Dimethylformamide → 2-Chloro-3-methoxypyridine-4-carbaldehyde

To 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.

1. waitAfter a further 2.5 hours
2. customThe resultant biphasic mixture was separated
3. extractionextracted twice with diethyl ether
4. washThe combined organic phase was washed with water and brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-790a34942f874342ab6081ef51f374eb

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546376B2