General procedure for the preparation of 2,4-dichloropyrimidine-5-carbaldehyde: In a 2L round-bottomed flask, a solution of isopropylmagnesium chloride lithium chloride complex in THF (2M, 184mL, 368mmol) was added dropwise to a solution of 5-bromo-2,4-dichloropyrimidine (49.6g, 218mmol) in THF (1000mL) over a period of ~30 minutes at ~-78 °C (1000 mL). The reaction mixture was stirred at about -78 °C for about 30 minutes. Subsequently, morpholine-4-carbaldehyde (75.0 g, 653 mmol) was added dropwise over about 30 minutes at the same temperature. After continuing to stir at about -78°C for about 30 minutes, the reaction mixture was slowly warmed to about -35°C and stirred at this temperature for about 30 minutes. Upon completion of the reaction, 1N HCl aqueous solution (250 mL) and ether (500 mL) were added and the mixture was then warmed to room temperature. The organic layer was separated and the aqueous layer was further extracted with ether (200 mL). The combined organic layers were dried with anhydrous MgSO4, filtered through a silica gel pad and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using dichloromethane (100%) as eluent to afford 2,4-dichloropyrimidine-5-carbaldehyde (27.3 g, 71% yield) as a light yellow solid.1H NMR (400 MHz, CDCl3) δ 10.34 (s, 1H), 9.30 (s, 1H).
