Hydrochloric Acid → 3-(3-Fluoro-phenyl)-3-{2-oxo-1-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-pyrrolidin-3-yl}-propionic acid ethyl ester

Participants

Reaction Steps

To a mixture of 3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propylamine (1-8) (67 mg, 0.36 mmol) and 3-(3-fluoro-phenyl)-2-(2-oxoethyl)-pentanedioic acid 1-methyl ester 2-6A (110 mg, 0.36 mmol) in 5 mL 1,2-dichloroethane was added anhydrous hydrogen chloride in ethyl ether (1.0 M, 0.70 ml, 0.7 mmol). After 10 min, triethylamine (0.14 mL, 1.1 mmol) and 4 Å molecular sieves were added. The mixture was stirred for 3 hr. It was treated with NaBH(OAc)3 (111 mg, 0.53 mmol) and stirred for 12 hr. The reaction was quenched with 10% NaHCO3 and extracted with EtOAc (×3). The combined organic layers were washed with brine and dried (Na2SO4). After solvent removal the residue was purified by flash silica chromatography (CHCl3 /MeOH, 10:1) to provide the enantiomeric pair 2-7A as an oil.

Provenance & Evidence