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

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate, (3.12 g, 8.08 mmol), and 5-fluoro-2-methoxyphenylboronic acid (2.2 g, 12.93 mmol) in toluene (52 mL) and is added PdCl2(dppf)CH2Cl2 adduct (0.66 g, 0.81 mmol) and 2M aq. Na2CO3 (8.1 mL, 16.16 mmol). After stirring at 95° C. under nitrogen for 4 hours, the solution is cooled to ambient temperature and then quenched with ice water. The crude is diluted with ethyl acetate. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on silica gel (eluent: heptane/EtOAc=100:0 to 50:50) to give (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(5′-fluoro-2′-methoxybiphenyl-4-yl)butanoate (2.86 g). HPLC retention time=1.80 minutes (condition A); MS (m+1)=432.2; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.1 Hz, 3 H) 1.45 (s, 9 H) 2.45-2.65 (m, 2 H) 2.83-2.94 (m, 1 H) 2.94-3.09 (m, 1 H) 3.80 (s, 3 H) 4.20 (q, J=7.2 Hz, 2 H) 4.24-4.33 (m, 1 H) 5.11 (br. s., 1 H) 6.90-6.96 (m, 1 H) 7.00 (dd, J=7.8, 3.3 Hz, 1 H) 7.06 (dd, J=9.2, 3.2 Hz, 1 H) 7.27 (d, J=7.8 Hz, 2 H) 7.49 (d, J=7.8 Hz, 2 H)

Provenance & Evidence