* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With bromine; In water; at 25 - 85℃; for 9h;Reflux;
2, 2-difluoro-l, 3-benzodioxole (200g, 1.27mol) and water (456g, 25.3mol) were placed in a 1000 mL round -bottomed flask fitted with a mechanical stirrer, reflux condenser and pressure equalizing addition funnel. Bromine (284g, 1.77mol) was added drop-wise at 25C for one hour. During addition, the temperature of the mass was raised from 25C to 85C. The temperature of the reaction mass was maintained at 85C for 8 hours. The progress of the reaction was monitored by liquid chromatography. The temperature of the reaction mass was brought down to 25C. The layers were separated, the organic layer was washed with sodium bisulphite solution followed by sodium bicarbonate solutionto obtain the title compound. The crude mass was purified by vacuum distillation. Yield (%) : 80 Purity (%) : 99.8 (by liquid chromatography)
75%
With bromine; iron; at 20 - 30℃;Inert atmosphere; Large scale;
250.0 kg (1.581 kmol) of <strong>[1583-59-1]2,2-difluorobenzodioxole</strong> was placed in a 500 L lined PTFE enamel kettle, and 25.0 kg of iron filings were added under stirring, and the inside of the kettle was replaced with nitrogen. The reaction temperature was controlled at 20 to 30 C, and 250.0 kg (1.564 kmol) of bromine was added dropwise over 8 to 10 hours, and the tail gas was absorbed by liquid alkali. After the completion of the reaction, the reaction system was pumped into another 2000 L reaction vessel containing 1000 kg of cold water, and the temperature was controlled to 30 C or lower. The reaction was quenched by dropwise addition of 100 kg of 25% sodium hydrogen sulfite solution, and the pH of the system was adjusted to 8-9 by dropwise addition of 32% liquid alkali. The temperature was raised to 100 C and the product was distilled off by steam distillation. Approximately 310 kg of a crude 5-bromo-2,2-difluoropipepene ring was obtained, and further separated to obtain a 5-bromo-<strong>[1583-59-1]2,2-difluorobenzodioxole</strong> 250 kg (1.181 kmol), a purity of 99%, and a yield of 75%.
538 g
With hydrogen bromide; dihydrogen peroxide; at 10 - 70℃;
Example 1Process of preparation of 5-bromo-<strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> A mixture of 2,2-difluoro-l ,3-benzodioxote (560 g) and Hydrogen bromide(l 100 g, Assay 47%) were taken in a reaction vessel fitted with cold condenser. The reaction mixture was cooled to 10C and 30 % Hydrogen Peroxide solution (806 g) was added slowly in lot wise. Upon completion of addition, the temperature of the reaction mixture was cautiously raised to 70C. The organic layer was separated and washed with 20 % of sodium metabisulfite and then washed with 20% of potassium bicarbonate solution. The organic layer was dried over magnesium sulfate and filtered. The filtrate was distilled under high vacuum to obtain the title compound. Yield: 538 g
Step A Preparation of 5-bromo-2,2-difluoro- 1,3-benzodioxole Iron powder (2.8 g, 50 mmol) was added to a solution of <strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> (15.8 g, 100 mmol) in carbon tetrachloride (200 mL) at 0 C. under a nitrogen atmosphere. Bromine (5.2 mL, 100 mmol) was then added to the mixture dropwise over 15 min. The reaction was heated to reflux for 1 h and then stirred at room temperature overnight. The mixture was filtered through Celite and the filtrate was washed with 0.1N sodium thiosulfate solution. The organic layer was then dried (MgSO4), filtered, and concentrated under reduced pressure to afford the title compound of Step A as an oil (15.2 g, 64%). 1 H NMR (CDCl3): delta6.96 (m, 1H), 7.22 (m,2H).
With bromine; In tetrachloromethane; water;
Step C: Synthesis of 5-bromo-<strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> as an intermediate A mixture of 15.8 grams (0.1 mole) of <strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong> in 200 mL of carbon tetrachloride was stirred, and 2.8 grams (0.05 mole) of iron powder was added. The reaction mixture was cooled to 0 C., and 5.2 mL (0.1 mole) of bromine was added during a 20 minute period. Upon completion of addition the reaction mixture was cautiously warmed to 75 C. where it was stirred for one hour and then was allowed to cool to ambient temperature where it was stirred for 18 hours. The reaction mixture was taken up in 200 mL water and stirred for 20 minutes. The organic layer was separated and washed with water and then with two portions of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was distilled under high vacuum to yield 11.7 grams of 5-bromo-<strong>[1583-59-1]2,2-difluoro-1,3-benzodioxole</strong>. The nmr spectrum was consistent with the proposed structure.
With tetrabutylammomium bromide; palladium diacetate; sodium carbonate; In water; at 150℃; for 0.0833333h;Microwave irradiation; Sealed vessel;
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.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
