Naphthoxyacetic acid → (3RS,4RS)-3-[N-((1-Naphthyloxy)Acetyl)Valinyl]Amino-5-Fluoro-4-Hydroxypentanoic Acid, tert-Butyl Ester

Participants

Reaction Steps

To a solution of (1-naphthyloxy)acetic acid (0.202 g, 1.0 mmol) in in dimethylformamide(4.0 mL)-CH2Cl2 (6.0 mL) at 0° C. (ice bath) under nitrogen was added hydroxybenzotriazole hydrate (0.168 g) followed by 1-ethyl-3-(3′,3′-dimethyl-1′-aminopropyl)carbodiimide hydrochloride (0.249 g, 1.3 mmol). After stirring for 10 min, the mixture was treated with a solution of (3RS,4RS)-3-(valinyl)amino-5-fluoro-4-hydroxypentanoic acid, tert-butyl ester (0.319 g, 1.04 mmol) in CH2Cl2(8.0 mL). After stirring at 0° C. for 1 hr and at room temperature for 3 hrs, the mixture was partitioned between EtOAc-water. The organic phase was washed with water, 5% KHSO4, saturated NaHCO3 and saturated NaCl solutions, dried over anhydrous Na2SO4 and evaporated to dryness. The residue was purified by flash chromatography on silica gel eluting with EtOAc-hexane (3:2) to give the title compound (0.307 g, 63%) as a white solid. TLC(MeOH-CH2Cl2; 1:9) Rf=0.69.

Provenance & Evidence