Ethyl Acetate → (3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (15.5 mmol, 3.1 g) in DMF (25 mL) was added a solution of sodium azide (23.3 mmol, 1.5 g) in acetone-water (2:1, 30 mL) (WO 2005/066176). The reaction mixture was heated at 80° C. for 12 h. The reaction mixture was cooled to room temperature, and EtOAc (100 mL) was added. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a SiO2 cartridge (5% EtOAc in hexane-25% EtOAc in hexane) to provide (±)-trans-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (2.3 g) (faster moving compound) 1H NMR (400 MHz, CDCl3) δ 4.12 (1 H, dd), 3.95 (1 H, bs), 3.50 (1 H, bs), 3.30-3.42 (1 H, m), 2.90 (1 H, bs), 2.79 (1 H, dd), 2.30-2.70 (1 H, bs), 1.96-2.05 (1 H, m), 1.48-1.6 (1 H, m), 1.46 (9 H, s). and (±)-trans-3-azido-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.57 g) (slower moving compound) 1H NMR (400 MHz, CDCl3) δ 4.21 (1 H, bs), 4.00 (1 H, d), 3.56 (1 H, bs), 3.21-3.35 (1 H, m), 2.55-2.95 (2 H, m), 2.24 (1 H, bs), 1.92-2.04 (1 H, m), 1.49-1.6 (1 H, m), 1.47 (9 H, s)

Provenance & Evidence