Br[C:2]1[C:3]([Cl:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.N1(C=O)CC[O:13][CH2:12]C1.Cl.CCOCC>C1COCC1>[Cl:8][C:5]1[N:4]=[C:3]([Cl:9])[C:2]([CH:12]=[O:13])=[CH:7][N:6]=1A solution of isopropyl magnesium chloride lithium chloride complex in THF (2M, 184 mL, 368 mmol) was added drop-wise over about 30 min to a 2 L round-bottomed flask charged with a solution of 5-bromo-2,4-dichloropyrimidine (49.6 g, 218 mmol) in THF (1000 mL) at about −78° C. The reaction was allowed to stir at about −78° C. for about 30 min. Morpholine-4-carbaldehyde (75.0 g, 653 mmol) was then added drop-wise at about −78° C. over about 30 min. The reaction was allowed to stir for about 30 min at about −78° C. then allowed to warm to about −35° C. and stirred for about 30 min. Aqueous HCl (1N, 250 mL) and Et2O (500 mL) were added and the reaction mixture was allowed to warm to ambient temperature. The organic layer was separated and the aqueous layer was further extracted with Et2O (200 mL). The combined organic layers were dried over anhydrous MgSO4, filtered through a silica gel pad on a fritted funnel, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography using DCM (100%) as the eluent to provide 2,4-dichloropyrimidine-5-carbaldehyde (27.3 g, 71%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.34 (s, 1H), 9.30 (s, 1H).
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