Hexane → 2-Methylpyridine-5-boronic acid

Temperature

-78 °C

To a stirred solution of 5-bromo-2-methyl-pyridine (992 mg, 5.8 mmol) in diethyl ether (5 mL) was slowly added n-butyl lithium in hexane (1.4 M, 5 mL, 7 mmol) at −78° C. over a span of 10 minutes under nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 90 minutes. At this time, tri-isopropyl borate (1.30 g, 6.9 mmol) was slowly added, and the resulting mixture was allowed to warm to room temperature and stirred for an additional 90 minutes. The reaction was quenched with 5% aqueous sodium hydroxide solution (6 mL) at 0° C. and was extracted with diethyl ether (25 mL×4). The pH of the aqueous solution was adjusted to about 7 by the slow addition of 2N hydrochloric acid. The aqueous layer was extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-methyl-5-pyridinylbronic acid, which was used without further purification.

1. customat −78° C.
2. customover a span of 10 minutes
3. temperatureto warm to room temperature
4. stirringstirred for an additional 90 minutes
5. customThe reaction was quenched with 5% aqueous sodium hydroxide solution (6 mL) at 0° C.
6. extractionwas extracted with diethyl ether (25 mL×4)
7. additionThe pH of the aqueous solution was adjusted to about 7 by the slow addition of 2N hydrochloric acid
8. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×3)
9. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto give 2-methyl-5-pyridinylbronic acid, which
13. customwas used without further purification

ORD record

ord-97c6af484c504e788af850146de79abd

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163781B2