反应详情

温度

80 °C

To an ice cooled and stirred solution of 4-(4-aminophenyl)piperazine (4.29 g, 24.2 mmol) in dichloromethane (100 mL) containing Et3N (7.42 mL, 52.5 mmol) was added trifluoroacetic anhydride (7.52 mL, 53.2 mmol) in dichloromethane (25 mL) over a 5 minute period. The mixture was allowed to warm to room temperature and stirred two days, then stirred with ice water. The pink solid that separated was isolated by filtration, washed with dichloromethane, aqueous sodium bicarbonate, and water, and dried to obtain 1-(4-(trifluoroacetamido)phenyl)-4-trifluoroacetylpiperazine (4.09 g, 46% , mp 193°-194° C.). To a mixture of this material (0.37 g, 1 mmol ) and anhydrous potassium carbonate (1.1 g, 8.0 mmol) in acetonitrile (50 mL) was added 3,3,3-triphenylpropionyl chloride (0.54 g) and the mixture stirred at 80° C. for two days. With tlc monitoring, four additional lots of the acid chloride (4×0.54 g) and potassium carbonate (4×1.1 g) were added at 3 hr intervals, with continued reflux until complete disappearance of the starting piperazine by tlc. The solvent was removed in vacuo, the residue triturated with methanol, the solids removed by filtration and the filtrate evaporated to dryness in vacuo. The residue was stirred with 20% KOH in methanol (15 mL) for 3 hr and then evaporated to dryness in vacuo. The residue was partitioned between water and ethyl acetate and the organic layer extracted with 2N HCl. The acid extract was basified with 2N NaOH to pH 9.5 and extracted with ethyl acetate. The organic layer was washed with brine, then dried over sodium sulfate and evaporated to dryness to give the title compound as a tan solid (0.40 g, 87%), mp 193°-195° C. 1H NMR (CDCl3) δ 7.33 (m,15H), 6.89 (d, J=8.9, 2H) 6.73 (d, J=8.9, 2H), 6.26 (s, 1H), 3.70 (s, 2H), 3.00 (d, J=10.0, 8H). IR 3056, 1665, 1598, 1515, 1447, 1239, 700 cm-1. MS 462 (MH+). Anal. calcd. for: C31H31N3O·0.5 H2O: C, 79.12; H, 6.85; N, 8.93. Found: C, 78.84; H, 6.66; N, 8.64.

1. customThe solvent was removed in vacuo
2. customthe residue triturated with methanol
3. customthe solids removed by filtration
4. customthe filtrate evaporated to dryness in vacuo
5. stirringThe residue was stirred with 20% KOH in methanol (15 mL) for 3 hr
6. customevaporated to dryness in vacuo
7. customThe residue was partitioned between water and ethyl acetate
8. extractionthe organic layer extracted with 2N HCl
9. extractionThe acid extract
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with brine
12. dry with materialdried over sodium sulfate
13. customevaporated to dryness