background and overview[1]
4-fluoro-7-bromobenzofuran can be used as a pharmaceutical synthesis intermediate. if 4-fluoro-7-bromobenzofuran is inhaled, move the patient to fresh air; if skin contact occurs, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel unwell; if in case of eye contact, 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]
the preparation of 4-fluoro-7-bromobenzofuran is divided into the following two steps:
step 1: preparation of 1-bromo-2-(2,2-diethoxyethoxy)-4-fluorobenzene
combine 2-bromo-5-fluorophenol (0101-2) (1.73g, 9.06mmol, 1.0 equivalent) and 2-bromo-1,1-diethoxyethane (5.45ml, 36.42mmol, 4.0 equivalent) was dissolved in n,n-dimethylformamide (20 ml), then potassium carbonate (2.50 g, 18.12 mmol, 2.0 equivalent) was added. replace the air in the reaction system with nitrogen three times, and then react at 95°c for 8 hours. the reaction solution was diluted with water (100 ml), and then extracted with ethyl acetate (40 ml × 3). the extract was dried with anhydrous sodium sulfate, concentrated, and then purified by silica gel column chromatography (petroleum ether: ethyl acetate = 50:1 ) to obtain the colorless oily liquid product 1-bromo-2-(2,2-diethoxyethoxy)-4-fluorobenzene (2.78g, yield: 100%). lcms(esi): m/z307[m+1]+.
step 2: preparation of 4-fluoro-7-bromobenzofuran
add 1-bromo-2-(2,2-diethoxyethoxy)-4-fluorobenzene (0102-2) (2.75g, 8.95mmol, 1.0 equivalent) into the reaction flask. phosphoric acid (9.08g, 26.86mmol, 3.0 equivalent) and 1,2-dichloroethane (40ml) were heated to 83°c for 3 hours. the reaction solution was cooled to room temperature and then washed with water (30 ml × 2). the organic layer was dried over anhydrous sodium sulfate, concentrated, and then purified by silica gel column chromatography (petroleum ether) to obtain the light yellow solid product 4-fluoro-7-bromobenzene. and furan (0.992g, yield: 52%). lcms(esi): m/z215[m+1]+.
apply[1]
4-fluoro-7-bromobenzofuran can be used as a pharmaceutical synthesis intermediate. for example, prepare 1-(4-fluorobenzofuran-7-yl)ethan-1-one: dissolve 4-fluoro-7-bromobenzofuran (0103-2) (0.95g, 4.42mmol, 1.0 equivalent) in in anhydrous toluene (15 ml), use a dry ice acetone bath to cool to -78°c, then slowly add n-butyllithium (2.5m, 2.47ml, 6.19mmol, 1.4 equivalent) dropwise, and after the dropwise addition is completed, cool to -78°c. stir for 1.5 hours. n-methoxy-n-methylacetamide (1.17 ml, 11.05 mmol, 2.5 equivalents) was added dropwise and then slowly warmed to room temperature and stirred for 4 hours. saturated ammonium chloride solution (50 ml) was added to quench the reaction. the aqueous layer was extracted with ethyl acetate (30 ml × 3). the organic layers were combined, dried over anhydrous sodium sulfate, and concentrated. the obtained crude product was subjected to silica gel column chromatography ( petroleum ether: ethyl acetate = 30:1) was purified to obtain the light yellow solid product 1-(4-fluorobenzofuran-7-yl)ethan-1-one (0.28g, yield: 36%). lcms(esi): m/z179[m+1]+.
main reference materials
[1](cn108658908) 1,3-disubstituted enone compounds and their applications
