Sodium hydride → HCID 68538403, compound

Participants

Reaction Steps

Add a suspension of pre-washed NaH (1.27 g, 31.87 mmol, 60% dispersion in mineral oil) in THF (20 mL) to an ice cold solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (6.41 g, 31.87 mmol) in dry THF (80 mL). Allow the mixture to stir for 20 minutes, then add 2-chloro-3-methyl-5-nitro pyridine (5 g, 28.97 mmol) in portions. After addition is completed, remove cooling bath and stir the reaction mixture at 22° C. overnight. Cool the reaction mixture with an ice bath and add a saturated aq. sodium bicarbonate solution (50 mL). Distribute the reaction mixture between ethyl acetate (350 mL) and distilled water (150 mL). Isolate the aqueous phase and extract with ethyl acetate (1×100 mL). Combine organic layers and wash with saturated aq. sodium chloride solution (2×150 mL). Dry the combined organic phases over sodium sulfate and concentrate. Subject residue to silica gel chromatography eluting with hexanes and ethyl acetate to give 4-(3-methyl-5-nitro-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (6.5 g, 67% yield). MS(ES): m/z=360.3 [M+Na].

Provenance & Evidence