Diisopropylethylamine → (R)-tert-butyl 3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoate

Participants

Reaction Steps

A solution of (R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid (142 mg, 0.417 mmol), 3-amino-propionic acid methyl ester hydrochloride (76 mg, 0.542 mmol), WSC hydrochloride (120 mg, 0.626 mmol), 1-hydroxy-7-azabenzotriazole (85 mg, 0.626 mmol) and DIPEA (0.219 ml, 1.251 mmol) in DMF (4 mL) is allowed to stir at room temperature under nitrogen for 13 hours. The reaction is quenched with H2O. The products are extracted with ethyl acetate, washed with aqueous 1M HCl and then with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on 12 g of silica gel (heptane/EtOAc=70:30 to 0:100) to give (R)-tert-butyl 3-(biphenyl-4-ylmethyl)-4-(3-methoxy-3-oxopropylamino)-4-oxobutanoate (164 mg, 91%). HPLC retention time=1.59 minutes (condition A); MS (ES+)=425.4 (m); 369.4 (m-tBu+1; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.24-2.44 (m, 2 H) 2.67-2.79 (m, 3 H) 2.89-2.96 (m, 1 H) 3.28-3.36 (m, 1 H) 3.45-3.53 (m, 1 H) 7.23 (d, J=5.8 Hz, 2 H) 7.33 (t, J=7.35 Hz, 1 H) 7.41-7.44 (m, 2 H) 7.51 (d, J=8.1 Hz, 2 H) 7.58 (d, J=7.4 Hz, 2 H).

Provenance & Evidence