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

Participants

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 THF (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 hours. The THF was removed under reduced pressure and the residue was dissolved in a solution of sodium ethoxide (0.072 mol, prepared from 1.65 g of sodium) in ethanol (200 ml). Then 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 hours. Acetic acid (5 ml) was added and the ethanol was removed 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 followed by brine, dried over anhydrous magnesium sulfate, filtered, 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 compound; mp 109-110° C. 1H NMR 400 MHz (CDCl3) δ: 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