Ammonium Chloride → 1-(4-Fluorophenyl)-2-(3-fluoropyridin-4-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

Lithium hexamethyldisilazide (1.0M in THF, 17.9 mL, 17.9 mmol) was cooled to 0° C. and 3-fluoro-4-methylpyridine (1.00 g, 0.926 mmol) in THF (50 mL) was added dropwise, keeping the solution temperature below 5° C. The mixture was then stirred for 1 hour at 0° C. and ethyl 4-fluorobenzoate in THF (50 mL) was added dropwise. The reaction was allowed to warm slowly to rt with stirring overnight. Aqueous ammonium chloride was added and the mixture was poured into EtOAc. The organic phase was separated dried (Na2SO4) and concentrated. Silica gel chromatography using a 10-50% EtOAc/heptanes gradient yielded 1.83 g (89%) of Ex 1-Step 6 product as a white solid: LCMS m/z 234.4 (M+1); 1H NMR (400 MHz, MeOH-d4) δ 8.41 (d, J=1.7 1H), 8.32 (d, J=4.8, 1H), 8.14 (dd, J=8.9, 5.4, 2H), 7.38 (dd, J=5.9, 5.1, 1H), 7.25 (dd, J=9.0, 9.0, 2H), 4.52 (s, 2H).

Provenance & Evidence