Isopropanol → 2'-Fluoro-4'-methylbiphenyl-2-carboxylic acid t-butyl ester

Temperature

90 °C

Compound A (22.8 g, 88.6 mmol) and 2-fluoro-4-methylphenylboronic acid (15.0 g, 97.4 mmol) were suspended in isopropyl alcohol (75 mL, 980 mmol). A solution of sodium carbonate (16 g, 150 mmol) in water (75 mL, 4.2 mol) was added and the mixture was degassed under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (1.0 g, 880 μmol) was then added and the mixture was stirred at 90° C. overnight. The mixture was cooled to room temperature, EtOAc (200 mL) and water (200 mL) were added, and the mixture was filtered. The liquor was extracted with EtOAc (2×100 mL), washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The material was purified by flash chromatography (0-15% EtOAc in hexanes) to yield compound B as a colorless oil (14.9 g, 96% purity).

1. customthe mixture was degassed under nitrogen
2. temperatureThe mixture was cooled to room temperature
3. filtrationthe mixture was filtered
4. extractionThe liquor was extracted with EtOAc (2×100 mL)
5. washwashed with saturated aqueous NaCl
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe material was purified by flash chromatography (0-15% EtOAc in hexanes)

ORD record

ord-fc8a62447cb34d688a8c1ad4d497ae45

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362061B2