反应详情

Under nitrogen, a solution of 4-(4-bromo-phenyl)-4-(4-chloro-phenyl)piperidine-1-carboxylic acid tert-butyl ester* (888 mg, 1.97 mmol) in THF (5 mL) was cooled to −78° C. A solution of n-butyllithium (1.5 mL, 1.6M in hexanes) was added dropwise and the mixture maintained at this temperature for 25 minutes. Carbon dioxide gas (generated from dry ice and dried by passage through a column of calcium chloride pellets) was bubbled through the anion solution for 80 minutes then the mixture was allowed to warm to room temperature. The solvents were removed in vacuo then the residue was partitioned between 1N hydrochloric acid and diethyl ether. The organic phase was separated, dried (MgSO4), filtered and concentrated. The combined aqueous phases were further extracted with ethyl acetate, this extract also being dried (MgSO4), filtered, combined with the ethereal extract and concentrated to afford 4-(4-carboxy-phenyl)-4-(4-chloro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (889 mg); LCMS (PS-A2) Rt 3.52 min [M-tBu+H]+ 360.

1. temperaturethe mixture maintained at this temperature for 25 minutes
2. dry with materialdried by passage through a column of calcium chloride pellets)
3. customwas bubbled through the anion solution for 80 minutes
4. customThe solvents were removed in vacuo
5. customthe residue was partitioned between 1N hydrochloric acid and diethyl ether
6. customThe organic phase was separated
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. extractionThe combined aqueous phases were further extracted with ethyl acetate
11. extractionthis extract also
12. dry with materialbeing dried (MgSO4)
13. filtrationfiltered
14. extractionextract
15. concentrationconcentrated