3-(Chloromethyl)pyridine hydrochloride → 3-((3-Fluoro-4-nitrophenoxy)methyl)pyridine

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Reaction Steps

3-Fluoro-4-nitrophenol (7.5 g) is added to a stirred suspension of sodium hydride (2.2 g, 60% dispersion in mineral oil) in DMF (50 mL). The mixture is stirred at ambient temperature for 30 minutes. To this mixture is added a solution prepared by the addition of sodium hydride (2.2 g, 60% dispersion in mineral oil) to a stirred suspension of 3-chloromethylpyridine hydrochloride (8.2 g) in DMF (50 mL). The resulting mixture is stirred at 90° C. for 16 hours then cooled to ambient temperature. The reaction mixture is concentrated in vacuo and the residue partitioned between dichloromethane (100 mL) and water (100 mL). The aqueous phase is extracted four times with dichloromethane (100 mL). The combined organic phases are washed with brine (100 mL), dried over magnesium sulphate, filtered and concentrated in vacuo to give an orange solid. Recrystallisation from ethyl acetate gives 3-(3-fluoro-4-nitrophenoxymethyl)pyridine (4.6 g) as pale orange/brown cystals.

Provenance & Evidence