Dimethylformamide → 2-Chloro-3-methoxypyridine-4-carbaldehyde
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[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.CN([CH:18]=[O:19])C.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH:18]=[O:19])[CH:5]=[CH:4][N:3]=1[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.CN([CH:18]=[O:19])C.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH:18]=[O:19])[CH:5]=[CH:4][N:3]=1To a stirred solution of 2-chloro-3-methoxypyridine (1.55 g, 10.8 mmol, prepared as described in WO2007/123995) in dry THF (30 mL), cooled to −78° C., was added 2.5 M nBuLi in hexanes (4.75 mL, 11.9 mmol). After 1 hour, a solution of DMF (2.5 mL, 32.4 mmol) in THF (5 mL) was added. After a further 2.5 hours, a saturated aqueous ammonium chloride solution was added and the reaction mixture was allowed to warm to RT. The resultant biphasic mixture was separated and extracted twice with diethyl ether. The combined organic phase was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 20 to 25% ethyl acetate in cyclohexane) to afford the title compound (1.42 g, 77%) as a white solid. 1H NMR (300 MHz, CDCl3): δ 10.44 (d, J=0.8 Hz, 1H), 8.34 (dd, J=4.9 and 0.8 Hz, 1H), 7.60 (d, J=4.9 Hz, 1H), 4.08 (s, 3H). LCMS (Method A): RT=2.84 min, [M+H]+=172/174.
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