Hexane → 2-(Trifluoromethyl)pyridine-4-boronic acid

Temperatur

-78 °C

To a solution of 4-iodo-2-(trifluoromethyl)pyridine [purchased from Matrix Scientific] (2.5 g, 9.16 mmol) and triisopropylborate (2.54 mL, 10.99 mmol) in anhydrous tetrahydrofuran (20 mL) at −78° C. under nitrogen was added dropwise a solution of n-butyl lithium in hexane (2.5 M, 4.03 mL, 10.07 mmol). The reaction was stirred at −78° C. for 2½ hours then allowed to warm slowly to −10° C. over 1 hour. The reaction mixture was then quenched by the addition of water (20 mL) and the tetrahydrofuran removed under reduced pressure. The resulting aqueous phase was diluted with water (40 mL) and washed with ether (2×40 mL). The aqueous phase was then acidified to pH 5 by the addition of acetic acid and the resulting oily suspension extracted with ether (100 mL). The organic phase was separated, washed with saturated brine (2×50 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give an off-white foam. Ether (12 mL) and hexanes (24 mL) were added and the resulting suspension stirred vigorously for 30 minutes then filtered to give 2-(trifluoromethyl)pyridine-4-boronic acid (1.163 g, 67% yield) as a cream solid.

1. temperatureto warm slowly to −10° C. over 1 hour
2. customThe reaction mixture was then quenched by the addition of water (20 mL)
3. customthe tetrahydrofuran removed under reduced pressure
4. additionThe resulting aqueous phase was diluted with water (40 mL)
5. washwashed with ether (2×40 mL)
6. additionThe aqueous phase was then acidified to pH 5 by the addition of acetic acid
7. extractionthe resulting oily suspension extracted with ether (100 mL)
8. customThe organic phase was separated
9. washwashed with saturated brine (2×50 mL)
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customto give an off-white foam
14. stirringthe resulting suspension stirred vigorously for 30 minutes
15. filtrationthen filtered

ORD-Eintrag

ord-fc7dc5f8f23c42f397a5be3d3cb96aa9

Quelldatensatz

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09409893B2