Sodium Hydroxide → HCID 90408389, compound

Participants

Reaction Steps

To a solution of 2-(1-(3-fluoro-5-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl) ethanol (350 mg, 1.00 mmol) in toluene (1 mL) was added Bu4NCl.H2O (89 mg, 0.300 mmol). The reaction mixture was cooled to 0° C. after which aqueous 35% NaOH (10 mL) and tert-butyl bromoacetate (295 μL, 1.99 mmol) were successively added. The reaction was stirred at rt for 18 h. The organic layer was separated, washed with H2O (5×15 mL) and brine (15 mL) until the pH=7, and then was concentrated in vacuo. The residual crude oil was purified by flash chromatography (SiO2) using a gradient from 0% to 30% EtOAc/hexane (10 min) to give the title compound (400 mg, 0.861 mmol, 86% yield) as a clear oil. 1H NMR (500 MHz, CDCl3) δ: 6.86 (t, J=1.7 Hz, 1H), 6.77-6.72 (m, 1H), 6.67 (d, J=10.5 Hz, 1H), 5.39 (s, 1H), 3.94 (s, 2H), 3.87 (s, 3H), 3.57 (t, J=6.9 Hz, 3H), 2.04-1.95 (m, 5H), 1.84 (d, J=5.0 Hz, 2H), 1.77-1.57 (m, 7H), 1.55-1.50 (m, 11H); 19F NMR (471 MHz, CDCl3) δ: −112.2 (s, 1F).

Provenance & Evidence