反应详情

In a three-necked flask equipped with a Dean-Stark apparatus, heating mantle and magnetic stirrer were charged 1-benzyl-7-methoxy-3,4-dihydronaphthalen-2(1H)-one (120 g, 451 mmol), propionamide (82 g, 1126 mmol) and p-toluenesulfonic acid monohydrate (17.14 g, 90 mmol) followed by toluene (1.8 I). The resulting solution was heated to reflux for 5 days and monitored by HPLC (about 16% of starting material remained). The reaction mixture was cooled to r.t. and washed with 8% aqueous sodium bicarbonate solution (250 ml) and water (250 ml). The layers were separated. The organic layer was concentrated to near dryness and chase distilled with IPA (100 ml). The crude product was transferred to a flask equipped with a mechanical stirrer, heating mantle and nitrogen inlet. IPA (500 ml) was added to the flask and suspension was heated to 62° C. and all the solids were dissolved. The suspension was allowed to cool over 2 hrs to 30° C. then cooled to 5° C. Solids were filtered and washed with mixture of heptane/IPA (4:1, 100 ml). Solids were dried under vacuum to give 93.5 g (yield: 65%) product as a white solid.

1. customIn a three-necked flask equipped with a Dean-Stark apparatus
2. temperatureheating mantle
3. temperatureThe resulting solution was heated
4. temperatureto reflux for 5 days
5. washwashed with 8% aqueous sodium bicarbonate solution (250 ml) and water (250 ml)
6. customThe layers were separated
7. concentrationThe organic layer was concentrated
8. distillationchase distilled with IPA (100 ml)
9. customThe crude product was transferred to a flask
10. customequipped with a mechanical stirrer
11. temperatureheating mantle
12. additionIPA (500 ml) was added to the flask and suspension
13. temperaturewas heated to 62° C.
14. dissolutionall the solids were dissolved
15. temperatureto cool over 2 hrs to 30° C.
16. temperaturethen cooled to 5° C
17. filtrationSolids were filtered
18. washwashed with mixture of heptane/IPA (4:1, 100 ml)
19. customSolids were dried under vacuum