Trimethyl borate → 4-Hexylphenylboronic Acid

Temperature

-78 °C

To a solution of 4-bromo-1-hexylbenzene (500 mg, 1.7 mmol) in THF (15 mL) at −78° C. was added t-butyllithium (1.7 M in pentane, 2.0 mL) slowly dropwise. After stirring at −78° C. for 1 h, trimethyl borate (0.39 mL, 3.46 mmol) was added. The reaction mixture was warmed at RT over 2 h. After stirring at RT for 15 min, the reaction mixture was quenched with saturated solution of ammonium chloride and extracted with ethyl acetate. The combined organic layers were washed with HCl (10% solution), brine, and dried (MgSO4), filtered, and concentrated under reduce pressure to give 415 mg (4-hexylphenyl)boronic acid as a colorless solid. A solution of the resulting boronic acid (962 mg, 4.07 mmol) and Intermediate 3 (1.1 g, 4.27 mmol) in toluene (37 mL), methanol (1.2 mL) and water (2 mL) were added potassium carbonate (1.09 g, 8.45 mmol) and LiCl (181 mg, 4.27 mmol) with stirring. After bubbling with Ar for 10 min, tetrakis(triphenylphosphine)palladium(0) (99 mg) was added and heated at 95° C. for 16 h. After the reaction mixture was cooled at RT, it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, and dried (MgSO4), filtered, and concentrated under reduce pressure. The residue was purified by MPLC (15% ethyl acetate in hexanes) gave 1.16 g of Intermediate 6 as colorless solid.

1. temperatureThe reaction mixture was warmed at RT over 2 h
2. stirringAfter stirring at RT for 15 min
3. customthe reaction mixture was quenched with saturated solution of ammonium chloride
4. extractionextracted with ethyl acetate
5. washThe combined organic layers were washed with HCl (10% solution), brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-8cd4f59adb714d3a81ff1f62153cbff6

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716267B2