Dimethyl Sulfoxide → N,N'-Dicyclohexylurea

Participants

Reaction Conditions

Reaction Steps

In a 200 mL round-bottomed flask, ethyl 4-(4-hydroxypiperidin-1-yl)benzoate 390A (0.878 g, 3.52 mmol), DCC (2.202 g, 10.67 mmol), and DMSO (5.0 mL, 70.5 mmol) were taken up in benzene (9.52 mL) to give a colorless solution. The mixture was then cooled in an ice/brine bath. Pyridine (0.26 mL, 3.21 mmol) and TFA (0.12 mL, 1.558 mmol) were added sequentially and in a drop-wise manner, while maintaining the reaction mixture at <5° C. Once the additions were complete, the reaction was allowed to stir at the cooler temperature and then slowly warmed to 23° C. over a 24 hr period. The reaction was diluted with EtOAc (50 mL) and stirred at 23° C. overnight. The undissolved white solid (dicyclohexylurea) was removed by filtration and rinsed with additional EtOAc. The organic layer was washed with brine, dried with MgSO4, filtered, and concentrated to clear oil. The oil was triturated with hexanes and gently stirred overnight. A white solid was collected by filtration and dried in vacuo. Re-crystallization in CCl4 gave a fine solid (dicyclohexylurea impurity) that was removed by vacuum filtration. The CCl4 filtrate was concentrated to yellow oil and dried in vacuo to afford the title compound as a yellow solid (0.575 g, 66.0% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (t, J=7.07 Hz, 3H) 2.45 (t, J=6.06 Hz, 4H) 3.74 (t, J=6.06 Hz, 4H) 4.24 (q, J=7.07 Hz, 2H) 6.97-7.09 (m, 2H) 7.75-7.86 (m, 2H). ESI-MS: m/z 248.2 (M+H)+.

Provenance & Evidence