Sodium Carbonate → (R)-3-(3-carboxy-propionylamino)-4-(4'-fluoro-biphenyl-4-yl)-butyric acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence