反应详情

温度

95 °C

A mixture of (R)-4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (50 mg, 0.129 mmol), 4-fluorophenylboronic acid (27.2 mg, 0.194 mmol), Pd(Ph3P)4 (14.96 mg, 0.013 mmol) and aqueous Na2CO3 (0.129 mL, 0.259 mmol) in toluene (1 mL) is allowed to stir at 95° C. under nitrogen. After stirring for 13 hours, the solution is cooled to ambient temperature and then quenched with aqueous 1 M HCl. The products are extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and then lyophilized to give (R)-3-(3-carboxy-propionylamino)-4-(4′-fluoro-biphenyl-4-yl)-butyric acid ethyl ester (29.2 mg). HPLC retention time=1.26 minutes (condition B); MS (m+1)=402.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (t, J=7 Hz, 3 H) 2.47-2.67 (m, 6 H) 2.87 (A of ABX, Jab=13.7 Hz, Jax=7.9 Hz, 1 H) 2.99 (B of ABX, Jab=13.7 Hz, Jbx=6.6 Hz, 1 H) 4.12-4.23 (m, 2 H) 4.47-4.55 (m, 1 H) 6.52 (br d, J=8.6 Hz, 1 H) 7.08-7.14 (m, 2 H) 7.24 (d, J=8.4 Hz, 2 H) 7.46-7.55 (m, 4 H).

1. stirringAfter stirring for 13 hours
2. temperaturethe solution is cooled to ambient temperature
3. customquenched with aqueous 1 M HCl
4. extractionThe products are extracted with ethyl acetate
5. washwashed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)