反应详情

4-Fluoro-2-methyl-benzaldehyde (4 g) was added to a solution of 4-aminobutan-2-one ethylene acetal (3.8 g) in dry benzene (50 mL) and the solution was stirred at r.t. under a nitrogen atmosphere. After 1 hour the mixture was heated at reflux for 16 hours and then allowed to cool to r.t. This solution was slowly added to a refluxing solution of p-toluensulphonic acid (10.6 g) in dry benzene (50 mL) previously refluxed for 1 hour with a Dean-Stark apparatus. After 3.5 hours the crude solution was cooled and made basic with a saturated potassium carbonate solution and taken up with AcOEt (50 mL). The aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL). The organic layer was dried and concentrated in vacuo to a yellow thick oil as residue (7.23 g). A portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL) and stirred at 60° C. for 16 hours. The solution was basified with solid potassium carbonate and extracted with DCM (5×50 mL). The combined organic phases were washed with brine (50 mL), dried and concentrated in vacuo to give the title compound (2.5 g) as a thick yellow oil.

1. temperatureAfter 1 hour the mixture was heated
2. temperatureat reflux for 16 hours
3. temperatureto cool to r.t
4. temperaturepreviously refluxed for 1 hour with a Dean-Stark apparatus
5. extractionThe aqueous phase was extracted with AcOEt (3×50 mL) and Et2O (2×50 mL)
6. customThe organic layer was dried
7. concentrationconcentrated in vacuo to a yellow thick oil as residue (7.23 g)
8. dissolutionA portion of the crude mixture (3 g) was dissolved in a 6N hydrochloric acid solution (20 mL)
9. stirringstirred at 60° C. for 16 hours
10. extractionextracted with DCM (5×50 mL)
11. washThe combined organic phases were washed with brine (50 mL)
12. customdried
13. concentrationconcentrated in vacuo