Sodium hydride → tert-Butyl 4-((5-nitropyridin-2-yl)oxy)piperidine-1-carboxylate

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Reaction Steps

Add a suspension of pre-washed NaH (0.1 g, 2.48 mmol, 60% dispersion in mineral oil) in THF (2 mL) to an ice cold solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 2.48 mmol) in dry THF (3 mL). Allow mixture to stir for 20 minutes, then add 2-chloro-5-nitro-pyridine (0.36 g, 2.26 mmol) in portions. After addition is completed, remove cooling bath and stir the reaction mixture at 22° C. overnight. Cool reaction mixture with ice bath and add a saturated aq. sodium bicarbonate solution (5 mL). Distribute the reaction mixture between ethyl acetate (25 mL) and distilled water (25 mL). Isolate the aqueous phase and extract with ethyl acetate (3×35 mL). Dry the combined organic phases over sodium sulfate and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with hexanes and ethyl acetate to give 4-(5-Nitro-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (0.55 g, 75% yield). MS(ES): m/z=324.2 [M+H].

Provenance & Evidence