Acetic Acid → 2-(2,2-Dimethoxyethoxy)-4-ethoxypyrimidine

Participants

Reaction Steps

To a suspension of 60% NaH/mineral oil (2.55 g, 63.96 mmol) in anhydrous DMF (70 mL) at 0° C. under nitrogen atmosphere was slowly added glycolaldehyde dimethyl acetal (Aldrich, 5.65 g, 53.3 mmol). The mixture was stirred at ambient temperature for 1 hour and then transferred to a solution of the product from step (a) (8.05 g, 50.76 mmol) in anhydrous DMF (70 mL) at -55° C. over 15 minutes. The mixture was allowed to warm to -20° C. over 2 hours and then neutralized with AcOH. Solvent was evaporated in vacuo and the residue partitioned between H2O and CH2Cl2. The aqueous phase was extracted with CH2Cl2 and the combined organic phase was dried (Na2SO4) and evaporated in vacuo. The residue was flash chromatographed (EtOAc/hexanes, 1:4) to give the desired product (7.92 g, 69%) as a colourless oil: 1H NMR (CDCl3): δ 1.37 (t, J=7.0 Hz, 3H), 3.44 (s, 6H), 4.36-4.43 (m, 4H), 4.78 (t, J=5.0 Hz, 1H), 6.34 (d, J=6.0 Hz, 1H), 8.15 (d, J=6.0 Hz, 1H); MS m/z229 (M=1, 13%), 197 (100%). Anal Calcd. for C10H16N2O4 : C, 52.62; H, 7.07; N, 12.27. Found: C, 52.45; H, 7.01; N, 12.26.

Provenance & Evidence