Acetic Acid → 2-Chloro-4-ethyl-5-fluoropyrimidine

Participants

Reaction Conditions

Reaction Steps

Diethyl 2-(2-chloro-5-fluoropyrimidin-4-yl)-2-methylmalonate (3.00 g, 9.85 mmol) was treated with glacial HOAc (25 mL) and 5N HCl (10 mL) and fitted with a reflux condenser and heated to 100° C. for 18 h. The reaction was cooled to RT and treated with H2O (30 mL) and DCM (45 mL) and the DCM layer separated and dried over MgSO4, filtered and concentrated. The crude residue was purified with flash chromatography (eluting with 100% DCM) affording 2-chloro-4-ethyl-5-fluoropyrimidine (328 mg, 21%) as a viscous pale yellow oil. MS (ESI, pos. ion) m/z: 161.0 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 8.34 (1H, s), 2.87 (2H, qd, J=7.6, 2.0 Hz), 1.29-1.37 (3H, t).

Provenance & Evidence