Triphenylphosphine → tert-Butyl (3R)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (5 g, 26.7 mmol), 2-(trifluoromethyl)phenol (4.8 h, 29.4 mmol) and triphenylphosphine (8.4 g, 32 mmol) in THF (75 mL) at rt was added DEAD (5.1 mL, 32 mmol) over 5-10 min. The mixture was stirred at rt for 2 days. Solvent was evaporated. The residue was diluted with EtOAc and washed successively with 1 N aqueous NaOH and brine. The EtOAc layer was separated, dried (Na2SO4) and concentrated. Chromatography over silica gel and elution with hexanes/EtOAc (10:1, then 3:1) gave tert-butyl (3R)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine-1-carboxylate as a colorless oil, which solidified on standing. 1H NMR (500 MHz, acetone-d6): δ 7.63 (m, 2 H), 7.31 (d, 1 H), 7.13 (t, 1 H), 5.26 (s, 1 H), 3.68-3.43 (m, 4 H), 2.21 (m, 2 H), 1.45 (s, 9 H).

Provenance & Evidence