Hydrochloric Acid → [2-Fluoro-3-(pyridin-4-yl)phenyl]boronic acid

Temperature

-78 °C

A cooled (−78° C.) solution of n-butyllithium (15.2 ml of a 2.5 M solution in hexanes, 38.0 mmol) in tetrahydrofuran (100 ml) was treated with 2,2,6,6-tetramethylpiperidine (6.69 ml, 39.8 mmol) and stirring at −78° C. was continued for 15 min. The reaction was then treated with a cooled (0° C.) solution of 4-(2-fluorophenyl)pyridine (6.26 g, 36.1 mmol) in tetrahydrofuran (20 ml) added dropwise over 10 min. This mixture was stirred at −78° C. for 2 h and then treated with trimethyl borate (8.16 ml, 72.3 mmol) added dropwise over 5 min. The reaction was stirred at −78° C. for 10 min then allowed to warm to ambient temperature. Next, 2 N hydrochloric acid (10 ml) was added and the mixture stirred for 30 min, then evaporated to dryness. The residue was stirred with 2 N hydrochloric acid (100 ml) for 1 h and then taken to pH 14 with 2 N sodium hydroxide (ca. 150 ml). This was washed with diethyl ether and the aqueous layer was cooled to 0° C. and adjusted to pH 8 with 36% hydrochloric acid. After stirring at 0° C. for 1 h the resulting solid was collected by filtration and dried to afford 5.20 g (66%) of 2-fluoro-3-(pyridin-4-yl)benzeneboronic acid as a white solid: MS (ES+) m/z 218 [M+H]+.

1. additionThe reaction was then treated with
2. additionadded dropwise over 10 min
3. stirringThis mixture was stirred at −78° C. for 2 h
4. additionadded dropwise over 5 min
5. stirringThe reaction was stirred at −78° C. for 10 min
6. temperatureto warm to ambient temperature
7. stirringthe mixture stirred for 30 min
8. customevaporated to dryness
9. stirringThe residue was stirred with 2 N hydrochloric acid (100 ml) for 1 h
10. washThis was washed with diethyl ether
11. temperaturethe aqueous layer was cooled to 0° C.
12. stirringAfter stirring at 0° C. for 1 h the resulting solid
13. filtrationwas collected by filtration
14. customdried

ORD record

ord-36fb26ed2b504d42b17f5dc14c529f1d

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936608B2