Acetic Acid → 2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Temperature

-78 °C

A −78° C. solution of Example 68B (3.35 g, 15 mmol) diethyl ether (100 mL) was treated dropwise with 2.5 M n-butyllithium (7.2 mL, 18 mmol), stirred for 2 hours at −78° C., treated with tributyl borate (4.14 g, 18 mmol), stirred at −78° C. for one hour and warmed to room temperature over 2 hours. The solution was treated with pinacol (2.30 g, 19.5 mmol) and acetic acid (0.9 g, 15 mmol), stirred overnight, and filtered through diatomaceous earth (Celite®). The pad was washed with diethyl ether several times and the filtrate was concentrated to a volume of 50 mL. The mixture was diluted with ethyl acetate, washed with water and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel eluting with 25:1 hexanes/ethyl acetate to provide 2.34 g (70%) of the desired product. MS (DCI) m/e 224 (M+H)+; 1H NMR (300 MHz, CDCl3,) δ 8.24 (d, J=5.1 Hz, 1H), 7.50 (dd, J=4.8, 2.7 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 1.36 (s, 12H).

1. stirringstirred at −78° C. for one hour
2. temperaturewarmed to room temperature over 2 hours
3. stirringstirred overnight
4. filtrationfiltered through diatomaceous earth (Celite®)
5. washThe pad was washed with diethyl ether several times
6. concentrationthe filtrate was concentrated to a volume of 50 mL
7. additionThe mixture was diluted with ethyl acetate
8. washwashed with water and brine
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customThe residue was purified by flash column chromatography on silica gel eluting with 25:1 hexanes/ethyl acetate

ORD record

ord-d2e1541157414efdaed29ab348f82dd6

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456169B2