Piperazine → HCID 22720998, compound

Participants

Reaction Conditions

Reaction Steps

Phosgene (0.48 mL, 0.925 mmol, 1.93 M in toluene) was added dropwise to a mixture of triethylamine (0.14 mL, 1.0 mmol) and 4,5-bis-(4-chloro-phenyl)-2-(2-cyclopentyloxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazole (89 mg in THF (2 mL) at 0° C. The reaction mixture was stirred for 1 h at 0° C. and evaporated. The residue was kept under high vacuum for 30 min. Methylene chloride (2 mL) was added to the residue and the solution was added dropwise to a solution of piperazine (0.24 g, 2.78 mmol) in methylene chloride (2 mL) at 0° C. After 1 h, the reaction was worked up with aqueous sodium bicarbonate. The mixture was extracted with methylene chloride and washed with water and brine. The organic layer was extracted with 0.5 N HCl (2×50 mL). The combined aqueous layers were cooled to 0° C. and basified using 2 N NaOH. The mixture was extracted with methylene chloride (3×50 mL). The organic extracts were dried over sodium sulfate and evaporated. Flash chromatography of the residue over silica gel using 3-6% methanol in methylene chloride gave [4,5-Bis-(4-chloro-phenyl)-2-(2-cyclopentyloxy-4-methoxy-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (89 mg, 81%). HR-MS (ES, m/z) calculated for C32H35N4O3Cl2[(M+H)+]593.2081, observed 593.2084.

Provenance & Evidence