background and overview[1]
2-chloro-4-bromo-5-fluorotoluene can be used as a pharmaceutical synthesis intermediate. if you inhale 2-chloro-4-bromo-5-fluorotoluene, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable. ; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
preparation [1-2]
2-chloro-4-bromo-5-fluorotoluene can be used as a pharmaceutical synthesis intermediate if the following reaction occurs:
the specific steps are: add a mixture of 2-chloro-4-bromo-5-fluorotoluene (5.0g, 23mmol), copper(i) cyanide (4.0g, 45mmol) and copper(i) iodide (8.6 g, 45 mmol) was dissolved in nmp (50 ml) and heated at 140°c overnight. after cooling to room temperature, the mixture was filtered, the filtrate was diluted with water (100 ml), and extracted with ethyl acetate (100 ml × 3). the combined organic layers were washed with water (100 ml) and dried over naso. the solvent was removed and the residue was purified by sgc (eluting with petroleum ether/etoac = 10/1) to give 5-chloro-2-fluoro-4-methylbenzonitrile (1.7 g, 45% yield) as white solid.
in addition, 2-chloro-4-bromo-5-fluorotoluene can also undergo the following reactions:
the specific steps are: combine 2-chloro-4-bromo-5-fluorotoluene (10.0g, 44.75mmol, 1.0 equivalent), nbs (7.9g, 44.75mmol, 1.0 equivalent) and aibn (736mg, 4.48mmol) the mixture was heated to reflux in 0.1 l eq. ccl (250 ml) and stirred under n2 for 3 h. concentrate the mixture. the residue was purified by column chromatography (pe-pe/ea = 30/1, v/v) to give 1-bromo-4-bromomethyl-5-chloro-2-fluoro-benzene (7.5 g, 56%), it is oily.
main reference materials
[1] us20160009667 substituted benzoxazoles and methods of use thereof
[2] wo2015103317 therapeutic inhibitory compounds
