Triisopropyl borate → 5-(1-(Tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridin-3-ylboronic acid

Temperature

-78 °C

n-Butyllithium (1.55M in hexane) (Aldrich, St. Louis, Mo.; 4.98 mL, 7.72 mmol) was added (dropwise over 5 min) to a solution of 5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridine (1.89 g, 7.01 mmol) in THF (35 mL) at −78° C., and the resulting yellow solution was stirred at −78° C. for 1 h. Triisopropyl borate (Aldrich, St. Louis, Mo.; 1.935 mL, 8.42 mmol) was then added, and the resulting mixture was stirred at −78° C. for 1 h. The reaction mixture was subsequently partitioned between EtOAc (250 mL) and water (90 mL) (1 N aq. HCl (12.0 mL) was added to bring the pH to about 6.5). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to provide 5-(1-(tert-butyldimethylsilyloxy)propan-2-yl)-2-fluoropyridin-3-ylboronic acid (2.25 g, 7.18 mmol, 102% yield) as a colorless oil, which was used directly in the subsequent step. m/z (ESI, +ve) 314.2 (M+H)+.

1. stirringthe resulting mixture was stirred at −78° C. for 1 h
2. customThe reaction mixture was subsequently partitioned between EtOAc (250 mL) and water (90 mL) (1 N aq. HCl (12.0 mL)
3. additionwas added
4. customThe organic layer was separated
5. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
6. dry with materialThe combined organic extracts were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-592c7a22ca0349f0b09cd3dea373095f

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2