Acetic Acid → {Benzyloxycarbonyl-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylamino)-ethyl]-amino}-acetic acid ethyl ester

Participants

Reaction Steps

A solution of (benzyloxycarbonyl-{2-[(E)-1,3-dioxo-1,3-dihydro-isoindol-2-ylimino]ethyl}-amino)-acetic acid ethyl ester (7.7 mmol) in CH3CN (65 mL) is treated with sodium cyanoborohydride (1.92 g, 30.5 mmol), and acetic acid (6.8 mL, 118.8 mmol) is added with stirring under N2. After 5.5 h, the reaction solution is diluted with EtOAc (150 mL) and washed with saturated aqueous KHCO3 (3×50 mL) and saturated aqueous NaCl (50 mL). The organic phase is dried (MgSO4), filtered, and concentrated in vacuo. The residue is purified by silica gel chromatography (75:25 to 50:50 heptane:ethyl acetate gradient elution) to afford {benzyloxycarbonyl-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylamino)-ethyl]-amino}-acetic acid ethyl ester as an oil (2.66 g, 81%). MS: 426 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.79-7.91 (m, 2H), 7.69-7.79 (m, 2H), 7.17-7.39 (m, 5H), 5.04-5.21 (m, 2H), 4.87-5.04 (m, 1H), 4.04-4.23 (m, 4H), 3.48-3.59 (m, 2H), 3.18-3.38 (m, 2H), 1.10-1.30 (m, 3H).

Provenance & Evidence