Butanedioic acid, 1-butyl ester → (R)-benzyl 3-(4-butoxy-4-oxobutanamido)-4-(3'-chlorobiphenyl-4-yl)butanoate

Participants

Reaction Steps

A mixture of (R)-benzyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride (Intermediate 8-4: 150 mg, 0.360 mmol), 4-butoxy-4-oxobutanoic acid (107 mg, 0.540 mmol, 88% purity), EDCl (104 mg, 0.540 mmol), DIPEA (0.094 ml, 0.540 mmol) and HOAt (73.6 mg, 0.540 mmol) in DMF (2 ml) is allowed to stir at room temperature for 1 hour. The reaction mixture is diluted with water, and then the precipitated solid is collected on a funnel, washed with H2O, and dried under reduced pressure to give crude. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 0:100) to give (R)-benzyl 3-(4-butoxy-4-oxobutanamido)-4-(3′-chlorobiphenyl-4-yl)butanoate (178.9 mg); HPLC retention time=1.47 minutes (condition B); MS (m+1)=536.42; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.90-0.94 (m, 3 H) 1.31-1.40 (m, 2 H) 1.56-1.63 (m, 2 H) 2.39-2.42 (m, 2 H) 2.48-2.62 (m, 4 H) 2.84 (A of ABX, Jab=13.6 Hz, Jax=8.1 Hz, 1 H) 2.97 (B of ABX, Jab=13.6 Hz, Jbx=6.6 Hz, 1 H) 4.07 (t, J=6.7 Hz, 2 H) 4.48-4.56 (m, 1 H) 5.12 (A of AB, J=12.1 Hz, 1 H) 5.18 (B of AB, J=12.1 Hz, 1 H) 6.27 (br d, J=7.7 Hz, 1 H) 7.20 (d, J=8.3 Hz, 1 H) 7.29-7.39 (m, 7 H) 7.42-7.47 (m, 3 H) 7.54-7.55 (m, 1 H).

Provenance & Evidence