Sodium hydride → Tert-butyl 6-((methoxycarbonyl)methoxy)-5-(benzyloxy)-2-methoxypyrimidine-4-carboxylate

Participants

Reaction Steps

tert-Butyl 5-(benzyloxy)-2-methoxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate (300 mg, 0.903 mmol) and sodium hydride (36.1 mg, 0.903 mmol) were stirred in anhydrous DMF (903 μl) at 0° C. under argon for 30 min. Methyl 2-bromoacetate (83 μl 0.90 mmol) was added and the mixture was stirred at rt for 3 h. The reaction was carefully quenched with water at 0° C. The reaction mixture was extracted with EtOAc (3×). The combined organic layers were washed with water, brine, dried over Na2SO4, concentrated and purified by flash chromatography (hexanes/EtOAc, eluted at ca. 30% EtOAc) to give tert-butyl 5-(benzyloxy)-2-methoxy-6-(2-methoxy-2-oxoethoxy)pyrimidine-4-carboxylate (109 mg, 0.270 mmol, 29.9% yield) as a colorless oil and Example 267A (117 mg, 0.289 mmol, 32.1% yield) as a colorless oil. 1H NMR (500 MHz, chloroform-d) δ 7.49-7.44 (m, 2H), 7.37-7.32 (m, 2H), 7.32-7.27 (m, 1H), 5.12 (s, 2H), 4.74 (s, 2H), 4.00 (s, 3H), 3.75 (s, 3H), 1.51 (s, 9H). LC-MS (ESI) 349.0 (M+H-t-Bu), retention time=2.07 min (Method B).

Provenance & Evidence