反应详情

To a stirred solution of hydroxy-bis-(3-methoxy-phenyl)-acetic acid (Intermediate J) (1.384 g, 4.8 mmol) in dry THF (20 ml) is added CDI (0.870 g, 5.3 mmol) and the mixture is heated to reflux for 90 minutes. (R)-1-aza-bicyclo[2.2.2]octan-3-ol (0.67 g, 5.3 mmol) is then added. After refluxing for 16 hours, the reaction mixture is diluted with ethyl acetate and washed with water. The organic layer is then extracted with 2M HCl and the aqueous portion is treated with potassium carbonate to basify the solution. The aqueous portion is re-extracted with ethyl acetate. The organic portions are combined, dried over MgSO4 and concentrated in vacuo to yield a crude residue which is purified using C-18 reverse phase column chromatography (eluent: water-acetonitrile), to afford the titled compound.

1. temperaturethe mixture is heated
2. temperatureto reflux for 90 minutes
3. temperatureAfter refluxing for 16 hours
4. washwashed with water
5. extractionThe organic layer is then extracted with 2M HCl
6. additionthe aqueous portion is treated with potassium carbonate
7. extractionThe aqueous portion is re-extracted with ethyl acetate
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customto yield a crude residue which
11. customis purified