Ethylene Glycol → 2-(1-(3-Phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of (1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl 4-methylbenzenesulfonate (400 mg, 0.861 mmol), NaCN (127 mg, 2.58 mmol), and tetrabutylammoniumiodide (31.8 mg, 0.086 mmol) was stirred at 165° C. overnight. The reaction mixture was then cooled to rt and extracted with EtOAc (10 mL). The organic extract was washed with water and concentrated in vacuo. The residue was taken up with ethylene glycol (5 mL) and water (1 mL), and 40% aqueous KOH (1208 mg, 8.61 mmol) was added. The reaction was heated at 165° C. for 18 h. The mixture was concentrated in vacuo and the remaining solution was diluted with water and adjusted to pH 3 with conc. HCl. The mixture was extracted with EtOAc (2×5 mL). The combined organic layers were washed with water, dried (MgSO4), filtered, and concentrated in vacuo to afford the title compound (280 mg, 91% yield) as a white solid. LCMS, [M−H]+=337.0. 1H NMR (500 MHz, CDCl3) δ 7.38-7.27 (m, 3H), 7.19-7.08 (m, 3H), 7.03-6.99 (m, 2H), 6.87 (ddd, J=8.1, 2.4, 0.9 Hz, 1H), 3.97 (s, 2H), 2.23 (s, 2H), 2.17-2.00 (m, 4H), 1.95-1.79 (m, 4H).

Provenance & Evidence