反应详情

A solution of methyl 2-isocyanatobenzoate (10.00 g, 56.4 mmol) in tetrahydrofuran (30 ml) was slowly added to a solution of 4-(2-(trifluoromethyl)phenyl)piperidine hydrochloride (14.3 g, 53.8 mmol, Sigma) and triethylamine 99% (8.99 ml, 64.5 mmol) in tetrahydrofuran (120 ml) at 0° C. The mixture was removed from the cooling bath and stirred at room temperature for 15 min, at which time LC/MS analysis indicated that the reaction was complete. EtOH (75 ml) and aqueous LiOH (2N, 95 ml) were then added, and the solution was stirred for 6 h at room temperature. Subsequently, aqueous HCl (2N, 150 ml) was added, and the resulting mixture was extracted with EtOAc (2×600 ml). The EtOAc extract was dried over MgSO4 and concentrated to an off-white solid. Recrystallization from EtOAc yielded 14.0 g (66%) of 2-(4-(2-(trifluoromethyl)phenyl)piperidine-1-carboxamido) benzoic acid as a white solid, which was homogeneous by analytical high-performance liquid chromatography (>99%).

1. customThe mixture was removed from the cooling bath
2. additionEtOH (75 ml) and aqueous LiOH (2N, 95 ml) were then added
3. stirringthe solution was stirred for 6 h at room temperature
4. additionSubsequently, aqueous HCl (2N, 150 ml) was added
5. extractionthe resulting mixture was extracted with EtOAc (2×600 ml)
6. extractionThe EtOAc extract
7. dry with materialwas dried over MgSO4
8. concentrationconcentrated to an off-white solid
9. customRecrystallization from EtOAc