反应详情

温度

0 °C

3-Bromo-2,2-dimethylpropionic acid (1.50 g, 8.29 mmol) was dissolved in thionyl chloride (10 mL) and DMF (0.1 mL). The reaction mixture was heated at reflux for 1.5 hours and then concentrated in vacuo, The residue was dissolved in DCM (10 mL) and added to a solution of 4-chlorophenyl piperazine dihydrochloride (2.35 g, 8.70 mmol) and DIPEA (5.05 mL, 29.0 mmol) in DCM (20 mL) at 0° C. The reaction mixture was stirred at 0° C. for 2 hours and then concentrated in vacuo. The residue was dissolved in DCM (100 mL) and washed with 10% citric acid solution (50 mL), sat aq NaHCO3 solution (50 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The resulting residue was purified using normal phase column chromatography (eluting with heptane, followed by a 1:1 mixture of EtOAc:heptane) to give 3-bromo-1-(4-chlorophenyl)piperazine-2,2-dimethyl-propan-1-one (0.87 g, 29.3%) as a yellow solid.

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 1.5 hours
3. concentrationconcentrated in vacuo
4. dissolutionThe residue was dissolved in DCM (10 mL)
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in DCM (100 mL)
7. washwashed with 10% citric acid solution (50 mL)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customThe resulting residue was purified
11. washeluting with heptane
12. additionfollowed by a 1:1 mixture of EtOAc