2,4-Dichloro-5-fluoropyrimidine → 2-Chloro-5-fluoro-4-methylpyrimidine

Participants

Reaction Conditions

Reaction Steps

A solution of 2,4-dichloro-5-fluoropyrimidine (2.5 g, 14.97 mmol) and iron(III) acetylacetonate (1.058 g, 2.99 mmol) in THF (100 mL) and NMP (10 mL) was chilled below 0° C. and methyl magnesium chloride (5.99 mL, 18.0 mmol, 3.0 M solution in THF) was added dropwise over 10 minutes. After stirring for 2 hours at 0° C., the mixture was quenched with 200 mL saturated NH4Cl and extracted twice with 200 mL EtOAc. The combined organic extracts were washed with 200 mL saturated NH4Cl and 200 mL brine, dried over Na2SO4 and concentrated. Purification by chromatography (Grace Reveleris 80 g column, eluted with 0-20% EtOAc/heptane, 35 mL/min) provided the title compound (1.13 g, 7.70 mmol, 51% yield). GC/MS (EI+) m/z 146.0 (M+); 1H NMR (400 MHz, CDCl3) δ 8.36 (s, 1H), 2.55 (d, J=2.5, 3H); 13C NMR (101 MHz, CDCl3) δ 158.78, 158.61, 157.34, 154.92, 154.89, 154.74, 145.86, 145.63, 17.74, 17.73.

Provenance & Evidence