CN1CCNCC1.C([Li])CCC.[CH3:13][O:14][C:15]1[N:20]=[C:19]([CH:21]=[O:22])[CH:18]=[CH:17][CH:16]=1.C([Li])(C)(C)C.[Cl:28]C(Cl)(Cl)C(Cl)(Cl)Cl>O1CCCC1.O>[Cl:28][C:16]1[CH:17]=[CH:18][C:19]([CH:21]=[O:22])=[N:20][C:15]=1[O:14][CH3:13]A solution of methylpiperazine (2.31 g) in tetrahydrofuran (20 mL) was cooled to −78° C., and n-butyllithium (2.64 M, 7.55 mL) was added dropwise in an argon gas atmosphere. After stirring at the same temperature for 15 minutes, a solution of 6-methoxypicolinaldehyde (2.5 g) in tetrahydrofuran was added and the mixture was stirred for 30 minutes. t-Butyllithium (1.59 M, 17.1 mL) was added dropwise to the reaction solution, and the mixture was stirred at the same temperature for one hour and at −40° C. for 15 minutes. The reaction solution was cooled again to −78° C. A solution of hexachloroethane (12.9 g) in tetrahydrofuran (20 mL) was slowly added dropwise, and the mixture was stirred at the same temperature for 30 minutes. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered, after which the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1→10:1) to give 5-chloro-6-methoxypyridine-2-carbaldehyde as a colorless powder (1.21 g).
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