD, Mark, J.; WO2010/68452; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Electric Literature of 33070-32-5, 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. 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, This compound has unique chemical properties. The synthetic route is as follows.

Preparation 29 4-(2,2-difluoro-13-benzodioxol-5-yl)-2-fluoroaniline A solution of 5-bromo-2,2-difluoro-1,3-benzodioxole (1.73 mmol), bis(pinacolato)diboron (1.90 mmol), potassium acetate (5.20 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)¡¤dichloromethane adduct (0.32 mmol) in N,N-dimethylformamide (8.0 mL) was heated at 80 C. for 2 h. The reaction mixture was cooled and was treated with 2-fluoro-4-iodoaniline (0.86 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)¡¤dichloromethane adduct (0.32 mmol), cesium carbonate (8.65 mmol), and water (2.0 mL). The reaction mixture was then heated at 100 C. for 18 h. The reaction mixture was cooled, poured into brine (60 mL), and extracted with (3*50 mL) ethyl acetate. The combined organic layers were dried over magnesium sulfate and decolorizing charcoal, filtered through Celite, and concentrated in vacuo. Purification of the residue by Gilson reverse phase HPLC and neutralization of the collected fractions afforded the title product as a tan solid (70%). ESMS [M+H]+: 267.8.

The chemical industry reduces the impact on the environment during synthesis 5-Bromo-2,2-difluorobenzodioxole. I believe this compound will play a more active role in future production and life.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; CYTOKINETICS; US2007/259951; (2007); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Application of 33070-32-5, The chemical industry reduces the impact on the environment during synthesis 33070-32-5, name is 5-Bromo-2,2-difluorobenzodioxole, I believe this compound will play a more active role in future production and life.

A solution of 5-bromo-2,2-difluoro-1 ,3-benzodioxole (1.73 mmol), bis(pinacolato)diboron (1.90 mmol), potassium acetate (5.20 mmol), and dichloro[1 ,1′- bis(diphenylphosphino)ferrocene]palladium(ll)?dichloromethane adduct (0.32 mmol) in Lambda/,Lambda/-dimethylformamide (8.0 ml_) was heated at 80 0C for 2 h. The reaction mixture was cooled and was treated with 2-fluoro-4-iodoaniline (0.86 mmol), dichloro[1 ,1 ‘- bis(diphenylphosphino)ferrocene]palladium(ll)?dichloromethane adduct (0.32 mmol), cesium carbonate (8.65 mmol), and water (2.0 mL). The reaction mixture was then heated at 100 0C for 18 h. The reaction mixture was cooled, poured into brine (60 mL), and extracted with (3 x 50 ml.) ethyl acetate. The combined organic layers were dried over magnesium sulfate and decolorizing charcoal, filtered through Celite, and concentrated in vacuo. Purification of the residue by Gilson reverse phase HPLC and neutralization of the collected fractions afforded the title product as a tan solid (70%). ESMS [M+H]+: 267.8.

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, 5-Bromo-2,2-difluorobenzodioxole, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; CYTOKINETICS; WO2006/20358; (2006); A2;,
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., HPLC of Formula: C7H3BrF2O2

To a cold solution of 5-bromo-2,2-difluorobenzo[dl[1,3ldioxole (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 inthe 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% H2504 solution (50 mL) was added slowlywhich 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 NaHCO3 solution. The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in 100 mL of tert-butyl methyl ether and cooled to 0 C. 30% Hydrogen peroxide solution in water (5.39 mL, 52.7 mmol) wasadded 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. ?H NMR(400 MHz, DMSO-d6) oe ppm 9.75 (s, 1H), 7.12 (d, J = 8.7 Hz, 1H), 6.75 (d, J = 2.4 Hz, 1H),6.52 (dd, J = 8.7, 2.5 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; CALICO LIFE SCIENCES LLC; ABBVIE INC.; MARTIN, Kathleen, Ann; SIDRAUSKI, Carmela; PLIUSHCHEV, Marina, A.; TONG, Yunsong; XU, Xiangdong; ZHANG, Qingwei, I.; SWEIS, Ramzi, Farah; DART, Michael, J.; (184 pag.)WO2019/90078; (2019); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

33070-32-5, 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.

Step 1: Pre [00383] To a stirring solution of tert-butyllithium (1.76 mL, 3.0 mmol, 2.0 equiv, 1.7 M in pentane) at -78 C was added dropwise a solution of 5-bromo-2,2-difluorobenzo-[l ,3]- dioxole (355 mg, 1.5 mmol, 1.0 equiv) in THF (5 mL). After 30 min, ethyl formate (44 mg, 0.5 mmol, 0.33 equiv) in THF (1 mL) was added. The mixture was stirred at -78 C for 1 h and subsequently warmed to room temperature and stirred for an additional 4 h. The reaction mixture was quenched by the addition of a saturated solution of NH4C1 and extracted with EtOAc (3x). The organic layers were combined, dried over a2S04, and concentrated under reduced pressure. Purification of the crude oil by flash chromatography (15% EtOAc/hexanes) provided bis(2,2-difluorobenzo[d][l,3]dioxol-5-yl)methanol as an off-white solid (196 mg, 92%): ‘H NMR (400 MHz, CDC13) delta 7.09 (d, J= 1.61 Hz, 2H), 7.07 (dd, J= 1.74, 8.18 Hz, 2H), 7.02 (d, J= 8.15 Hz, 2H), 5.81 (d, J= 3.03 Hz, 1H), 2.28 (d, J= 3.27 Hz, 1H).

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; ABIDE THERAPEUTICS; THE SCRIPPS RESEARCH INSTITUTE; CISAR, Justin, S.; GRICE, Cheryl, A.; JONES, Todd, K.; WANG, Dong-Hui; WEBER, Olivia; CRAVATT, Benjamin, F.; NIPHAKIS, Micah, J.; COGNETTA, Armand; CHANG, Jae Won; WO2013/142307; (2013); A1;,
Bromide – Wikipedia,
bromide – Wiktionary