Diisopropylamine → 2-Fluoro-5-methylpyridine-3-boronic acid

Temperature

-78 °C

n-Butyllithium (2.5M solution in hexane, 9.6 mL, 24 mmol) was added to a mixture of diisopropylamine (3.4 mL, 24 mmol) in THF (5.00 mL, 61 mmol) at 0° C. and the resulting pale yellow solution was stirred at the same temperature for 30 min and then cooled down to −78° C. A suspension of 2-fluoro-5-methylpyridine (Aldrich, St. Louis, Mo.) (2.22 g, 20 mmol) in THF (5.00 mL, not complete dissolved) was slowly added. The resulting bright yellow solution was stirred at −78° C. for 1 h, treated with a solution of tri-i-propylborate (6.9 mL, 30 mmol) in THF (10.00 mL) and then allowed to warm up to room temperature. The yellow suspension was quenched with 1 N NaOH until basic (pH about 10) and the organic layer was separated. The aqueous layer was collected and carefully acidified with 6 N aqueous HCl until slightly acidic, and then extracted with EtOAc (×3). The combined organic layers were dried (Na2SO4), filtered and concentrated. The resulting white solid was washed with ether to give 2-fluoro-5-methylpyridin-3-ylboronic acid (2.9196 g, 94% yield) as a white solid. LCMS (API-ES) m/z 156 (M+H)+.

1. dissolutionnot complete dissolved)
2. additionwas slowly added
3. stirringThe resulting bright yellow solution was stirred at −78° C. for 1 h
4. temperatureto warm up to room temperature
5. customThe yellow suspension was quenched with 1 N NaOH until basic (pH about 10)
6. customthe organic layer was separated
7. customThe aqueous layer was collected
8. extractionthen extracted with EtOAc (×3)
9. dry with materialThe combined organic layers were dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. washThe resulting white solid was washed with ether

ORD record

ord-836c61a53c534fa1bb5bab4ee9f45c16

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2