4-Nitrobenzoic Acid → Benzyl(cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-[(4-nitrobenzoyl)oxy]pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of benzyl (trans)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-hydroxypyrrolidine-1-carboxylate (2.93 g) in tetrahydrofuran (100 ml) was added p-nitrobenzoic acid (1.89 g), triphenyl phosphine (2.23 g) and di-tert-butyl azodicarboxylate (1.95 g). The reaction mixture was heated at 40° C. for 18 h and was poured into saturated sodium bicarbonate (200 ml). The aqueous layer was extracted with ethyl acetate (2×200 ml), dried MgSO4, filtered and concentrated. MPLC chromatography on a biotage 40 M column with 15-20% ethyl acetate/heptane provided the title compound as an oil (3.19 g, 84%): 1H NMR (400 MHz, CDCl3) δ) 8.35, 8.20, 7.49-7.22, 6.23, 5.81, 5.32, 5.20, 5.05, 4.83, 4.27, 3.95-3.85, 3.51, 2.58-2.41, 1.63, 1.32-1.14; (MS/CI) calcd for C33H31Cl2N5O3+H 664.5, found 664.1.

Provenance & Evidence