反应详情

温度

90 °C

The reaction was split into 4, using a quarter of the reagents shown in each: to a mixture of 4-bromo-3-(trifluoromethyl)benzonitrile (4 g, 16.00 mmol), phenylboronic acid (3.90 g, 32.0 mmol) and potassium carbonate (6.63 g, 48.0 mmol) in DMF (64 ml) was added palladium tetrakistriphenylphosphine(0) (1.849 g, 1.600 mmol). Each reaction was heated in the microwave at 150° C. for 30 minutes. The combined reaction mixtures were filtered through Celite®, washed with EtOAc and the solvent removed in vacuo. The residue was partitioned between EtOAc (100 ml) and water (100 ml) and the organic phase washed with sodium bicarbonate solution (100 ml). The organic phase was dried (MgSO4), filtered and the solvent removed in vacuo. The brown oil was triturated with DCM and filtered to give a pale yellow solid, 2-(trifluoromethyl)-4-biphenylcarboxamide (2.47 g) which was used without further purification. To 2-(trifluoromethyl)-4-biphenylcarboxamide (2 g, 7.54 mmol) in ethanol (80 ml) was added potassium hydroxide (4.23 g, 75 mmol) and water and the mixture heated to 90° C. for 18 hrs. The reaction mixture was concentrated in vacuo and the residue partitioned between DCM (100 ml) and 2M HCl (100 ml). The organic phase was isolated and dried (hydrophobic frit phase separator) and the solvent removed in vacuo to give the crude product. Chromatographic purification using the Biotage Horizon, reverse phase cartridge, eluting 5-100% MeCN in water to give the title compound as an off-white solid (960 mg). LCMS (ES−): C14H9F3O2 requires 266; found 265 [M−H+]

1. customwas used without further purification
2. concentrationThe reaction mixture was concentrated in vacuo
3. customthe residue partitioned between DCM (100 ml) and 2M HCl (100 ml)
4. customThe organic phase was isolated
5. customdried (hydrophobic frit phase separator)
6. customthe solvent removed in vacuo
7. customto give the crude product
8. customChromatographic purification
9. washeluting 5-100% MeCN in water