2-Chloro-5-methoxy-4-methylpyrimidine

75-16-1

19646-07-2

1245506-61-9

To a mixed solution of 2,4-dichloro-5-methoxypyrimidine (1 g, 5.59 mmol) in tetrahydrofuran (32.2 mL) with N-methyl-2-pyrrolidinone (2.424 mL) was added ferric acetylacetonate (0.197 g, 0.559 mmol) and the mixture was cooled to 0°C under nitrogen protection. Subsequently, methylmagnesium bromide solution (2.62 mL, 8.38 mmol, 3.2 M, dissolved in 2-methyltetrahydrofuran) was added slowly and dropwise. The reaction mixture was stirred at 0 °C for 30 min under nitrogen atmosphere. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution (10 mL) and the mixture was gradually warmed to room temperature. Ether was added for partitioning and the aqueous phase was further extracted with ether (4 x 15 mL). All organic phases were combined, dried over hydrophobic glass material and concentrated under reduced pressure to give an orange oily crude product. The crude product was dissolved in dichloromethane (3 mL) and purified by chromatography on a silica gel column (25 g) using a gradient elution of 0-30% cyclohexane/ethyl acetate, and 10 column volumes of eluate were collected. Fractions containing the target product were combined and the solvent was evaporated under reduced pressure to afford the white solid product 2-chloro-5-methoxy-4-methylpyrimidine (475 mg, 3.00 mmol, 54% yield).LCMS (2 mm formic acid): retention time Rt = 0.64 min, [M+H]+ = 159.