Ammonium Chloride → tert-Butyl 4-azido-3-hydroxypiperidine-1-carboxylate

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Reaction Conditions

Reaction Steps

Sodium azide (0.94 g, 14.2 mmol) was added to a suspension of 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylic acid 1,1-dimethylethyl ester (2.18 g, 10.9 mmol) and ammonium chloride (0.76 g, 14.2 mmol) in a mixture of EtOH (11 mL) and H2O (11 mL). The mixture was stirred at 150° C. for 5 minutes under microwave irradiation. Then a saturated solution of NaHCO3 was added and the mixture was extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in Heptane 20/80 to 80/20). The desired fractions were collected and the solvents evaporated in vacuo to yield 4-azido-3-hydroxy-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (0.93 g, 35% yield) and 3-azido-4-hydroxy-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (0.26 g, 10% yield).

Provenance & Evidence