Sodium Carbonate → (R)-tert-butyl 4-(4-ethoxy-1-(5'-fluoro-2'-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-tert-butyl 4-(1-(4-bromophenyl)-4-ethoxy-4-oxobutan-2-ylamino)-4-oxobutanoate, intermediate 9, (100 mg, 0.23 mmol) and 5-fluoro-2-methoxyphenylboronic acid (57.6 mg, 0.34 mmol) in toluene (1 mL) and EtOH (0.1 mL) is added Pd(PPh3)4 (26.1 mg, 0.023 mmol) and Na2CO3 (47.9 mg, 0.45 mmol). After stirring at 95° C. under nitrogen for 18 hours, the solution is cooled to ambient temperature and then quenched with aqueous 1 M HCl. 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 30:70) to give (R)-tert-butyl 4-(4-ethoxy-1-(5′-fluoro-2′-methoxybiphenyl-4-yl)-4-oxobutan-2-ylamino)-4-oxobutanoate (65 mg). HPLC retention time=1.44 minutes (condition B); MS (m+1)=488.3; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (t, J=7.1 Hz, 3H) 1.48 (s, 9H) 2.41-2.48 (m, 2H) 2.51-2.63 (m, 4H) 2.90 (dd, J=13.6, 6 Hz, 1H) 3.02 (dd, J=13.6, 6 Hz, 1H) 3.81 (s, 3H) 4.14-4.29 (m, 2H) 4.49-4.63 (m, 1H) 6.44 (d, J=8.6 Hz, 1H) 6.89-6.97 (m, 1H) 6.98-7.05 (m, 1H) 7.05-7.11 (m, 1H) 7.27 (d, J=8.1 Hz, 2H) 7.49 (d, J=8.1 Hz, 2H).

Provenance & Evidence