Potassium Carbonate → 2-(Trifluoromethyl)-4-biphenylcarboxamide

Temperature

150 °C

The reaction was split into 4, using a quarter of the reagents 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 N,N-dimethylformamide (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 min. The combined reaction mixtures were filtered through celite, washed with ethyl acetate and the solvent removed in vacuo. The residue was partitioned between ethyl acetate (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 dichloromethane 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 h. The reaction mixture was concentrated in vacuo and the residue partitioned between dichloromethane (100 mL) and 2M HCl (100 mL). The organic phase was isolated and dried (phase separator) and the solvent removed in vacuo to give the crude product. Purification using the Biotage Horizon, reverse phase cartridge, eluting 5-100% MeCN in water to give an off-white solid the title compound (960 mg) (N2123-46-A5). MS (ES): C14H6F3O2 requires 266; found 265 (M−H+).

1. customThe reaction was split into 4
2. customThe combined reaction mixtures
3. filtrationwere filtered through celite
4. washwashed with ethyl acetate
5. customthe solvent removed in vacuo
6. customThe residue was partitioned between ethyl acetate (100 mL) and water (100 mL)
7. washthe organic phase washed with sodium bicarbonate solution (100 mL)
8. dry with materialThe organic phase was dried (MgSO4)
9. filtrationfiltered
10. customthe solvent removed in vacuo
11. customThe brown oil was triturated with dichloromethane
12. filtrationfiltered

ORD record

ord-f6ea2367ce934c23aeed73a0a942706a

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101775B2