Diethyl Oxalate → Ethyl 3-benzyloxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate

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Reaction Conditions

Reaction Steps

Diethyl oxalate (7.66 g, 52.4 mmol) and ethyl benzyloxyacetate (10.2 g, 52.5 mmol) in dry tetrahydrofuran (70 ml) were treated at 22° C. with sodium hydride (2.31 g of a 60% dispersion in mineral oil, 57.7 mmol) and ethanol (40 μl). The tetrahydrofuran was then evaporated under reduced pressure and the residue treated with a mixture of 2-iminopiperidine hydrochloride (7.05 g, 52.2 mmol) in a solution of sodium ethoxide (26.0 mmol, prepared from 0.60 g of sodium) in ethanol (70 ml) and the resulting mixture heated at 60° C. for 4 h. Acetic acid (2 ml) was added and the ethanol was evaporated under reduced pressure. The residue was diluted with ethyl acetate washed successively with saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography on silica gel (elution toluene/ethyl acetate 1:1) gave 2.37 g (14% yield) of the title ester as white crystals; mp 97–99° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl3) δ (ppm): 1.33 (3H, t, J=7.1 Hz, CH3), 1.92 (2H, m, CH2), 2.0 (2H, m, CH2), 2.97 (2H, t, J=6.8 Hz, CH2), 4.02 (2H, t, J=6.3 Hz, NCH2), 4.36 (2H, q, J=7.1 Hz, OCH2), 5.27 (2H, s, OCH2), 7.3–7.51 (5H, m, aromatics). Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53. Found: C 65.72, H 6.33, N 8.41.

Provenance & Evidence