Water → 5-Bromo-2-isobutoxybenzonitrile

Temperature

25 °C

After cooling a suspension of sodium hydride (1.64 g, 60% suspension in mineral oil, 37.5 mmol) in N,N-dimethylformamide (50 mL) to 0° C., 2-methyl-1-propanol (3.47 mL, 37.5 mmol) was added stepwise. And the reaction mixture was stirred at 25° C. for 20 minutes. Again, the reaction mixture was cooled to 0° C., 2-fluoro-5-bromobenzonitrile (5.00 g, 25.0 mmol) was added stepwise to the reaction mixture and the mixture was stirred at 25° C. for 15 hours. After the completion of the reaction, water (100 mL) was added and the mixture was extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with saturated brine (2×50 mL), and dried over sodium sulfate anhydrous. After removing sodium sulfate by filtration, the solvent was evaporated under reduced pressure, and the resulting crude compound was purified on silica-gel chromatography (hexane/ethyl acetate=9/1) to obtain the titled compound (6.04 g). Yield: 95%.

1. temperatureAfter cooling
2. temperatureAgain, the reaction mixture was cooled to 0° C.
3. stirringthe mixture was stirred at 25° C. for 15 hours
4. additionwas added
5. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
6. washThe combined organic layer was washed with saturated brine (2×50 mL)
7. dry with materialdried over sodium sulfate anhydrous
8. customAfter removing sodium sulfate
9. filtrationby filtration
10. customthe solvent was evaporated under reduced pressure
11. customthe resulting crude compound was purified on silica-gel chromatography (hexane/ethyl acetate=9/1)

ORD record

ord-3a878717b5ab4e99a69a056f82d71e52

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916714B2