960299-06-3

4316-97-6

124-41-4

960299-06-3

4,6-Dichloro-5-methylpyrimidine (1.00 g, 6.13 mmol) was dissolved in methanol (50 mL) at 0 °C, followed by the addition of solid sodium methanolate (0.348 g, 6.44 mmol) in batches. The reaction mixture was gradually warmed to room temperature and stirred continuously at that temperature for 4 hours, after which it was warmed to 50 °C and continued stirring for 12 hours. Sodium methanol (0.348 g, 6.44 mmol) was again added and the reaction mixture was stirred at 50 °C for 4 hours. Finally, a third batch of sodium methanolate (0.348 g, 6.44 mmol; total 3 equiv.) was added and the reaction mixture was stirred at 50 °C for 20 min and the completion of the reaction was confirmed by HPLC monitoring. The reaction mixture was concentrated and partitioned with ethyl acetate and saturated aqueous ammonium chloride solution. The organic and aqueous phases were separated and the aqueous phase was extracted once more with ethyl acetate. The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated to afford the colorless oily target product 4-chloro-6-methoxy-5-methylpyrimidine (0.829 g, 85% yield), which could be used for subsequent reactions without further purification. The product was characterized by 1H-NMR (400 MHz, CDCl3): δ 8.42 (s, 1H), 4.02 (s, 3H). The mass spectrum (ESI positive ion mode) showed m/e 159 (M + 1).