Diethyl Oxalate → Ethyl 5-(benzyloxy)-2-(methylthio)-6-oxo-1,6-dihydropyrimidine-4-carboxylate

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Reaction Conditions

Reaction Steps

A solution of diethyl oxalate (21.06 g, 0.144 mol) and ethyl benzyloxyacetate (28.0 g, 0.144 mol) in dry tetrahydrofliran (200 ml) was treated at 22° C. with sodium hydride (6.34 g of a 60% dispersion in mineral oil, 0.158 mol). Ethanol (0.05 ml) was added and the resulting mixture was stirred at 22° C. for 18 h. The tetrahydrofuran was then evaporated under reduced pressure and the residual orange syrup was dissolved in a solution of sodium ethoxide (0.072 mol prepared from 1.65 g of sodium) in ethanol (200 ml). Powdered 2-methyl-2-thiopseudourea sulfate (20.1 g, 0.072 mol) was added and the resulting mixture was heated at 60° C. for 6 h. Acetic acid (5 ml) was then added to the gel-like reaction mixture and the ethanol was evaporated under reduced pressure. The residual paste was partitioned between water and dichloromethane and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with saturated sodium bicarbonate, brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography on silica gel (elution with a gradient of ethyl acetate 0–20% in toluene) followed by crystallization from ethyl acetate-hexane gave 8.34 g (18% yield) of the title ester as white needles; mp 109–110° C. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.35 (3H, t, J=7.1 Hz, CH3), 2.62 (3H, s, SCH3), 4.37 (2H), q, J=7.1 Hz, CH2), 5.28 (2H, s, OCH2), 7.35–7.52 (5H, m, aromatics), 12.2 (1H, broad s, NH). Anal. Calcd for C15H16N2O4S: C, 56.23; H, 5.03; N, 8.74. Found: C, 56.23; H, 4.86; N, 8.76.

Provenance & Evidence