Sodium Carbonate → (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(2',5'-dichlorobiphenyl-4-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (1.005 g, 2.60 mmol), 2,5-dichlorophenylboronic acid (0.745 g, 3.90 mmol), Pd(PPh3)4 (0.301 g, 0.260 mmol) and 2 M aqueous Na2CO3 (2.60 ml, 5.20 mmol) in 1,2-dimethoxyethane (20 ml) is allowed to stir at 95° C. under nitrogen for 3 hours. The reaction mixture is cooled to room temperature and diluted with brine. The two phases are separated. The products are extracted twice with ethyl acetate (2×100 ml) 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-(2′,5′-dichlorobiphenyl-4-yl)butanoate (1.09 g); HPLC retention time=1.50 minutes (condition B); MS (ES+)=352.00 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.1 Hz, 3H) 1.41 (s, 9H) 2.45-2.58 (m, 2H) 2.85-3.00 (m, 2H) 4.17 (t, J=7.1 Hz, 2H) 4.20 (br s, 1H) 5.06-5.08 (m, 1H) 7.23-7.28 (m, 3H) 7.31-7.40 (m, 4H).

Provenance & Evidence