Triethylamine → (benzyloxycarbonyl)difluoromethyl 5-(Cbz-amino)-4-oxopentanoate

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Reaction Steps

Triethylamine (3.5 mL; 2.5 g; 25 mmol) was added using a syringe to a stirred mixture of the crude product of 3a (8.6 g; 20 mmol) and 5-(Cbz-amino)-4-oxopentanoic acid (6.63 g; 25 mmol) in dry acetonitrile (100 mL). The mixture was refluxed for 18 h, then the solvent was evaporated and the dark red residue was dissolved in diethyl ether (100 mL) and 0.5 M HCl (100 mL). After mixing thoroughly, the ether layer was washed with water (2×15 mL), saturated NaHCO3 (2×15 mL), and saturated NaCl solution (1×15 mL), then dried (MgSO4). After filtration and evaporation, the residue was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with dichloromethane-diethyl ether (9:1) (1000 mL), collecting 10×75 mL fractions. After evaporation of fractions 2-5 and vacuum-drying (0.02 mm Hg), 6.7 g (74%) product was obtained (red-orange solid mp 48-50° C.).

Provenance & Evidence