Triethylamine → tert-Butyl 3-(azidomethyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a stirred solution of Part A N-Boc-3-hydroxymethylpiperidine (27.0 g, 126 mmol) in 150 mL of dry dichloromethane under argon at 0° C. was added in order triethylamine (22.7 mL, 163 mmol) and methanesulfonyl chloride (11.7 mL, 151 mmol). The reaction was stirred at room temperature for 1.5 h and diluted with 450 mL of dichloromethane. The reaction was washed with 0° C. 1N HCl solution (2×100 mL) and brine (1×100 mL). The dichloromethane layer was dried (Na2SO4), filtered and concentrated in vacuo. The residue was dissolved in 200 mL of DMF and combined with sodium azide (24.5 g, 377 mmol). The mixture was stirred at room temperature for 33 h and the solid was filtered off. The filtrate was concentrated under pump vacuum at 45° C. The residue was partitioned between 400 mL of EtOAc and 10% sodium thiosulfate solution (2×100 mL) and brine (1×100 mL). The EtOAc layer was dried (MgSO4), filtered and concentrated in vacuo. Purification was effected by a flash column chromatography on silica gel to give 19.5 g (65%) of title azide.

Provenance & Evidence