Triisopropyl borate → (4-Fluoro-3-methylphenyl)boronic acid

Temperature

-78 °C

5-Bromo-2-fluorotoluene (6 g, 31.7 mmol) was dissolved in dry THF (50 mL) and cooled to −78 C. under N2. n-BuLi (14 mL, 2.5M solution in THF) was added slowly using a dry syringe. Cloudiness appeared. The reaction was stirred for 40 minutes at −78° C. Triisopropyl borate (22 mL, 95 mmol) was slowly added while stirring. The reaction was allowed to warm to room temperature. Stirring continued for an additional 2 hours. A pale yellow, cloudy solution formed. (TLC (1:2 ethyl acetate/hexanes)) indicated disappearance of the starting material. The reaction was quenched by adding 10% aqueous NaOH (200 mL). After stirring for 45 minutes, 10% citric acid solution (300 mL) was added until, pH ˜5.0. The product was extracted with ethyl acetate (500 mL). The organic phase was washed with brine and dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure to provide an off white solid (yield: 4.1 g, 84%).

1. temperaturecooled to −78 C
2. stirringwhile stirring
3. temperatureto warm to room temperature
4. stirringStirring
5. waitcontinued for an additional 2 hours
6. customA pale yellow, cloudy solution formed
7. customThe reaction was quenched
8. additionby adding 10% aqueous NaOH (200 mL)
9. stirringAfter stirring for 45 minutes
10. addition10% citric acid solution (300 mL) was added until, pH ˜5.0
11. extractionThe product was extracted with ethyl acetate (500 mL)
12. washThe organic phase was washed with brine
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-c9751f6feb9e4e6fbf9998ef9fbbfb98

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07001895B2