The synthetic route of 2-Bromo-5-fluoroaniline has been constantly updated, and we look forward to future research findings.
These common heterocyclic compound, 1003-99-2, name is 2-Bromo-5-fluoroaniline, 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. Quality Control of 2-Bromo-5-fluoroaniline
00299] To a 2-L reactor equipped with a mechanic agitator, a condenser, a thermocouple, a baffle, and nitrogen inlet were charged 228 g of water, 200 g of 2-bromo- 5-fluoroaniline and 80 g of 4-nitrophenol. To this mixture was charged 96percent sulfuric acid in 10-30 min at 20-1200C. The mixture was heated to 135-1400C and 194 g of glycerol was charged into the reactor over two hours at 135-145¡ãC. The mixture was held at 135- 145¡ãC for 1 hour after the addition. The reaction mixture was cooled to below 20-500C and slowly transferred to a 5-L reactor containing 1 100 g of water and 121O g of toluene. The 2-L reactor was washed with 300 g of water and the wash was combined into the 5-L- 101 -USlDOCS 6425925V I Docket No. AM 102651 (361 19.379WO1)reactor. The pH of the contents in the 5-L reactor was adjusted to pH 8-10 by adding approximately 1233 g (1370 mL) ammonium hydroxide (28-30 percent NH3) at 20-400C. The mixture was stirred at room temperature for 15 min and the solid by-product was filtered off while the filtrate was retained. The filter cake was washed with 400 ml of toluene and the all the filtrate was combined and charged a 3-L reactor. About 500 ml of 8.5percent KOH solution was charged into the 3-L reactor and stirred for 10 min and bottom aqueous layer was spit off. A second portion of 500 ml of 8.5percent KOH solution was added and the mixture was stirred for 15 min and the bottom aqueous layer was split off. Water 500 ml was added and stirred for 15 min before the bottom aqueous layer was split off. The organic layer was heated to distill off about 100-200 ml of toluene to azeo tropically remove water. A clear solution will be obtained. Typical yield 178g real 8-bromo~5- fluoroquinoline, -75percent.[00300] Alternatively, 8-bromo-5-fluoroquinoline was prepared by adding a warm mixture containing 2-bromo-5-fluoroaniline (10Og, 1.0 eq), 4-nitrophenol (4Og, 0.54 eq), and glycerol (97 g, 2.0 eq) over 1.5 hours to sulfuric acid (267 ml) and water (1 14 mL) at 140-1500C. The initial mixture showed 37.8percent 4-nitrophenol by relative HPLC areapercent. Samples showed 4.7percent 4-nitrophenol immediately after adding 50percent of mixed starting materials and 5.0percent immediately after adding all of the materials. The yield upon workup was 87.5percent, with total impurities 0.29percent. Addition of less (0.46 eq, 34 g) 4-nitrophenol also successfully produced the intermediate of interest at acceptable yield.
The synthetic route of 2-Bromo-5-fluoroaniline has been constantly updated, and we look forward to future research findings.
Reference:
Patent; WYETH; WO2008/67390; (2008); A2;,
Bromide – Wikipedia,
bromide – Wiktionary