Sodium Carbonate → Methyl 3-amino-2'-fluorobiphenyl-4-carboxylate

Temperatur

90 °C

Step 1 A mixture of methyl-2-amino-4-bromobenzoate (3.06 g, 13.3 mmol), 2-fluorophenylboronic acid (2.23 g, 16.0 mmol), tetrakis(triphenylphosphine)palladium (1.54 g, 1.33 mmol) and 1 M aqueous sodium carbonate (16.6 mL, 16.6 mmol) in 1,2-dimethoxyethane (66.5 mL) was stirred at 90° C. overnight. The mixture was cooled to rt, filtered through a pad of Celite and the solids were rinsed with EtOAc. The filtrate was washed with water and brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from hexane to 90:10 hexane-EtOAc) to provide methyl-3-amino-2′-fluorobiphenyl-4-carboxylate (2.63 g, 81%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 7.90 (d, J=8.25 Hz, 1H), 7.38-7.46 (m, 1H), 7.27-7.35 (m, 1H), 7.08-7.22 (m, 2H), 6.85 (s, 1H), 6.82 (d, J=8.25 Hz, 1H), 5.83 (br s, 1H), 3.88 (s, 3H). Mass spectrum m/z 246.1 (M+H)+.

1. temperatureThe mixture was cooled to rt
2. filtrationfiltered through a pad of Celite
3. washthe solids were rinsed with EtOAc
4. washThe filtrate was washed with water and brine
5. customdried
6. concentrationconcentrated
7. customThe residue was purified by column chromatography (
8. washeluting with a gradient from hexane to 90:10 hexane-EtOAc)

ORD-Eintrag

ord-7553d0a4f97a4f52bf4f12aeb3b87bf2

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08084620B2