2-Chloro-4-(4-methoxyphenyl)pyridine → 4-(4-Methoxyphenyl)-2-methylpyridine

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Reaction Steps

A mixture of 2-chloro-4-(4-methoxyphenyl)pyridine (660 mg) and bis(triphenyl-phosphine)nickeldichloride (200 mg) in anhydrous tetrahydrofuran (7.5 mL) is cooled to a temperature close to 0° C. A solution of methylmagnesiumbromide in tetrahydrofuran (2.6 M, 2 mL) is added slowly. The mixture is stirred at room temperature for two hours, concentrated under reduced pressure and dissolved in methyl tert-butyl ether (10 mL). Alkaloids are extracted with a 3N aqueous solution of hydrochloric acid (3 times 10 mL). Extracts are pooled, alkalinised and back extracted with methyl tert-butyl ether (3 times 20 mL) and dichloromethane (30 mL). Organic phases are dried over magnesium sulphate, concentrated under reduced pressure and purified over silica gel (eluent dichloromethane/methanol from 100/0 to 95/5). Fraction containing the expected product are pooled and concentrated under reduced pressure to give 385 mg of 4-(4-methoxyphenyl)-2-methylpyridine as a clear brown powder used without further purification.

Provenance & Evidence