反应详情

温度

95 °C

To two 125 mL 3 neck flasks with mechanical stirring, condensers, and a heating apparatus consisting of an RTD probe in the flask hooked via a temperature controller to a heating mantle the following were added: 7.61 g of methyl 4-hydroxybenzoate, 11.05 g of β-chloroethylpiperidine hydrochloride, 16.59 g of powdered potassium carbonate, and 60 mL of amyl acetate. The flasks were placed in an ambient oil bath and heated under nitrogen to 95° C.-100° C. The reaction was allowed to proceed until HPLC indicated 8% unreacted methyl 4-hydroxybenzoate in A, 12% unreacted in B. The flasks were then cooled to less than 50° C. 40 mL deionized water was added with stirring to dissolve solids. The aqueous layer was separated and discarded. The water wash was repeated and the aqueous layer was separated and discarded. HPLC of organic layers showed 6% 4-hydroxybenzoate remains in A, 3% in B. 25 mL of 8N hydrochloric acid was added with stirring to extract the intermediate. The layers were separated and the acid layers returned to reaction flasks. The acid solutions were heated at about 95° C. for about 4 hours. The flasks were then cooled to less than 40° C. and 25 mL of acetone was added. The mixture was then cooled to 0° C.-5° C. for 1 hour. The mixture was filtered and the cakes rinsed with approximately 25 mL of acetone and dried. A=11.50 g (80.5%), B=10.5 g (73.8%)

1. additionwere added
2. customThe flasks were placed in an ambient oil bath
3. temperatureheated under nitrogen to 95° C.-100° C
4. temperatureThe flasks were then cooled to less than 50° C
5. additionwas added
6. dissolutionto dissolve solids
7. customThe aqueous layer was separated
8. washThe water wash
9. customthe aqueous layer was separated
10. addition25 mL of 8N hydrochloric acid was added
11. stirringwith stirring
12. extractionto extract the intermediate
13. customThe layers were separated
14. customthe acid layers returned to reaction flasks
15. temperatureThe flasks were then cooled to less than 40° C.
16. temperatureThe mixture was then cooled to 0° C.-5° C. for 1 hour
17. filtrationThe mixture was filtered
18. washthe cakes rinsed with approximately 25 mL of acetone
19. customdried