反应详情

温度

105 °C

Ethyl 3-(2,2-dimethylpropyl)-2-piperidin-1-ylcyclobutanecarboxylate (1470 g) and methyl p-toluenesulfonate (417 mL) were mixed. After the mixture was stirred at 105° C. for 2 hr, water (2100 mL) was poured into the reaction mixture and the aqueous layer was extracted. The aqueous layer was washed with tert-butyl methyl ether/hexane=1/1 (800 mL) and hexane (600 mL). To the aqueous layer was added potassium hydroxide (663 g) at ice temperature and the mixture was stirred at 100° C. for 2 hr. After the reaction mixture was washed with tert-butyl methyl ether/hexane=1/1 (600 mL×2), concentrated hydrochloric acid (500 mL) and 6 N hydrochloric acid (606 mL) were added to the aqueous layer at ice temperature. The mixture was extracted with ethyl acetate (600 mL×2). The combined organic layer was washed with water (1 L×2) and brine (500 mL), then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (278 g) as a crude product.

1. extractionthe aqueous layer was extracted
2. washThe aqueous layer was washed with tert-butyl methyl ether/hexane=1/1 (800 mL) and hexane (600 mL)
3. additionTo the aqueous layer was added potassium hydroxide (663 g) at ice temperature
4. stirringthe mixture was stirred at 100° C. for 2 hr
5. washAfter the reaction mixture was washed with tert-butyl methyl ether/hexane=1/1 (600 mL×2), concentrated hydrochloric acid (500 mL) and 6 N hydrochloric acid (606 mL)
6. additionwere added to the aqueous layer at ice temperature
7. extractionThe mixture was extracted with ethyl acetate (600 mL×2)
8. washThe combined organic layer was washed with water (1 L×2) and brine (500 mL)
9. dry with materialdried over magnesium sulfate
10. filtrationThe magnesium sulfate was filtered off
11. concentrationthe filtrate was concentrated in vacuo