Hydrochloric Acid → (2-Cyano-4-fluorophenyl)boronic acid

2-Bromo-5-fluorobenzonitrile (6.00 g, 30.0 mmol) and triisopropyl borate (8.28 mL, 36.0 mmol) were dissolved in a mixture of toluene (48 mL) and tetrahydrofuran (12 mL), and the solution was cooled in a dry ice/acetone bath. A solution of n-butyllithium in hexanes (2.5M, 14.4 mL, 36.0 mmol) was added drop-wise over 1 hour, and the reaction was then allowed to warm to room temperature with stirring over 18 hours. The mixture was cooled in an ice bath and treated with a 2N aqueous hydrochloric acid solution until the pH reached 1, then allowed to warm to room temperature, at which time the layers were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed twice with water, once with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting solid was recrystallized from ethyl acetate-heptane to provide (2-cyano-4-fluorophenyl)boronic acid as a white solid. Yield: 2.20 g, 13.3 mmol, 44%. 1H NMR (400 MHz, CD3OD) δ 7.43 (ddd, J=8.6, 8.6, 2.5 Hz, 1H), 7.55 (dd, J=8.8, 2.5 Hz, 1H), 7.69 (br s, 1H).

1. temperaturethe solution was cooled in a dry ice/acetone bath
2. temperatureThe mixture was cooled in an ice bath
3. temperatureto warm to room temperature, at which time the layers
4. customwere separated
5. extractionthe aqueous layer was extracted twice with ethyl acetate
6. washThe combined organic layers were washed twice with water, once with saturated aqueous sodium chloride solution
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe resulting solid was recrystallized from ethyl acetate-heptane

ORD record

ord-571907dd8c7c4343b600ea51aff14f5c

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278457B2