反应详情

To a solution of 2-iodo-5-(trifluoromethyl)benzonitrile (2.0 g, 6.7 mmol) and (5-isopropyl-2-methoxyphenyl)boronic acid (1.6 g, 8.4 mmol) in dimethyl ethylene glycol (30.4 mL) was added 2M Na2CO3 (6.8 mL), ethanol (9.6 mL), and water (10 mL). The solution was degassed with nitrogen for 2 minutes. Pd(PPh3)4 (774 mg, 0.67 mmol) was added and the solution was degassed with nitrogen again for 2 minutes. The solution was divided equally into two 40 mL microwave tubes. Each tube was degassed with nitrogen for 1 minute, sealed, and placed in a microwave reactor. The wattage was set for 200 W until the temperature reached 150° C. and then the temperature was held at 150° C. for ten minutes. The tubes were then cooled to room temperature, combined, poured into H2O (50 mL), and extracted with EtOAc (100 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 15% CH2Cl2/hexanes afforded 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carbonitrile as a light yellow oil. Rf=0.65 (25% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.97 (s, 1H), 7.85 (d, J=8.0 Hz, 1H), 7.63 (d, J=8.0 Hz, 1H), 7.31 (dd, J=8.5, 2.0 Hz, 1H), 7.12 (d, J=2.0 Hz, 1H), 6.97 (d, J=8.5 Hz, 1H), 3.82 (s, 3H), 2.93 (m, 1H), 1.27 (d, J=7.0 Hz, 6H).

1. customThe solution was degassed with nitrogen for 2 minutes
2. customthe solution was degassed with nitrogen again for 2 minutes
3. customEach tube was degassed with nitrogen for 1 minute
4. customsealed
5. customplaced in a microwave reactor
6. customreached 150° C.
7. waitthe temperature was held at 150° C. for ten minutes
8. additionpoured into H2O (50 mL)
9. extractionextracted with EtOAc (100 mL)
10. washThe organic layer was washed with brine (50 mL)
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customPurification by flash chromatography with 15% CH2Cl2/hexanes