134000-96-7

75-16-1

2927-71-1

134000-96-7

Intermediate 55: Synthesis of 2-chloro-5-fluoro-4-methylpyrimidine. 2,4-Dichloro-5-fluoropyrimidine (1.02 g, 6.08 mmol) and Fe(acac)3 (215 mg, 0.61 mmol) were dissolved in a THF/NMP solvent mixture (38 mL/3 mL) and the mixture was cooled to 0 °C. A 3.0 M solution of Et2O of methylmagnesium bromide (3.04 mL, 9.12 mmol) was added slowly and dropwise. The reaction was completed after 30 min at 0 °C and quenched with saturated aqueous NH4Cl solution. Et2O was added for stratification and the aqueous layer was extracted several times with Et2O. The organic layers were combined, dried with Na2SO4, filtered and concentrated in vacuum. Purification by column chromatography (eluent: hexane to 10% EtOAc/hexane) afforded the target product 2-chloro-5-fluoro-4-methylpyrimidine as a waxy white solid (430 mg, 48% yield).1H NMR (400 MHz, CDCl3): δ 8.35 (s, 1H), 2.55 (d, J=2.5 Hz, 3H).