(3-Chlorophenyl)boronic acid → (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3'-chlorobiphenyl-4-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

A suspension of give (R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (2.00 g, 4.46 mmol), 3-chlorophenylboronic acid (1.046 g, 6.69 mmol), Pd(PPh3)4 (0.515 g, 0.446 mmol) and Na2CO3aq (4.46 ml, 8.92 mmol) in Toluene (30 ml) is allowed to stir under nitrogen at 95° C. for 19 hr. The reaction mixture is cooled to ambient temperature, and diluted with brine and EtOAc. The products are extracted twice with EtOAc, washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35) to give (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (1.03 g); HPLC retention time=1.74 minutes (condition B); MS (ES+)=380.2 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 9 H) 2.52 (A of ABX, Jab=15.9 Hz, Jax=5.8 Hz, 1 H) 2.58 (B of ABX, Jab=15.9 Hz, Jbx=5.6 Hz, 1 H) 2.81-2.98 (m, 2 H) 4.19 (br s, 1 H) 5.07 (br d, 1 H) 5.12 (A of AB, J=12.3 Hz, 1 H) 5.17 (A of AB, J=12.3 Hz, 1 H) 7.20-7.22 (m, 2 H) 7.28-7.39 (m, 7 H) 7.42-7.47 (m, 3 H) 7.53-7.54 (m, 1 H).

Provenance & Evidence