Hydrochloric Acid → (5-Fluoro-2-methoxyphenyl)(3'-fluoro-4-methyl-3,4'-bipyridin-2'-yl)methanone

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Reaction Steps

To a solution of 3′-fluoro-4-methyl-3,4′-bipyridine-2′-carbonitrile (0.031 g, 0.145 mmol) in THF (Volume: 0.727 ml) cooled to 0° C. was added (5-fluoro-2-methoxyphenyl)magnesium bromide (0.727 ml, 0.363 mmol). The reaction mixture was allowed to stir at room temperature. Water and ice were carefully added, followed by acidification with 6 M HCl. After stirring for 1 hr, CH2Cl2 was added and the pH was adjusted to 8.5 with aqueous 4 M NaOH. The layers were separated. The aqueous phase was extracted with CH2Cl2 (5×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford a purple residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (4 g column, 18 mL/min, 60-100% EtOAc in hexanes over 18 min, tr=9 min) gave the title compound (0.024 g, 0.070 mmol, 48.0% yield) as an orange residue. ESI MS (M+H)+=340.2.

Provenance & Evidence