Pyridine → 3-(3-Benzyloxy-phenyl)-3-(cyclobutanecarbonyl-amino)-2-oxo-propionic acid ethyl ester

Participants

Reaction Steps

A slurry of (3-benzyloxy-phenyl)-(cyclobutanecarbonyl-amino)-acetic acid (4.77 g, 14.1 mmol), pyridine (3.4 mL, 42.2 mmol) and DMAP (cat.) in anhydrous THF (26 mL) was charged dropwise with chloro-oxo-acetic acid ethyl ester (3.13 mL, 28.1 mmol) and heated to reflux for 1.5 h. The white precipitate was filtered through a fritted glass Buchner funnel into a flask containing H2O and EtOAc and the aqueous phase was separated from the organic phase. The aqueous was washed with EtOAc (3×) and the combined EtOAc layers were washed with brine (1×), dried over Na2SO4, filtered and concentrated in vacuo resulting in a yellow/orange oil. The oil was dissolved in anhydrous EtOH (28 mL) and a solution of 21 wt % of sodium ethoxide (NaOEt) in EtOH (2.0 mnL) was added at 0° C. and warmed to rt. The reaction mixture was concentrated in vacuo and the crude material was chromatographed on silica gel [eluting with 2% EtOAc in CHCl3], yielding the title compound as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 1.26 (t, J=7.2 Hz, 3H), 1.80-2.04 (m, 2H), 2.09 (m, 4H), 3.06 (quint, J=8.4 Hz, 1H) 4.17-4.30 (m, 2H), 5.04 (s, 2H), 6.18-6.32 (m, 2H), 6.86-7.00 (m, 3H), 7.22-7.48 (m, 5H); MS (ES+): m/z 396.03 (100) [MH+]; HPLC: tR=3.09 min (MicromassZQ, nonpolar—5 min).

Provenance & Evidence