反应详情

温度

165 °C

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).

1. temperatureThe reaction mixture was then cooled to rt
2. extractionextracted with EtOAc (10 mL)
3. extractionThe organic extract
4. washwas washed with water
5. concentrationconcentrated in vacuo
6. additionwas added
7. temperatureThe reaction was heated at 165° C. for 18 h
8. concentrationThe mixture was concentrated in vacuo
9. additionthe remaining solution was diluted with water
10. extractionThe mixture was extracted with EtOAc (2×5 mL)
11. washThe combined organic layers were washed with water
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo