反应详情

温度

95 °C

A mixture of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (4.89 g, 12.66 mmol), 3-chlorophenylboronic acid (2.97 g, 18.99 mmol), Pd(PPh3)4 (1.463 g, 1.266 mmol) and 2 M aqueous Na2CO3 (12.66 ml, 25.3 mmol) in 1,2-dimethoxyethane (100 ml) is allowed to stir at 95° C. under nitrogen for 3 hours. The reaction mixture is cooled to room temperature and quenched with brine. The two phases are separated. The mixture is extracted twice with ethyl acetate from the aqueous layer. The combined organic layer is washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30) to give (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (3.33 g); HPLC retention time=1.44 minutes (condition B); MS (ES+)=318.26 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.2 Hz, 3 H) 1.41 (s, 9 H) 2.47 (A of ABX, Jab=15.8 Hz, Jax=5.9 Hz, 1 H) 2.52 (B of ABX, Jab=15.8 Hz, Jbx=5.4 Hz, 1 H) 2.83-2.89 (m, 1 H) 2.95-3.00 (m, 1 H) 4.17 (q, J=7.2 Hz, 2 H) 4.18 (br s, 1 H) 5.07 (br s, 1 H) 7.26-7.37 (m, 4 H) 7.43-7.51 (m, 3 H) 7.55 (br t, J=1.8 Hz, 1 H).

1. temperatureThe reaction mixture is cooled to room temperature
2. customquenched with brine
3. customThe two phases are separated
4. extractionThe mixture is extracted twice with ethyl acetate from the aqueous layer
5. washThe combined organic layer is washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30)