Cesium carbonate → 4-Cyclobutyl-2-fluoro-1-nitrobenzene

Temperatur

90 °C

A solution of trifluoro-methanesulfonic acid 3-fluoro-4-nitro-phenyl ester (1.8 g, 6.2 mmol), cyclobutyl boronic acid (0.78 g, 7.5 mmol), Pd(dppf)Cl2 (0.40 g, 0.5 mmol), and 2M aqueous cesium carbonate (aq) (5 mL, 9.9 mmol) in toluene (10 ml) was degassed with argon for 10 minutes and then heated to 90° C. for 2.5 hours. The reaction mixture was then cooled to room temperature and filtered through hyflo®. The reaction mixture was partitioned between ethyl acetate (70 mL) and water (70 mL). The organic layer was isolated, then washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The resultant solid was subjected to flash chromatography (Si-PPC, gradient 0% to 30%, DCM in pentane) to afford the title compound as a yellow liquid (0.504 g, 42%). 1H NMR (DMSO-d6): 8.08 (1H, t, J=8.3 Hz), 7.44 (1H, d, J=13.2 Hz), 7.28 (1H, d, J=8.5 Hz), 3.65 (1H, m), 2.33 (2H, m), 2.13 (2H, m), 1.99 (1H, m), 1.84 (1H, m).

1. temperatureThe reaction mixture was then cooled to room temperature
2. filtrationfiltered through hyflo®
3. customThe reaction mixture was partitioned between ethyl acetate (70 mL) and water (70 mL)
4. customThe organic layer was isolated
5. washwashed with brine (50 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD-Eintrag

ord-1e7836299736452ca1ad55ec1e9a1399

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08293763B2