反应详情

A mixture of [2-iodo-5-(trifluoromethyl)phenyl]methanol (Intermediate 11, 3.09 g, 10.2 mmol), (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (Intermediate 6, 4.34 g, 20.5 mmol), (Ph3P)4Pd (1.42 g, 1.23 mmol) and Na2CO3 (9.11 g, 85.9 mmol) in benzene/EtOH/H2O (7:1:3, 250 mL) was heated at reflux for 24 h under N2. After cooling to room temperature, the aqueous phase was separated and extracted with CH2Cl2 (3×50 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography on silica gel (65×200 mm, 0-20% EtOAc in hexanes gradient) to afford 4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol. Rf=0.50 (20% EtOAc in hexanes). 1H NMR (500 MHz, CDCl3) δ 7.86 (s, 1H), 7.59 (d, J=6.7 Hz, 1H), 7.30 (d, J=7.9 Hz, 1H), 6.99 (d, J=8.6 Hz, 1H), 6.68 (d, J=12.0 Hz, 1H), 4.52 (br s, 1H), 4.46 (br s, 1H), 3.73 (s, 3H), 3.25-3.17 (m, 1H), 1.82 (br s, 1H), 1.24 (d, J=6.8 Hz, 6H).

1. temperaturewas heated
2. temperatureat reflux for 24 h under N2
3. customthe aqueous phase was separated
4. extractionextracted with CH2Cl2 (3×50 mL)
5. dry with materialThe combined organic layers were dried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customto give the crude product
8. customThis was purified by flash chromatography on silica gel (65×200 mm, 0-20% EtOAc in hexanes gradient)
9. customto afford 4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol