反应详情

温度

150 °C

A suspension of 1-((4-chlorophenyl)phenylmethyl)piperazine (260 g, 0.9 mol), tert-butyl 2-(2-chloroethoxy)acetate (195 g, 1.0 mol), sodium hydroxide (106 g, 1 mol) and tert-butyl-ammonium bromide (“TABB”, 3.22 g, 0.01 mol, NOTE-TABB is a catalyst for this reaction) is dissolved in 2-butanone (“MEK”, 300 mL) heated to 150° C. and the water of reaction azeotroped over a period of about 4 hours. Heating is stopped and to the reaction mixture is added MEK (500 mL) added. The mixture is cooled to ambient, filtered and the solvent removed from the resulting solution by distillation under reduced pressure. The residue is dissolved in methyl tert-butylether (800 mL), washed with water (2×200 mL), saturated sodium chloride (2×100 mL) and the solvent removed under reduced pressure. The residue is treated with hexanes (1.8 mL) to afford tert-butyl (RS) 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetate as a white crystalline powder (260 g, 96% yield).

1. customfor this reaction)
2. customazeotroped over a period of about 4 hours
3. temperatureHeating
4. additionis added MEK (500 mL)
5. additionadded
6. temperatureThe mixture is cooled to ambient,
7. filtrationfiltered
8. customthe solvent removed from the resulting solution by distillation under reduced pressure
9. dissolutionThe residue is dissolved in methyl tert-butylether (800 mL)
10. washwashed with water (2×200 mL), saturated sodium chloride (2×100 mL)
11. customthe solvent removed under reduced pressure
12. additionThe residue is treated with hexanes (1.8 mL)