Dimethylformamide → 4-Chloro-5-fluoro-pyridine-3-carbaldehyde oxime

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Reaction Steps

To a cooled (−78° C.) solution of 3-fluoro-4-chloro-pyridine (11.0 g, 84 mmol) in THF under nitrogen was added lithium diisopropylamide (1.8 M solution, 47 mL, 84 mmol) dropwise and the resultant solution stirred at −70 to −80° C. for 18 hours. DMF (7.68 g, 1.25 eq.) was added dropwise and stirring continued at −78° C. for 30 minutes before adding the reaction mixture to ice/2M HCl. The solution was extracted with diethyl ether and the organic layer back-extracted with 2M HCl, the two aqueous solutions held separately. The aqueous extracts were each treated with hydroxylamine hydrochloride (8.76 g, 126 mmol) and adjusted to pH 5 with potassium carbonate. After stirring for 1 hour the mixtures were extracted with ethyl acetate (×2), the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a tan solid (11.07 g, 76%). LCMS (method B): RT=2.49 min, M+H+ 175.

Provenance & Evidence