反应详情

温度

100 °C

To a solution of 2-[4-amino-3-bromo-5-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid methyl ester (13.8 g, 29.6 mmol) in DME (anhydrous, 100 mL) under argon atmosphere were added 4-trifluoromethylphenylboronic acid (6.8 g, 35.8 mmol), CsF (11 g, 72.3 mmol), and Pd(PPh3)4 (3.4 g, 2.94 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). On the next day, a mixture water and EtOAc (100 mL/100 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by a short silica gel column chromatography by use of Heptane-EtOAc (4:1) to give the product (14.7 g, 94%) as a yellowish oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.70 (d, J=8.2 Hz, 2H), 7.59 (d, J=8.0 Hz, 2H), 6.78 (dd, J=9.6, 1.4 Hz, 2H), 4.43 (q, J=8.0 Hz, 2H), 3.95 (br s, 2H), 3.66 (s, 3H), 3.39 (t, J=7.7 Hz, 1H), 2.25-2.07 (m, 2H), 2.03-1.91 (m, 2H), 1.88-1.75 (m, 3H), 1.69-1.52 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 174.6, 144.8, 133.1, 129.2, 128.6, 126.3, 125.7 (q, 3JCF=3.6 Hz), 123.8, 123.3 (q, 1JCF=277.6 Hz), 111.4, 66.5 (q, 1JCF=35.4 Hz), 52.0, 49.0, 40.9, 34.1, 28.3, 28.1, 18.5.

1. customthe layers were separated
2. dry with materialThe organic phase was dried over MgSO4
3. customevaporated
4. customto give a crude yellow oil, which
5. customwas purified by a short silica gel column chromatography by use of Heptane-EtOAc (4:1)