4-Methylpyrimidine → 1-(4-Fluoro-phenyl)-2-pyrimidin-4-YL-ethanone

Participants

Reaction Steps

To a stirred solution of 4-methylpyrimidine (20.64 g, 0.22 mol) and ethyl 4-fluorobenzoate (36.9 g, 0.22 mol) in dry THF (100 mL) at 0° C. under nitrogen was added lithium bis(trimethylsilyl)amide (1M in THF, 440 mL, 0.44 mol) over a 2 h period. A white precipitate deposited during the addition and this suspension was stirred at room temperature overnight. The reaction was diluted with 100 mL of water and filtered. The filtrate was washed with water (3×) and dried. The solution was diluted with ethyl acetate (100 mL) and the organic phase separated. The aqueous phase was further extracted with ethyl acetate (100 mL). Organic phases were dried (MgSO4) and concentrated and combined with the filtrate to give a combined yield of 47 g (98%) of product. 1H NMR (CDCl3) exists as a 2:1 mixture of enol:keto tautomers: 6 enol form: 5.95 (s, 1H), 6.92 (dd, J=1.2, 5.7 Hz, 1H), 7.06–7.14 (m, 2H), 7.83 (dd, J=5.4, 8.7 Hz, 2H), 8.40 (d, J=5.7 Hz, 1H), 8.8 (s, 1H); keto form: 4.42 (s, 2H), 7.12–7.18 (m, 2H), 7.34 (d, J=4.2 Hz, 1H), 8.06 (dd, J=5.3, 8.8 Hz, 2H), 8.67 (d, J=5.1 Hz, 1H), 9.16 (s, 1H); APESI-MS m/z 215 (M−1)−.

Provenance & Evidence