Dimethylformamide → 3-Bromo-5-fluorobenzonitrile

A 250-mL round-bottom flask equipped with a magnetic stir bar was charged with 1,3-dibromo-5-fluorobenzene (7.70 g, 30.3 mmol), DMF (45 mL), pyridine (4.9 mL), and copper (I) cyanide (2.72 g, 30.3 mmol) under nitrogen. A reflux condenser was attached to the flask. The green, cloudy mixture was stirred at reflux for 3 h. Once lower Rf impurities were observed, the reaction was allowed to cool to room temperature. The reaction was quenched with 30 mL of ether, and a precipitate formed in the dark solution. The precipitate was gravity-filtered though Celite. The filtrate was rinsed three times with ether (100 mL/50 g bromide). The isolated solution was added to a separatory funnel. The organic layer was washed with a 2:1 mixture of water and concentrated ammonium hydroxide (30 mL), followed by saturated ammonium chloride solution (2×30 mL) and saturated sodium bicarbonate (30 mL). The aqueous layers were extracted with ether (3×40 mL). The organic layers were combined and dried over anhydrous sodium sulfate. The product was purified by flash column chomatography to yield 3-bromo-5-fluorobenzonitrile (2.10 g, 35%). 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.54-7.50 (m, 1H), 7.35-7.32 (m, 1H).

1. customA 250-mL round-bottom flask equipped with a magnetic stir bar
2. customA reflux condenser was attached to the flask
3. temperatureat reflux for 3 h
4. customThe reaction was quenched with 30 mL of ether
5. customa precipitate formed in the dark solution
6. filtrationThe precipitate was gravity-filtered though Celite
7. washThe filtrate was rinsed three times with ether (100 mL/50 g bromide)
8. additionThe isolated solution was added to a separatory funnel
9. washThe organic layer was washed with a 2:1 mixture of water and concentrated ammonium hydroxide (30 mL)
10. extractionThe aqueous layers were extracted with ether (3×40 mL)
11. dry with materialdried over anhydrous sodium sulfate
12. customThe product was purified by flash column chomatography

ORD record

ord-74c65f686bf744d49c439617bdd99fcc

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071588B2