Triphenylphosphine → Tert-butyl 3-(2-(4-bromo-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

4-Bromo-2-(trifluoromethyl)phenol (3 g), tert-butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate (2.81 g) and triphenylphosphine (3.92 g) were dissolved in DCM (25 ml). The reaction mixture was placed under a nitrogen atmosphere and cooled to 0° C. then DIAD (2.94 ml) was added dropwise. The mixture was stirred at room temperature for 16 hours then solvent evaporated under reduced pressure. The resulting residue was dissolved in ether (10 ml), heptane (15 mL) was then added and the suspension stirred for 45 minutes. The mixture was filtered (solid was washed with 3:2 heptane/ether) and the filtrate washed with NaOH (1M, 2×40 mL). Organics were dried over sodium sulphate and solvent evaporated under reduced pressure to yield crude product as a clear oil (6.05 g). Purification by flash chromatography (100 g silica column, 10% to 25% EtOAc in heptane gradient) afforded tert-butyl 3-(2-(4-bromo-2-(trifluoromethyl)phenoxy)ethyl)azetidine-1-carboxylate (52.6% yield) as a clear oil.

Provenance & Evidence