Acetic Acid → Methyl 4-(4-fluorophenyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate

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Reaction Steps

A round bottom flask was charged with 4-fluorobenzaldehyde (2.00 mL, 18.6 mmol, 1 equiv), methyl 3,3-dimethoxypropionate (2.49 mL, 18.6 mmol, 1 equiv), urea (1.68 g, 28.0 mmol, 1.5 equiv), and copper (I) chloride (184 mg, 1.86 mmol, 0.1 equiv). THF (18.6 mL) was added, followed by acetic acid (0.110 mL, 1.86 mmol, 0.1 equiv) and BF3.OEt2 (3.07 mL, 24.2 mmol, 1.3 equiv). The slurry was heated to reflux for 24 hours, then stirred at room temperature for an additional 36 hours. The mixture was diluted with water and carefully neutralized with satd. NaHCO3. Ethyl acetate was added, and the biphasic solution was filtered through celite. The layers were separated, and the aqueous layer was washed with an additional portion of ethyl acetate. The combined organic extracts were washed with satd. NaCl, dried over Na2SO4, filtered and concentrated to a foamy solid. The residue was purified by flash chromatography (50% Ch2Cl2/ethyl acetate) to provide 535 mg of the product as an off-white powder (535 mg, 11%). NMR 1H NMR (400 MHz, DMSO-D6) δ ppm 9.25 (d, J=5 Hz, 1H), 7.72 (br s, 1H), 7.30-7.26 (m, 3H), 7.17 (t, J=8.9 Hz, 2H), 5.14 (d, J=3 Hz, 1H), 3.56 (s, 3H) MS m/z 251 [M+H]+

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