[Lithium metaborate label: Title] Background and Overview
2-Chloro-3-bromo-4-iodopyridine can be used as a pharmaceutical synthesis intermediate. If 2-chloro-3-bromo-4-iodopyridine is inhaled, 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 unwell. ; 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 method of 2-chloro-3-bromo-4-iodopyridine
2-Chloro-3-bromo-4-iodopyridine was prepared as follows: To a 1.8 M solution of lithium diisopropylamide in THF (70 mL, 126 mmol) at -78°C under argon, 2-chloro – A solution of 3-bromopyridine (25 g, 126 mmol) in THF (100 μl nitropyridine). mL) over 2 hours. The resulting reaction mixture was stirred at -78 °C for 1 h, then a solution of I2 (32 g, 126 mmol) in 200 mL THF was added over 2 h. The reaction mixture was stirred at -78°C for 30 minutes. Brine (150 mL), then EtOAc (200 mL) was added to the reaction mixture and the layers were separated. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was passed through a bed of silica gel, eluting with 2% EtOAc/hexane, and 38.5 g of the product, a mixture of regioisomers, 2-chloro-3-bromo-4-iodopyridine, was isolated as a light brown solid. HPLC/MS: retention time = 3.073 and 3.151 minutes, [M+H]+=318.
Preparation method and application of 2-chloro-3-bromo-4-iodopyridine
Preparation of 3-bromo-2-chloro-4-(4-chlorophenyl)pyridine: At room temperature and argon, add crude 2-chloro-3-bromo-4-iodopyridine (10.0g, 31.41mmol ) to a solution of toluene (120mL), add 4-chlorophenylboronic acid (5.8g, 37.1mmol), tetrakis(triphenylphosphine)palladium (2.2g, 1.9mmol) and Na2CO3 (6:6g, 62.3mmol) in water (20mL) solution. The resulting suspension was stirred and heated at 100°C under argon for 2.5 hours. After the reaction mixture was cooled to room temperature, water (120 mL) and EtOAc (150 mL) were added. Layering. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel column, eluting with 7% ethyl acetate-hexane) to isolate 3.7 g of the title compound as a white solid. HPLC/MS: Retention time = 3.78 minutes, [M+H]+=302.1HNMR (CDCl3, 500MHz): δ8.35 (d, J=5.0Hz, 5H), 7.46 (d, J=10.0Hz, 2H) , 7.34 (d, J=10.0Hz, 2H), 7.14 (d, J=5.0Hz, 1H).
